Jahresbericht MOH 2022-2023

Klinik für Medizinische Onkologie und Hämatologie

Jahresbericht 2022/2023

Impressum

Herausgeber

Klinik für Medizinische Onkologie und Hämatologie (MOH) Universitätsspital Zürich Rämistrasse 100 8091 Zürich www.usz.ch/moh

Redaktion

Markus G. Manz, Prof. Dr. med. Maja Zenz, PhD

Gestaltung info@klauserdesign.ch

Fotos

Nicolas Zonvi

Druck

N&E Print, Siebnen

Auflage

500 Expl.

Stand

Juni 2024

Prof. Dr. med. Markus G. Manz

Klinikdirektor

Medizinische Onkologie und Hämatologie (MOH)

Lehrstuhl Hämatologie

Universität Zürich (UZH)

Chair Comprehensive Cancer Center Zürich (CCCZ)

Ich freue mich, Ihnen den 2-Jahresbericht für die Jahre 2022/2023 der Klinik für Medizinische Onkologie und Hämatologie (MOH) am Universitätsspital Zürich (USZ) vorzustellen. Dies ist der zweite Bericht der MOH in dieser Form. Im ersten Bericht (2021/2022) haben wir gesamthaft unsere Strukturen und Aktivitäten in den Bereichen Patientenversorgung, Forschung und Lehre vorgestellt (www.usz.ch/moh).

Als universitäre Klinik haben wir den Anspruch die Präventions-, Diagnoseund Behandlungsmöglichkeiten für unsere Patient:innen kontinuierlich zu verbessern. Im aktuellen Bericht möchten wir unsere neuen Projekte und Initiativen in der Forschung hervorheben. Unsere wissenschaftlichen Schwerpunkte sind die molekulare Präzisionsonkologie, Immuntherapien und zelluläre Therapien. In diesen Bereichen entwickeln wir interdisziplinäre Programme, die Krebsmedizin und Krebsforschung verbinden. So ermöglichen wir unseren Patient:innen individualisierte Behandlungskonzepte, getrieben durch aktive Innovationsleistung in Zürich.

Unter Federführung der MOH neu gestartete Krebsforschungsprogramme sind unter anderen das CCCZ Leuchtturmprojekt ZURICAR, welches darauf abzielt, innovative Plattformen für die effektive, flexible, sichere und kosteneffiziente Produktion von Chimeric Antigen Receptor (CAR)-Immunzellen zu entwickeln. Die klinische Studie RAPID untersucht, ob die Behandlung der rezidivierten akuten myeloischen Leukämie durch Pharmakoskopie – eine funktionelle Plattform für Präzisionsmedizin – optimiert werden kann. Lesen Sie mehr zu unseren Forschungsnetzwerken in Kapitel 10. In Kapitel 11 stellen sich unsere Forschungsgruppen mit Ergebnissen aus den letzten beiden Jahren vor.

Wie auch im letzten Bericht geben Kapitel 7 und 8 einen Überblick über unsere Leistung(szahlen) in der Patientenversorgung und Diagnostik.

Die Jahre 2022–2023 waren für die MOH «Jahre der Evaluation». So wurde die MOH durch die UZH in den Bereichen Strukturen, Forschung, Lehre und akademische Weiterbildung begutachtet. Das externe Expertengremium bewertete die diagnostischen Verfahren und Technologien als umfassend, die Grundlagenforschung in der Hämatologie als exzellent und die Lehre für Medizinstudenten in der Hämatologie als hervorragend. Als Empfehlungen wurden unter anderem ausgesprochen, die strukturellen Bedingungen für klinische Studien sowie die solide Tumoronkologie in der MOH und gesamthaft am CCCZ zu stärken.

Das CCCZ wurde im Jahr 2023 zum ersten Mal durch seinen externen wissenschaftlichen Beirat evaluiert. Auf Basis eines 130-seitigen Statusberichts sowie über 30 Vorträgen von Ärzt:innen und Wissenschaftler:innen des CCCZ

kam der wissenschaftliche Beirat zu folgendem zusammenfassenden Evaluierungsbeschluss: «Die interdisziplinäre Organisation der Patientenversorgung und die innovativen Krebsforschungsprogramme des CCCZ erfüllen die Standards eines onkologischen Exzellenzzentrums nach internationalen Kriterien». Wir sind stolz, dass unsere Klinik die kontinuierliche Entwicklung eines führenden Comprehensive Cancer Centers am Standort Zürich vorantreiben und unterstützen kann.

Grundlage und Nährboden für all diese Leistungen und Erfolge sind unsere MOH Mitarbeiter:innen. Mein Dank geht an das persönliche Engagement jedes einzelnen Mitarbeitenden – in einem Umfeld, das viel verlangt und sich rasant weiterentwickelt – für unser gemeinsames Ziel, Patient:innen eine moderne und ganzheitliche Medizin auf höchstem Niveau zu bieten.

Ich wünsche viel Freude beim Lesen.

Markus G. Manz

Wir bieten Patient:innen mit Tumorerkrankungen, Bluterkrankungen und Gerinnungsstörungen eine ganzheitliche und fachübergreifende Medizin auf höchstem Niveau.

Wir erforschen und entwickeln innovative diagnostische und therapeutische Konzepte. Gemeinsam arbeiten wir daran, die Entstehung und Pathobiologie von Erkrankungen besser zu verstehen und Patient:innen individualisiert noch effektiver behandeln zu können.

Wir engagieren uns in der Aus- und Weiterbildung von Ärzt:innen und Wissenschaftler:innen und fördern die fachliche und persönliche Entwicklung aller unserer Mitarbeitenden.

Unser Umgang ist geprägt von Respekt sowie einer offenen und transparenten Kommunikation. Verantwortlichkeiten und Aufgaben in unserer Klinik sind klar strukturiert und ermöglichen eine effiziente und vertrauensvolle Zusammenarbeit.

Übersicht 3

Die Klinik für Medizinische Onkologie und Hämatologie (MOH) bietet für Patient:innen mit Krebserkrankungen aller Organsysteme, gutartigen Bluterkrankungen und Gerinnungsstörungen eine ganzheitliche medizinische Versorgung nach höchsten Standards.

Die MOH umfasst die Bereiche für Medizinische Onkologie und Hämatologie am USZ und ist ein integraler Bestandteil des Comprehensive Cancer Center Zürich (CCCZ).

In unserer Klinik arbeiten rund 390 Mitarbeitende: >70 Ärzt:innen (MOH), >175 Pflegende (USZ Pflege/MTTB), >50 Mitarbeitende aus dem Bereich Medizin/Labortechnik (USZ MTTB), >70 Mitarbeitende aus den Bereichen Forschung & Studienmanagement (MOH) sowie >25 Mitarbeitende aus den Bereichen Dokumentation, Disposition und Administration (MOH).

In unseren Ambulatorien im Zentrum und am Flughafen verzeichnen wir pro Jahr >53.000 Patientenbesuche (2022: 53.448/2023: 53.649).

In unserer Tagesklinik führen wir pro Jahr >13.500 ambulante Therapien durch (2022: 13.627/ 2023: 14.014).

Wir betreuen täglich rund 50 stationäre Patient:innen, davon circa 16 auf unserer hochspezialisierten Station für zelluläre Therapien. In den Jahren 2022/2023 verzeichneten wir 1.839/1.689 Patientenaustritte.

Wir decken den gesamten Routine- und Spezialbereich der zellulären, molekularen hämatologischen und gerinnungsphysiologischen Diagnostik am USZ im 24h Betrieb ab. Jährlich werden in der hämatologischen Diagnostik >400.000 Laboranalysen durchgeführt. In der wöchentlichen hämato-pathologischen Konferenz werden die Diagnosen fachübergreifend mit dem Institut für Pathologie abgeglichen.

Das immunhämatologische Labor und die Transfusionsmedizin der MOH führen immunhämatologische Abklärungen durch und stellen zu jeder Zeit für das gesamte USZ Blutprodukte bereit, die auch vom Blutspendedienst Zürich bezogen werden. Jährlich werden am USZ >2.500 spezialisierte Antikörperabklärungen durchgeführt und >24.000 Blutprodukte ausgegeben.

In den Jahren 2022/2023 wurden in der Apherese-Einheit der MOH 37/52 unverwandte, 30/33 verwandte und 130/128 autologe Blutstammzell-Sammlungen durchgeführt. Die Anzahl der Lymphapheresen zur CAR T-Zelltherapie betrug 34/34 und die Gesamtzahl der stationären und ambulanten Plasmaaustauschtherapien 516/594. Es wurden 95/86 autologe und 67/85 allogene Blutstammzelltransplantationen sowie 32/29 CAR T-Zelltherapien durchgeführt.

Das MOH Biobanking und CCCZ Sample Processing Lab kümmern sich um die standardisierte Verarbeitung und Lagerung von Gewebe- und Blutproben für Forschungszwecke. Pro Jahr werden >1.400 Proben asserviert.

Durch unsere Grundlagen- und klinische Forschung sind wir als universitäre Institution kontinuierlich bemüht, die Medizin in allen Aspekten weiter zu verbessern. In den Jahren 2022/2023 haben wir >80 klinische Studien durchgeführt und konnten so unseren Patient:innen neue, innovative Therapieansätze anbieten.

In der MOH arbeiten 13 Forschungsgruppen/klinische Forschende aktiv, 7 davon mit Professuren in Doppelanstellung an USZ und UZH. Alle Forschungsgruppen arbeiten mit der Zielsetzung Innovation zum Wohle der Patient:innen zu entwickeln. Im Jahr 2022/2023 wurden jeweils >CHF 3.7 Mio. an Drittmitteln eingeworben und >100 wissenschaftliche Arbeiten publiziert.

Patientenversorgung

53.649 ambulante Patientenbesuche

1.689 stationäre Patientenaustritte

14.014 ambulante Therapien

594 Plasmaaustauschtherapien

86/85 autologe/ allogene Stammzelltransplantationen

29 CAR-T-Zelltherapien

>140 Mio. CHF Ertrag

Forschung

13 Forschungsgruppen

7 Professuren

10 Verbundprojekte mit MOH Beteiligung in Zürich

>110 Publikationen

>3.7 Mio. CHF Drittmittel

>80 offene klinische Studienprotokolle (2022/2023)

Diagnostik

24/7/365 Betrieb

>400.000 häm. Laboranalysen

>24.000 Blutproduktausgaben

>200 Blutstammzellsammlungen

>1.400 BiobankingProben

Zusammenarbeit & Nachwuchsförderung

>390 Mitarbeitende

>70 Ärzt:innen

>70 Wissenschaftler: innen

>50 Medizin-technische Mitarbeiter:innen

18 erzielte Qualifikationen und Titel

>270 Fort- und Weiterbildungen

MOH in Zahlen (Jahr 2023)

Overview 3

The Department of Medical Oncology and Hematology (MOH) offers comprehensive medical care for patients with cancer, benign blood diseases and coagulation disorders.

MOH integrates the areas of Medical Oncology and Hematology at USZ and is an integral part of the Comprehensive Cancer Center Zurich (CCCZ).

Our department has a workforce of >390 staff members: >70 physicians (MOH), >175 nursing staff (USZ Nursing / MTTB), >50 laboratory technicians (USZ MTTB), >75 researchers and clinical trial team members (MOH) as well as <25 documentation specialists and administrative professionals.

In 2022/2023, we recorded 53.448/53.649 patient visits in our outpatient clinics at the USZ campus and airport. In our day clinics, we administered 13.627/14.014 outpatient therapies.

We care for about 50 inpatients daily, including 16 patients on our highly specialized cellular therapies ward. In 2022/2023, we recorded 1.839/1.689 patient discharges.

We cover the entire routine and specialized cellular, molecular hematological and coagulation-physiological diagnostics at USZ in 24-hour operation. Yearly, >400.000 analysis are performed by our hematological diagnostics lab. All diagnoses are discussed and aligned with the Institute of Pathology at the weekly hematopathological conference.

Annually, the MOH immunohematological laboratory and transfusion medicine perform >2.500 immunohematological clarifications and provide >24.000 blood products for the entire USZ.

In 2022/2023, we performed 37/52 unrelated, 30/33 related and 130/128 autologous blood stem cell collections in the MOH apheresis unit. The number of lymphapheresis for CAR T-cell therapies were 34/34 and the total number of inpatient and outpatient plasma exchange therapies 516/594. In 2022/2023, we carried out 95/86 autologous and 67/85 allogeneic blood stem cell transplants and 32/29 CAR T-cell therapies.

The MOH Biobanking and CCCZ Sample Processing Labs handle the standardized processing and storage of tissue and blood samples for research purposes. Annually, >1.400 samples were processed and biobanked by MOH.

As a university department, we continuously strive to improve medical care in all aspects. In 2022/2023, we developed and conducted >80 clinical trials allowing our patients to benefit from novel treatment approaches and the latest research results.

There are 7 university professorships and 13 laboratory research groups/clinical researchers associated with our department. Together, we aim to improve the understanding of cancer biology to develop effective and individualized treatment concepts for our patients. In 2022/2023, we raised >CHF 3.7 million in third-party funding and published >100 scientific publications in peer-reviewed journals p.a.

Medical Care

53.649 outpatient visits

1.689 hospitalizations

14.014 outpatient therapies

594 plasma exchange therapies

86/85 autologous/ allogeneic stem cell transplants

29 CAR-T-Cell therapies

>140 Mio. CHF profit

Research

13 research groups/ clinical researchers

7 professorships

10 research networks with MOH expertise in Zurich

>110 publications

>3.7 Mio. third-party funding

>80 open clinical trials (2022/2023)

Diagnostics

24/7/365 service

>400.000 hematological lab analysis

>24.000 blood products provided

>200 blood stem cell collections

>1.400 biobanked samples

Working together & promoting talents

>390 staff members

>70 physicians

>70 scientists

>50 laboratory technicians 18 completed qualifications/titles

>270 education and training seminars

MOH in Numbers (Year 2023)

Organigramm Klinik für Medizinische Onkologie und Hämatologie (MOH)

Patientenversorgung

Neues Ambulatorium für Krebspatient:innen

Im März 2023 wurde unter Federführung der MOH im USZ Rämigebäude das neue, interdisziplinäre Ambulatorium für Krebspatient:innen eröffnet. Das Ambulatorium umfasst über 2.000 Quadratmeter mit 30 Tages-Therapieplätzen, 17 Untersuchungsund Behandlungsräumen sowie einer Einheit für die Sammlung von Blutstamm- und Immunzellen.

Ausbau der CAR T-Zell Therapie

Die Applikation von CAR T-Zell Therapien wurde in der Klinik weiter ausgebaut. Von 2019 bis 2023 wurde diese neue Therapieform bei 107 Patient:innen mit B-Zell-/ Plasmazell-Neoplasien angewandt.

Patient Engagement

An den CCCZ Patientenakademien informieren wir Betroffene über die neuesten Therapiemöglichkeiten und Forschungsergebnisse bei Krebserkrankungen.

20.10.2022: Multiples Myelom, Organisation – Alexandre Theocharides www.usz.ch/veranstaltung/cancer-academy-myelom

21.9.2023: Stammzelltransplantation, Organisation – Dominik Schneidawind www.usz.ch/veranstaltung/cccz-patientenakademie-stammzelltransplantation

Diagnostik & Labore

Neue Next Generation Sequencing (NGS) Panels

Im MOH Diagnostiklabor wurden neue NGS Panels etabliert. Mit unserem CLL NGS Panel können Mutationen von prognostischer Relevanz (TP53, NOTCH1, SF3B1, BIRC3) nachgewiesen werden, deren Nachweis prädiktiv für das Therapieansprechen ist. Das AML MRD NGS Panel ermöglicht den sensitiven Nachweis (0.1%) von Genen, welche häufig bei Patient:innen mutiert sind und ermöglicht somit eine Beurteilung des Therapieansprechens.

Monitoring von non-Faktor-Therapien der Hämophilie

Im Gerinnungslabor wurden mehrere Methoden etabliert, die das Monitoring fortschrittlicher non-Faktor-Therapien der Hämophilie ermöglichen (z.B. Emicizumab, Messung von Faktor VIII unter Emicizumab, Thrombingenerations-Assay).

Neue Räumlichkeiten für das Stammzelllabor

Im MOH Stammzelllabor werden jährlich über 150 autologe und allogene Blutstammzellsammlungen sowie Lymphozyten für die Lagerung in Stickstoff aufbereitet. In 2022 wurden unsere neuen, hochspezialisierten Räumlichkeiten eingeweiht.

Forschung

Das CCCZ fördert das Leuchtturmprojekt «IMMUNO-CAR ZURICH (ZURICAR)» mit CHF 2 Mio. für die Jahre 2023–2026. PI: Chiara Magnani ZURICAR entwickelt innovative Plattformen für die effektive, flexible, sichere und kosteneffiziente Produktion von Chimeric Antigen Receptor (CAR)-Immunzellen.

The Loop Zurich fördert das Plattformprojekt POLAR (ProteOmics for Lymphoma and Prognostication) mit CHF 1 Mio. für die Jahre 2023–2026. PI: Thorsten Zenz POLAR untersucht die Proteome von Lymphompatient:innen. Die gewonnenen Daten sollen helfen, die Diagnosestellung zu verbessern, neue Behandlungsziele aufzudecken und die Wirksamkeit von Medikamenten vor Verabreichung an Patient:innen zu bewerten.

Das ETH-PHRT Programm fördert die RAPID-Studie (Pharmacoscopy-guided Clinical Standard-of-care in r/r AML) mit CHF 2 Mio. für die Jahre 2024–2025.

PI: Alexandre Theocharides

RAPID ist eine randomisierte, kontrollierte klinische Studie, die sich zum Ziel setzt aufzuzeigen, ob Pharmakoskopie, eine funktionelle Plattform für Präzisionsmedizin (Berend Snijeder, ETH), dazu beiträgt, die klinische Standardtherapieauswahl für Patient:innen mit rezidivierter/refraktärer AML zu verbessern.

Die Helmut Horten Foundation fördert das Projekt iCURE AML (Immunological Approaches to Cure Acute Myeloid Leukemia) mit CHF 4 Mio. für die Jahre 2024–2028. PI: Dominik Schneidawind

Die Etablierung einer Sleeping Beauty Adaptor-FITC CAR T-Zell-Plattform in Kombination mit der Entwicklung neuer small-molecule target-binders wird als Blaupause für eine Pipeline dienen, die innerhalb kurzer Zeit hochpersonalisierte und vielseitige Immuntherapien ermöglichen wird.

Zusammenarbeit, Lernen & Auszeichnungen

2022 MOH Retreat

Am 20.–21.5.2022 fand der 2-jährliche MOH Retreat mit rund 80 Teilnehmenden in der Karthause Ittingen statt, um die Aktivitäten und weitere strategische Ausrichtung der MOH in den Bereichen Patientenversorgung, Forschung und Lehre gemeinsam zu diskutieren.

Die MOH koordiniert und beteiligt sich an interdisziplinären Fachsymposien.

7. CCCZ Immunooncology Symposium, 1.3.2023, Chair: Markus Manz. www.usz.ch/veranstaltung/7th-zurich-immuno-oncology-symposium

3. und 4. CCCZ Precision Oncology Symposium, März 2022 und 2023, Chair: Thorsten Zenz www.usz.ch/veranstaltung/4th-zurich-precision-oncology-symposium

1st Swiss Histiocytosis-Symposium, 20.10.2023, Chair: Wiebke Rösler www.usz.ch/veranstaltung/1st-swiss-histiocytosis-symposium

César Nombela-Arrieta erhält den hoch angesehenen Ellermann-Preis –SGH-SSH am SOHC 2023.

In KAPITEL 12 finden Sie alle Preise und Auszeichnungen unserer Mitarbeitenden in den Jahren 2022 und 2023.

Zusammen lernen

Die Aus- und Weiterbildung des klinischen und akademischen Nachwuchses sowie die persönliche und fachliche Förderung aller unserer Mitarbeitenden ist eine zentrale Aufgabe unserer Klinik.

In der Lehre trägt die MOH zu allen Lehrveranstaltungen Onkologie und Hämatologie des Bachelor- und Master-Curriculums des UZH Studienganges Humanmedizin bei. An der ETH beteiligt sich die MOH an der Lehre des Bachelor-Studiengangs Humanmedizin.

Für die Ausbildung von Studierenden und Unterassistent:innen bietet die MOH zusammen mit den weiteren internistischen Kliniken am USZ ein strukturiertes internistisches Unterassistenz-Curriculum für das Wahlstudienjahr an.

Für die Weiterbildung in der Medizinischen Onkologie ist unsere Klinik vom Schweizerischen Institut für ärztliche Weiter- und Fortbildung (SIWF) als A-Weiterbildungsstätte für Medizinische Onkologie zertifiziert.

Für die Weiterbildung in der Hämatologie ist unsere Klinik vom Schweizerischen Institut für ärztliche Weiter- und Fortbildung (SIWF) als A, sowie D1, D2 und D3 Weiterbildungsstätte zertifiziert.

Die MOH ermöglicht die Weiterbildung von Spezialist:innen für Labordiagnostik in der Hämatologie (FMH und FAMH).

Wir fördern die wissenschaftliche Tätigkeit unserer Ärzt:innen. Neben der regulären Weiter- und Fortbildung ist die Förderung von Physician Scientists ein wichtiges Ziel der MOH.

Hin zur Chancengleichheit unterstützt unsere Klinik die Vereinbarkeit von beruflicher Tätigkeit und familiären/privaten Belangen.

Die MOH koordiniert und beteiligt sich an zahlreichen, regelmässigen internen Fortbildungsangeboten. Dazu gehören unter anderen die MOH Basics Onkologie und Basics Hämatologie, MOH Journal Clubs, Diagnostik-Konferenz zusammen mit der Pathologie und CCCZ Seminar Series. Für unsere ärztlichen und wissenschaftlichen Mitarbeiter:innen organisieren wir regelmässig mehrtägige Retreats, um Interaktionen zwischen den Forschungsgruppen der MOH zu fördern. Unsere wissenschaftlichen Mitarbeiter:innen nehmen zudem wöchentlich an gemeinsamen Labor-Meetings teil, um neue Forschungsdaten auszutauschen. Wir diskutieren zudem wöchentlich neue wissenschaftliche Arbeiten und klinische Studien, um unser Wissen zu erweitern und im klinischen Alltag umzusetzen. In den Jahren 2022 und 2023 hat unsere Klinik das 1. Swiss HistiocytosisSymposium, das 3. und 4. CCCZ Precision Oncology Symposium und das 6. CCCZ Immunooncology Symposium ausgerichtet.

Unsere Klinik bietet ein strukturiertes Programm für Mentoring und Supervison für Assistenzärzt:innen. In 2023 befanden sich 40 Assistenzärzt:innen in der Weiterbildung zur Fachärzt:in für Hämatologie (24) oder Medizinische Onkologie (16).

Von 2009-2023 haben >100 Assistenzärzt:innen in der MOH ihre Weiterbildung bzw. einen Teil ihrer Weiterbildung absolviert, davon >70 in der Hämatologie (seit 2009) und >30 in der Onkologie (seit 2013).

Von den >100 Assistenzärzt:innen, die in der MOH ihre Weiterbildung absolviert haben, haben 49/8 ihre Facharztqualifikation in der Hämatologie/Onkologie abgeschlossen. 29/9 wurden zu Oberärzt:innen, 6/0 zu Oberärzt:innen/meV und 9/2 zu Leitenden Ärzt:innen in der Hämatologie/Onkologie befördert (in der MOH als auch an anderen Spitälern).

Von 2009-2023 arbeiteten >15 Assistenzärzt:innen für 1-2 Jahre in der MOH als Physician Scientist mit 50% «protected research time». 10 Assistenzärzt:innen gingen mit kompetitiven, von der Kreblisga oder vom SNF geförderten, postdoctoral Fellowships für einen Forschungsaufenthalt ins Ausland

«Die MOH hat mir gezeigt, was es bedeutet, ein Physician Scientist zu sein. Man kann sich die Tätigkeit als eine Art von Brücke zwischen zwei doch eher unterschiedlichen Welten vorstellen. Durch die Behandlung von Patient:innen werden Wissenslücken deutlich und damit klinisch relevante Fragestellungen. In der Forschung gehen wir diesen Fragen nach. Durch die Umsetzung der daraus resultierenden wissenschaftlichen Erkenntnisse in die Klinik, versuchen wir letztendlich eine optimale Patientenbetreuung zu fördern.»

Roman Schimmer, Dr. med., Assistenzarzt und Physician Scientist

Qualifikationen

2022

Facharztprüfung/Titel Hämatologie

Tobias Benoit

Albulena Musa

Jan Müller

Philipp Rauch

Matthias Wilk

Facharztprüfung/Titel Onkologie

Marika Valota

Habilitation

Keine

Eingreichte Dissertationen/Titel Dr. med*

Alessa Fischer

Kevin Hofer

Claudia Meloni

Roman Schimmer

Jorune Suipyte

PhD Thesis Defenses/Titel PhD

keine

Master Arbeiten

Katja Dähler

Eva Bär-Gundermann

Robin Krönert

Lena Schmid

Jasmin Alessandra Ulrich

Beförderungen

Lorenz Bankel, OA

Tomas Brezina, OA

Xenia Darphin, OAe i.V.

Jeremy Deuel, OA

Nadja Dietliker, OAe

Ralph Fritsch, LA

Philipp Hockl, OA

Vanessa Mesquita, OAe

César Nombela-Arrieta, Professor ad personam

2023

Facharztprüfung/Titel Hämatologie

Jan Köppel

Maddalena Marconato

Marco Roncador

Sebastian Stolz

Tabea Sutter

Facharztprüfung/Titel Onkologie

Marta Chodup

Franca Lisy

Alex Ring

Habilitation

Steffen Böttcher

Christian Britschgi

Ralph Fritsch

Eingreichte Dissertationen/Titel Dr. med*

Larissa Viviana Isenegger

PhD Thesis Defenses/Titel PhD

Lisa Dietsche

Master Arbeiten

David Brunschwiler

Ivona Dedic

Xenia Schenkel

Elija Simon

Rui Filipe Vieira Dias

Beförderungen

Tobias Benoit, OA

Laura Boos, OAe

Steffen Böttcher, LA

Jana Elegast, OAmeV und Assistenzprofessur

Jan-Dirk Studt, LA

Alexandre Theocharides, LA

Friederike Vetter, OAe

Medizinische Versorgung

Wir sind auf die Diagnostik und Therapie von Tumorerkrankungen aller Organsysteme sowie gutartigen Veränderungen des Blutes und des Blutgerinnungssystems spezialisiert. Dank modernster Analysetechniken in unseren Laboren stellen wir präzise Diagnosen. Unser modernes Behandlungsangebot umfasst zielgerichtete System- und Immuntherapien sowie autologe und allogene Blutstammzelltransplantationen sowie Immunzell-Therapien. Als universitäre Klinik haben wir den Anspruch durch Forschung die Präventions-, Diagnose- und Behandlungsmöglichkeiten kontinuierlich zu verbessern, um unseren Patient:innen in Zukunft noch besser helfen zu können.

«Die Professionalisierung und Erfahrung der Pflegenden spielen eine wichtige und entscheidende Rolle bei der Patientenversorgung. Um gemeinsam mit den Patient:innen eine individuell angepasste und bestmögliche Behandlung und Unterstützung zu ermöglichen, findet ein kontinuierlicher, interdisziplinärer Austausch mit dem ärztlichen Dienst sowie der Psycho-Onkologie, Physiotherapie, Ernährungsberatung und Seelsorge statt.»

Erik Aerts, Abteilungsleiter Pflege

Ambulante und stationäre Patientenversorgung

In unseren spezialisierten Ambulatorien und Tageskliniken am Campus und Flughafen bieten wir eine hochspezialisierte Diagnostik, Beratung und Therapie für Patient:innen mit Tumorerkrankungen aller Organsysteme sowie mit gutartigen Veränderungen des Blutes und des Blutgerinnungssystems. In 2023 wurden in der MOH >53.000 ambulante Besuche verzeichnet.

Wir bieten Erkrankungs-spezifische Spezialsprechstunden für Onkologie, maligne Hämatologie, benigne Hämatologie und Gerinnungsabklärungen. Hier erfolgen auch spezialisierte Interventionen, unter anderem Knochenmark-, Lumbal-, Pleura- oder Aszitespunktionen.

In unseren Tageskliniken werden die Patient:innen von unseren Tagesklinikärzt:innen medizinisch betreut. Die Terminplanung für Patient:innen erfolgt über einen zentralisierten Anmelde- und Dispositionsprozess. In den Jahren 2022/2023 wurden 13.627/14.014 Therapien ambulant verabreicht. Diese umfassen schwerpunktmässig zielgerichtete Systemtherapien, Immun- und zelluläre Therapien, Transfusionen, die Verabreichung von Gerinnungspräparaten und neuen Therapeutika (z.B. RNA-Interferenzmedikamente). Zudem verabreichen wir Infusionstherapien für viele Patient:innen anderer USZ Kliniken, wie zum Beispiel der Dermatologie, Rheumatologie und Inneren Medizin. Wir bieten das gesamte Behandlungsspektrum der medizinischen Onkologie und Hämatologie an.

Erfordert die Therapie einen stationären Aufenthalt, werden unsere Patient:innen auf einer unserer vier Stationen – West J (Interdisziplinäre Privat-Station), West H, OST C 3 und SUED2 E – mit in der Regel >50 belegten Betten von unseren interdisziplinären Teams versorgt. In den Jahren 2022/2023 wurden auf unseren Stationen 1.839/1.689 Patientenaufenthalte betreut.

Die allogene Stammzelltransplantationen sowie CAR T-Zelltherapien werden auf unserer Stamm- und Immunzell-Therapiestation Süd2 E durchgeführt. Zur Infektionsprophylaxe stehen 16 Zimmer mit einer Überdruck-Luftfilteranlage zur Verfügung, die die Raumluft von Krankheitserregern und Umweltkeimen befreit. Pro Jahr werden jeweils >80 autologe und allogene Blutstammzelltransplantationen durchgeführt. Im Jahr 2019 haben wir die CAR T-Zell Therapie in die Klinik eingeführt. Bis Ende 2023 wurde diese neue Therapieform bei 107 Patienten mit B-Zell-/Plasmazell-Neoplasien angewendet.

Das Hämophiliezentrum der MOH betreute regelmässig etwa 50 Patienten mit schwerer, 20 mit mittelschwerer und 60 mit milder Hämophilie A sowie 5 Patienten mit schwerer, 15 mit mittelschwerer und 30 mit milder Hämophilie B. Zusammen mit dem Universitäts-

Kinderspital bildet es das grösste Hämophiliezentrum der Schweiz. Daneben werden 5–10 Konduktorinnen einer Hämophilie A oder B betreut, deren Faktor VIII- oder Faktor IX-Restaktivität auf dem Niveau einer milden Hämophilie vermindert ist (in Auswertung begriffen). Ferner werden Patient:innen mit anderen Faktorenmangelzuständen betreut, beispielweise mit kongenitaler Afibrinogenämie, mit schwerem Faktor XIII-Mangel, mit einem von-Willebrand-Syndrom Typ 3 oder einem schwerer ausgeprägten vonWillebrand-Syndrom Typ 2.

Qualitätssicherung durch Kollaboration und Akkreditierung

Die medizinische Betreuung aller Patient:innen in der MOH geschieht in enger Zusammenarbeit mit der Klinik für Radioonkologie, dem Institut für Diagnostische und Interventionelle Radiologie, der Klinik für Nuklearmedizin, dem Institut für Pathologie und Molekularpathologie, sowie multiplen chirurgischen und internistischen Fachdisziplinen. Der interdisziplinäre Wissensaustausch schafft Synergien in der Patientenversorgung und ermöglicht fachübergreifende Kooperationen.

Die MOH ist integraler Bestandteil des CCCZ. Unsere Klinik ist an allen 17 CCCZ Organzentren durch ihre medizinische Expertise und Zuständigkeit beteiligt und leitet das Zentrum für Hämatologische Neoplasien (HAEZ), das Darmtumorzentrum, das endokrine und neuroendokrine Tumorzentrum und das Sarkomzentrum. Zudem sind wir an der Organisation von 17 Tumorboards des CCCZ beteiligt. Der MOH Klinikdirektor Prof. Markus G. Manz ist seit 2020 Chair des CCCZ Leitungsgremiums. Prof. Andreas Wicki (Stv. Klinikdirektor MOH Medizinische Onkologie) ist Leiter des klinischen Programms und PD Dr. Alexandre Theocharides (Leitender Arzt, MOH) Leiter des klinischen Studienprogramms des CCCZ.

Die MOH steht in engem Austausch und kooperiert mit allen Spitälern der Region in Form der komplexen hämato-onkologischen Diagnostik, der gemeinsamen Patientenbetreuung (Zuweiserspital z.B. im Bereich der molekularen Präzisionsonkologie und zellulären Therapie) und von Beteiligung der Zuweiser an CCCZ Tumorboards. Zudem besteht mit dem Stadtspital Triemli ein strukturierter Austausch im Rahmen der Akkreditierung entsprechend JACIE (The Joint Accreditation Committee ISCT-Europe & EBMT).

Zertifikate und Akkreditierungen: Unsere Klinik ist der kontinuierlichen Qualitätskontrolle und -verbesserung verpflichtet. Dazu unterziehen wir uns reglemässig nationalen und internationalen Zertifizierungen und sind in multiplen Bereichen akkreditiert.

«Am molekularen Tumorboard fügen wir das komplexe Bild des Tumors zusammen, um die von modernsten Technologien erzeugten Daten zum besten Nutzen unserer Patient:innen einzusetzen.»

Andreas Wicki, Prof. Dr. med., Leitender Arzt und Stellvertretender Klinikdirektor Onkologie

MOH Präzisionsonkologie

Die MOH bietet ein modulares Präzisionsonkologie-Programm für bösartige solide Tumoren an. Die Basis des Programms besteht aus einer spezialisierten molekularen Diagnostik (Bulk DNA NGS und Imaging Mass Cytometry) sowie einer strukturierten Erfassung der klinischen Parameter (Swiss Personalized Oncology Minimal Data Set) und einem anonymisierten Abgleich dieser Daten mit internationalen Datenbanken und Richtlinien. Eine enge Zusammenarbeit besteht mit dem Swiss Personalized Health Network SPO-NDS und dem Tumor Profiler Center, welches für die Tumorentitäten Melanom, kolorektales Karzinom, Lunge, Brust und Ovar experimentelle diagnostische Plattformen sowie eine AI-gestützte Modellierung von Therapieansprechen und Nebenwirkungen bietet. Gemeinsam mit dem Institut für Pathologie und Molekularpathologie führen wir ein wöchentliches Molekulares Tumorboard durch, in welchem die Daten aus dem Präzisionsonkologie-Programm zusammengeführt und von einem Expertengremium für jede einzelne Patient:in besprochen werden und zu einem individuellen Therapievorschlag führen. Es werden pro Jahr rund 1.000 Patientenfälle am Molekularen Tumorboard besprochen.

Ein Schwerpunkt der MOH ist das Präzisionsonkologieprogramm für hämatoonkologische Neoplasien. In diesem Bereich verbinden wir neue Behandlungsmethoden innerhalb und ausserhalb klinischer Studien mit molekularer Diagnostik und innovativen Laborplattformen, wie dem Tumor Profiler Center, dem KFSP «Präzisionshämatologie/Onkologie» und den The LOOP Zurich Projekten «INTerCePT» und «POLAR». Ziel ist es, die Behandlung von hämatologischen Neoplasien zu verbessern und die Einzigartigkeit jeder Patientin und jedes Patienten abzubilden und in die Therapieentscheide einzubinden. Durch eine enge Vernetzung mit internationalen Zentren und Studiengruppen bilden unsere Arbeiten dabei auch die Basis für die Etablierung neuer Behandlungsansätze und Leitlinien.

«Im Rahmen von INTeRCePT wurden inzwischen von 243 Patient:innen 626 Proben untersucht und über 280/453 Analysen (scRNAseq/High Dimensional Flow) durchgeführt. Dadurch entsteht ein einmaliger Datensatz, der Medikamentensensitivität vorhersagen lässt.»

Thorsten Zenz, Prof. Dr. med., Leitender Arzt, Lymphome

MOH

Patientversorgung in Zahlen (2022/2023)

1.839/1.689

Stationäre Austritte

53.448/ 53.649 Ambulante Besuche

10.6/11.1

Ø Verweildauer (Tage) 95/86 67/85 autologe/allogene Stammzelltransplantationen 32/29 CAR-T-Zelltherapien

143.557/ 141.613

Gesamtertrag (in TCHF)

Diagnostik/Labore

Die MOH koordiniert die hämatologische Diagnostik am USZ und bietet ein umfangreiches Analysenspektrum im Routine- und Notfall-Labor für interne und externe Partner an. Wir erbringen alle immunhämatologischen Untersuchungen und stellen innerhalb des gesamten Spitals die Blutprodukteversorgung über den Blutspendedienst Zürich sicher. Die Apherese-Einheit führt autologe und allogene Blutstammzellsammlungen durch, gewinnt Lymphozyten für die zelluläre Therapie und bietet für das ganze Spital die Plasmaaustauschtherapie an.

>400.000

Diagnostische Analysen

>24.000

Blutproduktausgaben für das gesamte USZ davon

>14.000 Erythrozytenkonzentrate

>5.100 Thrombozytenkonzentrate

>5.300 Plasmakonservene

>550 Plasmaaustauschtherapien

>200 Blutstammzellsammlungen

Täglich werden im Diagnostiklabor der MOH bis zu 1.400 Proben verarbeitet (jährlich >400.000). Diese umfassen die Blutbildanalytik einschliesslich mikroskopischer Differenzierung (inklusive digitaler Mikroskopie), allgemeine und spezielle Gerinnungsanalyse, die Untersuchung auf Malaria-Erreger, die Untersuchung von Knochenmarkaspiraten und -punktaten. Neben der Routinediagnostik bieten wir ein breites Spektrum an Spezialanalysen an. Dies beinhaltet die spezielle Gerinnungsdiagnostik, die Molekulargenetik (inkl. NGS) und die Immunphänotypisierung.

Das immunhämatologische Labor führt für das gesamte USZ zu jeder Zeit immunhämatologische Abklärungen durch und stellt Blutprodukte bereit, die auch von der Blutspende SRK Zürich bezogen werden. Jährlich werden am USZ >14.000 Erythrozytenkonzentrate (davon ca. 2.200 in der MOH), 5.100 Thrombozytenkonzentrate (davon ca. 2.300 in der MOH) und 5.300 Plasmakonserven (davon ca. 750 in der MOH) transfundiert. Zudem führen wir für das gesamten USZ >2.500 Antikörperabklärungen (u.a. bei antierythrozytären Antikörpern und Autoimmunhämolysen) durch.

In der Apherese-Einheit der MOH wurden in den Jahren 2022/2023 37/52 unverwandte, 30/33 verwandte und 130/128 autologe Blutstammzellsammlungen durchgeführt. Die Anzahl der Lymphapheresen zur CAR T-Zelltherapie betrug 34/34 und die Gesamtzahl der stationären und ambulanten Plasmaaustauschtherapien 516/594.

Unser Stammzellabor ist von JACIE akkreditiert und erfüllt die vorgegebenen höchsten Standards. Jährlich werden über 200 autologe und allogene Blutstammzellsammlungen sowie Lymphozyten für die Lagerung in Stickstoff aufbereitet. Das Team bereitet zudem für die Verabreichung von zellulären Produkten, unter anderem für Stammzelltherapien und CAR T-Zell-Behandlungen, die eingefrorenen Zellen vor. Jährlich werden >450 Beutel mit kryokonservierten Zellen für unsere Patient:innen zur Transfusion auf die MOH Station für Blutstammzellen und zellulären Immuntherapien geliefert.

Für die Aufbereitung von Tumorproben wird in der MOH ein Biobanklabor betrieben. Standardisierte Abläufe ermöglichen es wissenschaftliche Projekte und Studien der Abteilung und von Kooperationspartnern zu unterstützen. Jährlich werden rund 1.400 verschiedene Proben bearbeitet, aufbereitet und eingelagert.

Im Rahmen einer CCCZ-weiten Initiative koordinieren wir zudem ein zentrales Probenverarbeitungslabor – das C3Z Sample Processing Lab (C3Z SPL). Das C3Z SPL wird gemeinsam durch die MOH und das Institut für Pathologie und Molekularpathologie betrieben. Ziel ist die Routineprozessierung nach etablierten SOPs, um eine standardisierte, qualitätsgesicherte Probenverarbeitung für wissenschaftliche Projekte des CCCZ und dessen Kooperationspartner zu garantieren. Im Jahr 2023 wurden >1.400 Proben prozessiert.

«Unser hämatologisches Diagnostiklabor bietet ein sehr breites Spektrum an Analysen zur Beurteilung von Erkrankungen des blutbildenden Systems an. Insbesondere sticht das Labor durch eine Verknüpfung von modernster Diagnostik und medizinischer Expertise heraus. Dies ermöglicht eine genaue Beurteilung der Resultate im klinischen Kontext und legt damit die Grundlage zur personalisierten Therapie der Patienten und Patientinnen. Eine interdisziplinäre Beurteilung in unserer hämatologischen Diagnostikkonferenz ermöglicht eine genaue Diagnosestellung, auch in sehr komplexen Fällen.»

Stefan Balabanov, Prof. Dr. med., Leitender Arzt, Leiter MOH Diagnostiklabor

Klinische Forschung/Studien

Durch klinische Studien können unsere Patient:innen vom neuesten Stand der Wissenschaft und von neu verfügbaren Therapieansätzen profitieren.

In der MOH Studienzentrale arbeiten >10 Studienkoordinatorinnen. Sie kümmern sich um den gesamten Ablauf von Öffnung, Durchführung und Dokumentation von klinischen Studien der Phase I-IV. Wir haben in den Jahren 2022 und 2023 >100 Patient:innen in >80 klinische Studienprotokolle rekrutiert.

Wir sind eines von der Schweizerischen Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) zertifiziertes Phase-I-Zentrum und können somit das ganze Spektrum an frühen Studien anbieten, von Dosisfindungsstudien bis zu Studien mit Medikamenten, welche zum ersten Mal am Menschen eingesetzt werden (first-in-human clinical trials).

Wir arbeiten eng mit (inter)nationalen Netzwerken zusammen. Dazu gehören die SAKK, die European Organisation for Research and Treament of Cancer (EORTC) und die European Thoracic Oncology Platform (ETOP).

«Wir bieten unseren Patient:innen ein breites Angebot an klinischen Studien der Phasen I–IV und schaffen so innovative Therapiemöglichkeiten für alle Entitäten in den verschiedenen Krankheitsstadien mit höchstem medizinischem Fortschritt.»

Anja Lorch, Prof. Dr. med., Leitende Ärztin und Stellvertretende Klinikdirektorin Onkologie, Leiterin MOH Studienzentrale

Offene, diagnostische und interventionelle klinische Studienprotokolle (2022 und 2023)

Phase Anzahl der Studien Eingeschlossene Patient:innen

J CLIN INVEST. 2022 JUN 15;132(12):E158190

Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response

Marconato M, Abela IA, Hauser A, Schwarzmüller M, Katzensteiner R, Braun DL, Epp S, Audigé A, Weber J, Rusert P, Schindler E, Pasin C, West E, Böni J, Kufner V, Huber M, Zaheri M, Schmutz S, Frey BM, Kouyos RD, Günthard HF, Manz MG, Trkola A.

Abstract

Background: Neutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The manner in which human infections respond to therapeutic SARS-CoV-2 antibodies, including convalescent plasma therapy, remains to be fully elucidated.

Methods: We conducted a proof-of-principle study of convalescent plasma therapy based on a phase I trial in 30 hospitalized COVID-19 patients with a median interval between onset of symptoms and first transfusion of 9 days (IQR, 7–11.8 days). Comprehensive longitudinal monitoring of the virological, serological, and disease status of recipients allowed deciphering of parameters on which plasma therapy efficacy depends.

Results: In this trial, convalescent plasma therapy was safe as evidenced by the absence of transfusionrelated adverse events and low mortality (3.3%). Treatment with highly neutralizing plasma was significantly associated with faster virus clearance, as demonstrated by Kaplan-Meier analysis (P = 0.034) and confirmed in a parametric survival model including viral load and comorbidity (adjusted hazard ratio, 3.0; 95% CI, 1.1–8.1; P = 0.026). The onset of endogenous neutralization affected viral clearance, but even after adjustment for their pretransfusion endogenous neutralization status, recipients benefitted from plasma therapy with high neutralizing antibodies (hazard ratio, 3.5; 95% CI, 1.1–11; P = 0.034).

Conclusion: Our data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia before and after onset of the endogenous neutralizing response, and point beyond antibody-based interventions to critical laboratory parameters for improved evaluation of current and future SARS-CoV-2 therapies.

Trial Registration: ClinicalTrials.gov NCT04869072.

Funding: This study was funded via an Innovation Pool project by the University Hospital Zurich; the Swiss Red Cross Glückskette Corona Funding; Pandemiefonds of the UZH Foundation; and the Clinical Research Priority Program “Comprehensive Genomic Pathogen Detection” of the University of Zurich

«This trial was rapidly started under the devastating COVID19 pandemic as a truly interdisciplinary team effort: building on more than 100 years old knowledge from Behring and co-workers, we infused antibodies of COVID-19 recovered patients in infected high-risk patients early in their disease, a procedure, which helped in SARS-CoV-2 clearance. While possibly life-saving for some patients, this study was also a proof of principle, how academia is able to positively and rapidly respond in a common effort to severe new health challenges.»

Markus G. Manz, Prof. Dr. med., Klinikdirektor

NAT CANCER. 2023 MAY;4(5):734-753

Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma

Kropivsek K, Kachel P, Goetze S, Wegmann R, Festl Y, Severin Y, Hale BD, Mena J, van Drogen A, Dietliker N, Tchinda J, Wollscheid B, Manz MG, Snijder B.

Abstract

Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite a growing arsenal of approved therapies, MM remains incurable and in need of guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug and immunotherapy sensitivities across 101 bone marrow samples from 70 patients with MM using multiplexed immunofluorescence, automated microscopy and deep-learning-based single-cell phenotyping. Combined with sample-matched genetics, proteotyping and cytokine profiling, we map the molecular regulatory network of drug sensitivity, implicating the DNA repair pathway and EYA3 expression in proteasome inhibitor sensitivity and major histocompatibility complex class II expression in the response to elotuzumab. Globally, ex vivo drug sensitivity associated with bone marrow microenvironmental signatures reflecting treatment stage, clonality and inflammation. Furthermore, ex vivo drug sensitivity significantly stratified clinical treatment responses, including to immunotherapy. Taken together, our study provides molecular and actionable insights into diverse treatment strategies for patients with MM.

«This study nicely reflects the new area of precision medicine: deep analysis of cancer cells and their environment, including the response of cancer cells to drug exposure, which together will inform on new, more precise and efficient therapies, meaning less side effects and better tumor control.»

Markus G. Manz, Prof. Dr. med., Klinikdirektor

Research Networks

Our department cooperates with numerous partners in Zurich, in Switzerland and abroad. Our collaborative networks combine innovative clinical oncology and hematology, research, technologies and medical bioinformatics to develop novel diagnostic and therapeutic concepts.

Ongoing Projects

Hochschulmedizin Flagship Project: Immuno-TargET

Lead-PIs: Felix Beuschlein (Endocrinology, Diabetology and Clinical Nutrition, USZ), Markus Manz (MOH)

Keywords: Immmunotherapy, Autoimmunity, Neuroendocrine Tumors

Aims: ImmunoTargET aims to transform pathologic mechanisms of autoimmunity into efficient tools to fight cancer of endocrine organs.

Selected Publication: Metastatic Pheochromocytoma and Paraganglioma: Somatostatin Receptor 2 Expression, Genetics, and Therapeutic Responses. Fischer et al. J Clin Endocrinol Metab. 2023

Clinical Research Priority Program (CRPP): ImmunoCure – Targeted Cancer Immunotherapy

Lead-PIs: Patrick Roth (Neurology, USZ), Markus Manz (MOH)

Keywords: Engineered Immuno-therapy, T-cell Engagers and Activators, Car-T Cells and NK-Cells

Aims: ImmunoCure focusses on novel, “engineered” immune-therapeutic concepts such as T cell engaging and activating bispecific antibodies (TEA) as well as CAR-T cell and CAR-NK cell therapy.

Selected Publication: Anti-CD117 CAR T cells incorporating a safety switch eradicate human acute myeloid leukemia and hematopoietic stem cells. Magnani et al. Mol Ther Oncolytics. 2023

The LOOP Zurich: INTeRCePT – Intercept clonal evolution to overcome treatment resistance in childhood and adult blood cancer

Lead-PIs: Thorsten Zenz (MOH), Burkhard Becher (UZH), Nico Beerenwinkel (ETHZ), Jean-Pierre Bourquin (University Children’s Hospital Zurich /UZH), Wolfgang Huber (EMBL), Andreas Moor (ETHZ), Berend Snijder (ETHZ)

Keywords: Blood Cancer, Treatment Resistance, Molecular Profiling

Aims: Precision medicine for blood cancer patients: We investigate the biomolecular reactions in ultra-high resolution at the level of individual cells. This will help us understand the heterogeneity of tumor and normal immune cells, and their interactions.

Selected Publication: Subgroup-specific gene expression profiles and mixed epistasis in chronic lymphocytic leukemia. Lütge et al. Haematologica. 2023

Ongoing Projects

Clinical Research Priority Program (CRPP): Precision Hematology/Oncology

Lead-PIs: Jean-Pierre Bourquin (University Children’s Hospital Zurich), Thorsten Zenz (MOH)

Keywords: Precision Mecicine, Drug Response Screening

Aims: The CRPP “Precision Hematology/Oncology” joins forces to develop a clinical platform for next-generation precision medicine. We aim to apply drug response profiling to personalize treatment of patients and investigate unexpected vulnerabilities at depth.

Selected Publication: Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective noninterventional SMARTrial. Liebers et al. Nat Cancer. 2023

Tumor Profiler Center

Lead-PIs: Andreas Wicki (MOH), Bernd Bodenmiller (UZH/ETH), Viola Heinzelmann (University Hospital Basel)

Keywords: Oncology, Precision Medicine, Therapy Prediction, Functional and Multi-Omics Testing

Aims: The Tumor Profiler Center (TPC) is a cancer-specific research consortium and competence hub of the universities (UZH, ETH) and university hospitals in Zurich.

Selected Publication: Detection of isoforms and genomic alterations by high-throughput full-length single-cell RNA sequencing in ovarian cancer. Dondi et al. Nat Commun. 2023

Amyloidosis and Histiocytosis Registries

PIs: Amyloidosis: Rahel Schwotzer (MOH), Histiocytosis: Wiebke Rösler (MOH)

Keywords: Rare Disease, Collaborative Networks, Interdiscipliary Boards

Aims: The Amyloidosis and LCH registries aim to improve the understanding of the spectrum of these rare diseases, the patient journies and the barriers health care providers and patients face within the Swiss healthcare system.

Selected Publications: Eyes on amyloidosis: microvascular retinal dysfunction in cardiac amyloidosis. Zampiccoli et al. ESC Heart Fail. 2022 / ErdheimChester disease: hairy kidney and coated aorta. Ritter et al. Kidney Int. 2023

CCCZ Lighthouse Project – IMMUNO-CAR ZURICH (ZURICAR)

Principal Investigators: Chiara F. Magnani (MOH), Tobias Weiss (Department of Neurology, USZ), Markus G. Manz (MOH), Bernd Bodenmiller (Department of Quantitative Biomedicine, USZ / Institute for Molecular Health Sciences, ETH)

Funding: CHF 2 Mio. (2023–2026), CCCZ

Keywords: Cancer Immunotherapy, Chimeric Antigen Receptor, Non-viral Gene Transfer

Project Overview

CAR T cell immunotherapy is a new perspective of precision medicine which use gene transfer technology to generate T cells with improved anti-tumor activity. Despite their success in B-cell neoplasm, efficacy of CAR T-cell therapy is still limited in myeloid and solid tumors due to immunosuppressive tumor microenvironments, heterogeneous diseases, and poor tumor infiltration. Furthermore, most CAR T-cell therapies depend on viral vectors, which are associated with logistical complexity and high costs. The goal of the project is to establish and apply two complementary, innovative next-generation clinical CAR immune cell platforms which rely on virus-free technology. This will be accompanied by research on CAR immunomonitoring and efficacy improvement.

Preliminary Work/Selected Publications

Sleeping Beauty-engineered CAR T cells achieve anti-leukemic activity without severe toxicities. Magnani CF, Gaipa G, Lussana F, Belotti D, Gritti G, Napolitano S, Matera G, Cabiati B, Buracchi C, Borleri G, Fazio G, Zaninelli S, eTettamanti S, Cesana S, Colombo V, Quaroni M, Cazzaniga G, Rovelli A, Biagi E, Galimberti S, Calabria A, Benedicenti F, Montini E, Ferrari S, Introna M, Balduzzi A, Valsecchi MG, Dastoli G, Rambaldi A, Biondi A. J Clin Invest. 2020 Nov 2;130(11):6021-6033.

Anti-human CD117 CAR T-cells Efficiently Eliminate Healthy and Malignant CD117-expressing Hematopoietic Cells. Myburgh R, Kiefer JD, Russkamp NF, Magnani CF, Nuñez N, Simonis A, Pfister S, Wilk CM, McHugh D, Friemel J, Müller AM, Becher B, Münz C, van den Broek M, Neri D, Manz MG. Leukemia. 2020 Oct;34(10):2688-2703.

Multifunctional mRNA-based CAR T cells display promising anti-tumor activity against glioblastoma.

Meister H, Look T, Roth P, Pascolo S, Sahin U, Lee S, Hale BD, Snijder B, Regli L, Ravi VM, Heiland DH, Sentman CL, Weller M, Weiss T. Clin Cancer Res. 2022 Nov 1;28(21):4747-4756.

Overview of the ZURICAR project aimed at establishing platforms of Chimeric Antigen Receptor (CAR) immunotherapy to treat oncologic patients with unmet medical needs.

New Projects

Pharmacoscopy-guided Clinical Standard-of-care in r/r AML (RAPID)

Investigators: Alexandre Theocharides (MOH), Markus G. Manz (MOH), Berend Snijder (ETH)

Funding: CHF 2 Mio. (2024–2026), ETH PHRT

Keywords: Acute Myeloid Leukemia, Pharmacoscopy, Precision medicine

Project Overview

With an overall survival of below 12 months, the outcome of relapsed/refractory acute myeloid leukemia (rr-AML) is poor, making it a critical challenge to identify effective therapies at this stage. The RAPID trial aims to show that Pharmacoscopy (PCY), an ETH-developed functional precision medicine platform, helps improve therapy selection for patients suffering from rr-AML, for the first time in a randomized and controlled clinical trial. In doing so, we aim to validate PCY for precision oncology in AML, improve the lives of rr-AML patients, and further develop the patent-pending PCY 2.0 platform, optimized for distributed drug testing in clinical centers in Switzerland.

Preliminary Work/Selected Publications

The Tumor Profiler Study: integrated, multi-omic, functional tumor profiling for clinical decision support. A, Bonilla X, Chevrier S, Lehmann KV, Singer F, Toussaint NC, Esposito C, Mena J, Milani ES, Casanova R, Stekhoven DJ, Wegmann R, Jacob F, Sobottka B, Goetze S, Kuipers J, Sarabia Del Castillo J, Prummer M, Tuncel MA, Menzel U, Jacobs A, Engler S, Sivapatham S, Frei AL, Gut G, Ficek J, Miglino N; Tumor Profiler Consortium, Aebersold R, Bacac M, Beerenwinkel N, Beisel C, Bodenmiller B, Dummer R, Heinzelmann-Schwarz V, Koelzer VH, Manz MG, Moch H, Pelkmans L, Snijder B, Theocharides A, Tolnay M, Wicki A, Wollscheid B, Rätsch G, Levesque MP. Cancer Cell. 2021 Jan 20;S1535-6108(21)00048-9.

Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematological Cancers and Identifies Exceptional Responders.

Kornauth C, Pemovska T, Vladimer GI, Bayer G, Bergmann M, Eder S, Eichner R, Erl M, Esterbauer H, Exner R, Felsleitner-Hauer V, Forte M, Gaiger A, Geissler K, Greinix HT, Gstöttner W, Hacker M, Hartmann BL, Hauswirth AW, Heinemann T, Heintel D, Hoda MA, Hopfinger G, Jaeger U, Kazianka L, Kenner L, Kiesewetter B, Krall N, Krajnik G, Kubicek S, Le T, Lubowitzki S, Mayerhoefer ME, Menschel E, Merkel O, Miura K, Müllauer L, Neumeister P, Noesslinger T, Ocko K, Öhler L, Panny M, Pichler A, Porpaczy E, Prager GW, Raderer M, Ristl R, Ruckser R, Salamon J, Schiefer AI, Schmolke AS, Schwarzinger I, Selzer E, Sillaber C, Skrabs C, Sperr WR, Srndic I, Thalhammer R, Valent P, van der Kouwe E, Vanura K, Vogt S, Waldstein C, Wolf D, Zielinski CC, Zojer N, Simonitsch-Klupp I, Superti-Furga G, Snijder B, Staber PB. Cancer Discov. 2022 Oct 11;12, 372–387.

Study design and management of the RAPID trial in patients with relapsed/refractory acute myeloid leukemia (rr-AML). ICF, informed consent form. RR-AML, relapsed/refractory acute myeloid leukemia. PCY, pharmacoscopy. CR, complete remission. Allo-HSCT, allogeneic hematopoietic stem cell transplantation. TRM, treatment-related mortality.

Immunological Approaches to Cure Acute Myeloid Leukemia (iCure-AML)

Principal Investigators: Dominik Schneidawind (MOH), Chiara F. Magnani (MOH), Markus G. Manz (MOH), Burkhard Becher (UZH), Berend Snijder (ETH), Dario Neri (ETH)

Funding: CHF 4 Mio. (2024–2028), Helmut Horten Foundation

Keywords: Acute Myeloid Leukemia, Adaptor CAR T Cells, Sleeping Beauty Transposon, Small Molecule Adaptors

Project Overview

Acute myeloid leukemia (AML) and high-risk myelodysplastic neoplasia (hrMDS) are aggressive hematologic malignancies with a particular poor prognosis. We hypothesize that our Sleeping Beauty Adaptor-FITC (SB Ad-FITC) CAR T-cell platform coupled with anti-CD117 binders can facilitate the academic translation of innovative approaches to eradicate AML/ hrMDS cells and, concomitantly, serve as a non-cytotoxic conditioning before allogeneic hematopoietic stem cell transplantation. This will in best case fundamentally change current clinical practice and improve outcomes, first in patients with AML/hrMDS relapse after allogeneic hematopoietic stem cell transplantation, and subsequently in patients at earlier treatment stages with acceptable toxicity. Finally, we envision establishing a pipeline for the discovery of further highly effective target binders that can be coupled with our sleeping beauty adaptor CAR T-cells.

Preliminary Work/Selected Publications

Anti-CD117 CAR T cells incorporating a safety switch eradicate human acute myeloid leukemia and hematopoietic stem cells.

Magnani CF, Myburgh R, Brunn S, Chambovey M, Ponzo M, Volta L, Manfredi F, Pellegrino C, Pascolo S, Miskey C, Ivics Z, Shizuru JA, Neri D, Manz MG. Mol Ther Oncolytics. 2023 Sep 21;19;30:56-71 .

Impact of Ligand Size and Conjugation Chemistry on the Performance of Universal Chimeric Antigen Receptor T-Cells for Tumor Killing.

Pellegrino C, Favalli N, Sandholzer M, Volta L, Bassi G, Millul J, Cazzamalli S, Matasci M, Villa A, Myburgh R, Manz MG, Neri D. Bioconjug Chem. 2020 Jun 9;31, 1775-1783.

Anti-human CD117 CAR T-cells efficiently eliminate healthy and malignant CD117-expressing hematopoietic cells. Myburgh R, Kiefer JD, Russkamp NF, Magnani CF, Nuñez N, Simonis A, Pfister S, Wilk CM, McHugh D, Friemel J, Müller A, Becher B, Münz C, van den Broek M, Neri D, Manz MG. Leukemia. 2020 Oct;34, 2688-2703.

Sleeping Beauty-engineered CAR T cells achieve antileukemic activity without severe toxicities.

Magnani CF, Gaipa G, Lussana F, Belotti D, Gritti G, Napolitano S, Matera G, Cabiati B, Buracchi C, Borleri G, Fazio G, Zaninelli S, Tettamanti S, Cesana S, Colombo V, Quaroni M, Cazzaniga G, Rovelli A, Biagi E, Galimberti S, Calabria A, Benedicenti F, Montini E, Ferrari S, Introna M, Balduzzi A, Valsecchi MG, Dastoli G, Rambaldi A, Biondi A. J Clin Invest. 2020 Nov 2;130(11):6021-6033.

Pipeline for the discovery of highly effective target binders that can be coupled with our sleeping beauty adaptor CAR T-cells.

ProteOmics for Lymphoma and Prognostication (POLAR)

Principal Investigators: Thorsten Zenz (MOH), Valentina Boeva (Computational Cancer Genomics, ETH), Marco Bühler (Pathology, USZ), Christoph Messner (Precision Proteomics Center Davos, UZH)

Funding: CHF 1 Mio. (2024–2026), The LOOP Zurich

Keywords: Lymphoma, Proteome, Precision Oncology

Project Overview

Many lymphoma patients cannot be cured with current treatment strategies, and accurate diagnosis remains challenging even for experts. The goal of POLAR is to develop a platform that can integrate the entire protein profile (proteome) of lymphomas into clinical decision making. The platform will enable physicians and researchers to access and utilize the vast amounts of data generated by proteomic measurements to improve diagnosis, reveal new treatment targets, and help assess the effectiveness of drugs before administration. This enables personalized, precision oncological lymphoma treatment and addresses a long-term medical need in cancer diagnostics: the precise alignment of diagnosis and individual therapies based on molecular profiles. The project also lays the foundation for a nationwide lymphoma registry involving the University Hospital Basel and the Institute for Research in Biomedicine in Bellinzona.

Preliminary Work/Selected Publications

Multi-omics reveals clinically relevant proliferative drive associated with mTOR-MYC-OXPHOS activity in chronic lymphocytic leukemia.

Lu J, Cannizzaro E, Meier-Abt F, Scheinost S, Bruch PM, Giles HA, Lütge A, Hüllein J, Wagner L, Giacopelli B, Nadeu F, Delgado J, Campo E, Mangolini M, Ringshausen I, Böttcher M, Mougiakakos D, Jacobs A, Bodenmiller B, Dietrich S, Oakes CC, Zenz T*, Huber W*. Nat Cancer. 2021 Aug;2(8):853-864. *co-corresponding authors .

Graphical abstract of the research and development plan: The project is organized in working packages with four well-defined objectives. WP1 and WP2 will generate and integrate the data (proteomics, clinicopathological, and -omics data). WP3 will develop the biomedical informatics platform with tools for different uses (clinical and research). In WP4, we will apply the POLAR* pipeline (WP1-3) to new cases to generate a POLAR* Report which will be discussed in the Lymphoma Molecular Board. The project fully complies with FAIR datasharing principles.

Laboratory Research Groups 11

As an academic department, we continuously strive to improve medical care in all aspects. There are 7 university professorships and 13 laboratory research groups/clinical researchers associated with MOH. In 2022/2023, MOH raised >CHF 3.7 million in third-party funding and published overall >100 scientific publications in peer-reviewed journals.

We establish interdisciplinary programs in precision oncology, immunotherapies and stem cell transplantation/ cellular therapies, which combine innovative cancer medicine and cancer research. We aim to improve the understanding of cancer biology and pathology to develop effective and individualized treatment concepts for our patients.

Diagnostics of Hematological Neoplasms

Keywords

Myeloid neoplasms, hematological diagnostics, next generation sequencing, flow cytometry, digital microscopy, machine learning

Aims

The focus of our laboratory is to optimize the diagnostics of myeloid and lymphoid neoplasms. In particular, we aim to establish new assays for sensitive detection of minimal residual disease using digital PCR, next generation sequencing and flow cytometry. Furthermore, we use machine learning to optimize digital microscopy of blood and bone marrow cells and to predict diseases from lab values.

Research Highlight

We established a workflow for validation of NGS assays for diagnosis of acute myeloid leukemia. Our results support the reliability of the Acrometrix Oncology Hotspot Control to validate and compare sequencing panels for hematological diseases and show which panel-software combination (platform) has the best performance.

Heat map of genes with missed [false-negative (FN)] and unexpected [false-positive (FP)] mutations for the Acrometrix Hotspot sample, as reported by three different platforms [AML (Acute Myeloid Leukemia) Cancer Research Panel (AMLP), TruSight Myeloid Sequencing Panel (TSMP), and Myeloid Solution Panel (MYS) Numbers of FNs are coded by color range from white to blue to red, and the numbers of FPs are coded by color ranges from white to green to yellow. The bar plots on the left or the right side of each heat map indicate the sum of length of all amplicons attributed to each respective gene. Wagner et al., J Mol Diagn. 2022

Selected Publications (2022–2023)

Intrapatient competition of VEXAS sydrome and CML clones. Djerbi N, Zimmermann K, Roncador M, Becker MO, Manz MG, Balabanov S.; Blood Adv. 2023 Nov 28;7(22):6815-6818

Proteogenetic drug response profiling elucidates targetable vulnerabilities of myelofibrosis. Wildschut MHE, Mena J, Dördelmann C, van Oostrum M, Hale BD, Settelmeier J, Festl Y, Lysenko V, Schürch PM, Ring A, Severin Y, Bader MS, Pedrioli PGA, Goetze S, van Drogen A, Balabanov S, Skoda RC, Lopes M, Wollscheid B, Theocharides APA, Snijder B. Nat Commun. 2023 Oct 12;14(1):6414

Comprehensive Validation of Diagnostic Next-Generation Sequencing Panels for Acute Myeloid Leukemia Patients. Wagner U , Wong C , Camenisch U , Zimmermann K, Rechsteiner M, Valtcheva N, Theocharides A, Widmer C, Manz MG, Moch H, Wild PJ, Balabanov S. J Mol Diagn. 2022 Aug;24(8):935-954

A multicenter real-world evidence study in the Swiss treatment landscape of chronic myeloid leukemia. Cantoni N, Sommavilla R, Seitz P, Kulenkampff E, Kahn S , Lambert JF, SchmidtA, Zenhaeusern R, Balabanov S. BMC Cancer. 2022 Nov 19;22(1):1192

Standardization of molecular monitoring of CML: results and recommendations from the European treatment and outcome study. White H, Salmon M, Albano F, Søs Auður Andersen C, Balabanov S, ….. , Cross NCP. Leukemia. 2022 Jul;36(7):1834-1842

Stefan Balabanov stefan.balabanov@usz.ch

Funding Our research is supported by grants from PHRT and Innosuisse.

Steffen Böttcher Steffen.Boettcher@usz.ch

Research Group Members (A–Z)

– Jonas Fullin, MSc/PhD candidate – Nancy Klemm, MSc/PhD candidate – Christian Koch, MD (Physician-scientist) – Nils Konrad, cand. med./Master student – Roman Schimmer, MD/Physician-scientist – Ebru Topçu, MSc/PhD candidate

Funding

Our research is supported by the Swiss National Science Foundation, Swiss Cancer League, Fondation Peter Anton & Anna Katharina Miescher, Promedica Foundation, Helmut Horten Foundation, and the ItenKohaut Foundation.

Translational Cancer Research Lab

Keywords

TP53,Pre-Malignancies, Clonal Hematopoiesis, Acute Myeloid Leukemia

Aims

We generate novel in vitro and in vivo models of TP53-mutant hematological (pre-)malignancies with a special focus on acute myeloid leukemia (AML). We use human genetics data, precise CRISPR-based genome editing, classical molecular biology as well as largescale functional genomics to elucidate disease mechanisms and to identify cancer vulnerabilities. Our ultimate goal is to improve outcomes in cancer patients.

Research Highlight

TP53 mutations confer increased resistance to hypomethylating agents as well as BCL-2 inhibition in vitro. (A) Graphical representation of the experimental workflow for generating MOLM13-TP53 isogenic cell lines and MV4-11 and OCI-AML3 TP53KO cell lines. (B) MOLM13-TP53 isogenic AML cell lines were treated with DMSO, decitabine, azacitidine, or venetoclax at increasing concentrations for 72 hours, after which cell viability was assessed using a CellTiter-Glo luminescent assay (symbols represent averages from 3 independent experiments; error bars indicate standard error of the mean). Schimmer et al. Blood Adv. 2022

Selected Publications (2022–2023)

Enhanced TP53 reactivation disrupts MYC transcriptional program and overcomes venetoclax resistance in acute myeloid leukemias. Nishida Y, Ishizawa J, Ayoub E, Montoya RH, Ostermann LB, Muftuoglu M, Ruvolo VR, Patsilevas T, Scruggs DA, Khazaei S, Mak PY, Tao W, Carter BZ, Boettcher S, Ebert BL, Daver NG, Konopleva M, Seki T, Kojima K, Andreeff M. Sci Adv. 2023 Dec;9(48):eadh1436

PPM1D modulates hematopoietic cell fitness and response to DNA damage and is a therapeutic target in myeloid malignancy. Miller PG, Sperling AS, Mayerhofer C, McConkey ME, Ellegast JM, Da Silva C, Cohen DN, Wang C, Sharda A, Yan N, Saha S, Schluter C, Schechter I, Słabicki M, Sandoval B, Kahn J, Boettcher S, Gibson CJ, Scadden DT, Stegmaier K, Bhatt S, Lindsley RC, Ebert BL. Blood. 2023 Dec 14;142(24):2079-2091

Combined inhibition of BCL-2 and MCL-1 overcomes BAX deficiency-mediated resistance of TP53mutant acute myeloid leukemia to individual BH3 mimetics. Carter BZ, Mak PY, Tao W, Ayoub E, Ostermann LB, Huang X, Loghavi S, Boettcher S, Nishida Y, Ruvolo V, Hughes PE, Morrow PK, Haferlach T, Kornblau S, Muftuoglu M, Andreeff M. Blood Cancer J. 2023 Apr 24;13(1):57

TP53 mutations confer resistance to hypomethylating agents and BCL-2 inhibition in myeloid neoplasms. Schimmer RR, Kovtonyuk LV, Klemm N, Fullin J, Stolz SM, Mueller J, Caiado F, Kurppa KJ, Ebert BL, Manz MG, Boettcher S. Blood Adv. 2022 Jun 14;6(11):3201-3206

Degradation of GSPT1 causes TP53-independent cell death in leukemia while sparing normal hematopoietic stem cells. Sellar RS, Sperling AS, Słabicki M, Gasser JA, McConkey ME, Donovan KA, Mageed N, Adams DN, Zou C, Miller PG, Dutta RK, Boettcher S, Lin AE, Sandoval B, Quevedo Barrios VA, Kovalcik V, Koeppel J, Henderson EK, Fink EC, Yang L, Chan A, Pokharel SP, Bergstrom EJ, Burt R, Udeshi ND, Carr SA, Fischer ES, Chen CW, Ebert BL. J Clin Invest. 2022 Aug 15;132(16):e153514

Experimental Oncology (Sarcoma) Lab

Keywords

Soft tissue sarcomas (STS), clear cell sarcoma (CCSA), ex vivo drug profiling, IBDS-SARC

Aims

– We aim to explore novel approaches to therapeutically target clear cell sarcoma, a rare soft tissue sarcoma subtype.

– In collaboration with ETH Zurich (Prof. Berend Snijder), we have established an ex vivo drug screening platform for patients with soft tissue sarcomas (IBDS-SARC) and plan to expand the cohort.

Research Highlight

As part of the SAKK network, we were active in recruiting patients into the SAKK 57/16 NAPAGE clinical trial. In this trial, patients with metastasized or inoperable, pretreated soft tissue sarcomas were treated with a combination of nab-paclitaxel and gemcitabine. It was a phase-1b/2 clinical trial assessing tolerability, as well as efficacy read-outs. We found this combination to be safe and to have promising clinical activity, in particular, in L-sarcomas. This warrants further investigation in larger clinical trials.

Median overall survival of soft tissue sarcoma patients included in the SAKK 57/16 clinical trial, studying the combination of nab-paclitaxel with gemcitabine. Digklia et al. European Journal of Cancer. 2023

Christian Britschgi christian.britschgi@usz.ch

Research Group Members (A–Z) – Lorenz Bankel, MD – Larissa Isenegger, MMed – Laura Leuenberger, MSc/PhD candidate – Elisa Zaninotto, MD

Funding

Our research is supported by Krebsliga Zürich, the Stiftung zur Krebsbekämpfung, the Iten-Kohaut Stiftung/USZ Foundation, The Swiss Personalized Health Network, The Stiftung für angewandte Krebsforschung and an unrestricted research grant from Bayer.

Selected Publications (2022–2023)

Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma. Planas-Paz L, Pliego-Mendieta A, Hagedorn C, Aguilera-Garcia D, Haberecker M, Arnold F, Herzog M, Bankel L, Guggenberger R, Steiner S, Chen Y, Kahraman A, Zoche M, Rubin MA, Moch H, Britschgi C, Pauli C. EMBO Mol Med. 2023 Apr 11;15(4):e16863

MTPpilot: An Interactive Software for Visualization of Next-Generation Sequencing Results in Molecular Tumor Boards. Kahraman A, Arnold FM, Hanimann J, Nowak M, Pauli C, Britschgi C, Moch H, Zoche M. JCO Clin Cancer Inform. 2022 Aug;6:e2200032

Molecular and immunophenotypic characterization of SMARCB1 (INI1) – deficient intrathoracic Neoplasms. Haberecker M, Bühler MM, Mendieta AP, Guggenberger R, Arnold F, Markert E, Rechsteiner M, Zoche M, Britschgi C, Pauli C. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc. 2022 Dec;35(12):1860-1869

Structure-based prediction of BRAF mutation classes using machine-learning approaches. Krebs FS, Britschgi C, Pradervand S, Achermann R, Tsantoulis P, Haefliger S, Wicki A, Michielin O, Zoete V. Sci Rep. 2022 Jul 22;12(1):12528

A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial. Soo RA, Han JY, Dafni U, Cho BC, Yeo CM, Nadal E, Carcereny E, de Castro J, Sala MA, Bernab R, Coate L, Provencio Pulla M, Garcia Campelo R, Cuffe S, Hashemi SMS, Froh M, Massuti B, Garcia-Sanchez J, DM, Majem M, Sanchez-Torres JM, Britschgi C, Pless M, Dimopoulou G, Roschitzki-Voser H, Ruepp B, Rosell R, Stahel RA, Peters S. Annals of Oncology. 2022 Feb;33(2):181-92

Jana Ellegast

jana.ellegast@usz.ch

Research Group Members (A–Z)

– Artemis Baumann, MSc/PhD candidate

– Monika Burócziová, PhD/Senior staff scientist

Funding

Our research is supported by the Rally Foundation, the American Society of Hematology (ASH), and the European Society of Hematology (EHA).

Cancer Inflammation Lab

Keywords

Inflammatory Signaling, Myeloid Malignancies, Acute Myeloid Leukemia (AML), Myeloid Dysplastic Syndrome (MDS), Clonal Hematopoiesis of Indeterminate Potential (CHIP), Sarcoma, Drug Resistance, Patient-Derived Xenograft (PDX) models

Aims

Our primary research objectives are to decode the molecular basis of inflammatory programs in AML and to leverage this understanding for the discovery of immune-modulating targets at the crossroads of inflammation and gene dependencies. We will uncover the interplay of cell-intrinsic and -extrinsic inflammation within the bone marrow and research how environmental factors can enhance anti-leukemic effects. We will unravel inflammatory signaling in the context of drug resistance. Sarcoma is a second research focus of our lab, and we aim to exploit inflammatory signaling for patients‘ benefit equally.

Research Highlight

Our previous studies highlight that AML blasts depend on tight regulation of cell-intrinsic inflammatory signaling. Perturbation of this tightly balanced level of inflammation can be exploited as cell-intrinsic, self-directed immunotherapy. We recently characterized and validated a novel dependency in AML, interferon regulatory factor 2 binding protein 2 (IRF2BP2), that controls inflammation in leukemia cells. We uncovered that its perturbation leads to an overwhelming cell-intrinsic inflammatory response resulting in cell death. This discovery identifies acute hyper-inflammation as a vulnerability of leukemia cells, exemplifies its therapeutic potential, and lays the foundation for future research.

Figure 1: Model of lethal hyperinflammation in AML blast following IRF2BP2 perturbation.

Model of lethal hyperinflammation in AML blast following IRF2BP2 pertubation. Ellegast et al. Cancer Discovery. 2022

Selected Publications (2022–2023)

PPM1D modulates hematopoietic cell fitness and response to DNA damage and is a therapeutic target in myeloid malignancy. Miller PG, Sperling AS, Mayerhofer C, McConkey M, Ellegast JM, Da Silva C, Cohen DN, Wang C, Sharda A, Yan N, Saha S, Schluter C, Schechter IA, Słabicki M, Sandoval B, Kahn J, Boettcher S, Gibson CJ, Scadden DT, Stegmaier K, Bhatt S, Lindsley RC, Ebert BL. Blood. 2023; 142(24):2079-2091

The ETS transcription factor ETV6 constrains the transcriptional activity of EWS-FLI to promote Ewing sarcoma. Lu D, Ellegast JM, Ross KN, Malone CF, Lin S, Mabe NW, Dharia NV, Meyer A, Conway A, Selich-Anderson J, Taslim C, Byrum AK, Seong BKA, Adane B, Gray NS, Rivera MN, Lessnick SL, Stegmaier K. Nature Cell Biol. 2023 Feb;25(2):285-297

Unleashing cell-intrinsic inflammation as a strategy to kill AML blasts. Ellegast JM, Alexe G, Hamze A, Lin S, Uckelmann HJ, Rauch PJ, Pimkin M, Ross LS, Dharia NV, Robichaud AL, Saur Conway A, Khalid D, Perry JA, Wunderlich M, Benajiba L, Pikman Y, Nabet B, Gray NS, Orkin SH, Stegmaier K. Cancer Discov. 2022 Jul 6;12(7):1760-1781

A distinct core regulatory module enforces oncogene expression in KMT2A-rearranged leukemia. Harada T, Heshmati Y, Kalfon J, Perez MW, Xavier Ferrucio J, Ewers J, Hubbell Engler B, Kossenkov A, Ellegast JM, Yi JS, Bowker A, Zhu Q, Eagle K, Liu T, Kai Y, Dempster JM, Kugener G, Wickramasinghe J, Herbert ZT, Li CH, Vrabič Koren J, Weinstock DM, Paralkar VR, Nabet B, Lin CY, Dharia NV, Stegmaier K, Orkin SH, Pimkin M. Genes Dev. 2022 Mar 1;36(5-6):368-389

IRF2BP2

Translational GI Oncology Lab

Keywords

Gastrointestinal Cancer, Precision Treatment, Oncogenic Signalling, Organoid Modelling, Liquid Biopsy

Aims

To advance precision treatment of gastrointestinal and hepato-pancreatico-biliary (HPB) tumors. To improve oncogene targeting strategies and target the development of acquired resistance in pancreatic and colorectal cancers. To personalize systemic GI Cancer treatment through molecular response monitoring.

Research Highlight

We designed, planned and organized PARTACER-Suisse, a prospective multicenter an investigator-initiated prospective HRO chapter 2 multicenter study, enrolling patients undergoing molecularly targeted treatment with CE for BRAF V600E-mutated mCRC. PARTACER-Suisse is organized through Swiss Group for Clinical Cancer Research (SAKK, trial number 41-23). We acquired sufficient funding for the clinical part of the study, and submitted grant popopsals for the complete set of translational work planned. Ethics submission is ongoing, recruitment is planned from Q3/2024.

PARTACER-Suisse: Schematic representation of the PARTACER-Suisse study workflow. The study will prospectively enrol patients with confirmed BRAF V600E-mutated mCRC prior to molecularly targeted treatment with encorafenib and cetuximab. For the clinical part of the study, paired tissue and liquid samples will be analyzed by targeted DNA NGS (Foundation Medicine platform), and a comparative research report will be reported back to the recruiting site. For the translational part, tissue and liquid biopsies will undergo comprehensive molecular analysis including gene expression profiling and multiples analysis or the tumor immune microenvironment. Patient-derived organoids (PDOs) established from pre- and post-treatment biopsies will be exploited for treatment modelling in vitro, aiming to establish novel strategies to prevent, delay, modify or overcome acquired resistance. Abstract SOHC 2023

Selected Publications (2022–2023)

BRAF(Δ β 3- α C) in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability. Lauinger, M., Christen, D., Klar, R. F. U., Roubaty, C., Heilig, C. E., Stumpe, M., Knox, J. J., Radulovich, N., Tamblyn, L., Xie, I. Y., Horak, P., Forschner, A., Bitzer, M., Wittel, U. A., Boerries, M., Ball, C. R., Heining, C., Glimm, H., Fröhlich, M., Hübschmann, D., Gallinger, S., Fritsch, R., Fröhling, S., O’Kane, G. M., Dengjel, J. and Brummer, T. Sci Adv. 2023 Sep;9, eade7486

Retrospective Analysis of Treatment Pathways in Patients With BRAF(V600E)-mutant Metastatic Colorectal Carcinoma - MORSE(CRC). Gerger, A., Eisterer, W., Fuxius, S., Bastian, S., Koeberle, D., Welslau, M., Sanoyan, D.A., Maas, C., Uhlig, J., Fenchel, K., Greil, R., E, V.D.H., Agocs, G.R., Weide, R., Schwager, M., Reichenbach, F., Modest, D.P., and Fritsch, R. Anticancer Res. 2022 Oct; 42, 4773-4785

ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer. Akhoundova, D., Hussung, S., Sivakumar, S., Töpfer, A., Rechsteiner, M., Kahraman, A., Arnold, F., Angst, F., Britschgi, C., Zoche, M., Moch, H., Weber, A., Sokol, E., and Fritsch, R.M. Int J Cancer. 2022 Dec 15; 151, 2161-2171

Two phase I studies of BI 836880, a vascular endothelial growth factor/angiopoietin-2 inhibitor, administered once every 3 weeks or once weekly in patients with advanced solid tumors. Le Tourneau, C., Becker, H., Claus, R., Elez, E., Ricci, F., Fritsch, R., Silber, Y., Hennequin, A., Tabernero, J., Jayadeva, G., Luedtke, D., He, M., and Isambert, N. ESMO Open. 2022 Oct; 7, 100576

Ralph Fritsch ralph.fritsch@usz.ch

Research Group Members (A–Z) – Meret Geissmann, cand. med. – Saskia Hussung, Dr. med. – Bianca de Nard, cand. med. – Clelia Pistoni, MSc – Mia Roth, BSc

Funding

Our research is supported by Iten-Kohaut Foundation, Innovationspool USZ, Stiftung für klinische Forschung, Novartis Foundation, Science Foundation for Oncology, Pierre Fabre Pharma AG.

Chiara Magnani

chiara.magnani@usz.ch

Research Group Members (A–Z)

– Sarah Alberio, PhD student

– Silvan Brunn, PhD student

– Morgane Chambovey, PhD student

– Francesco Manfredi, Postdoc

– Marianna Ponzo, Postdoc

Funding

Our research is supported by the Swiss National Science Foundation, the San Salvatore Foundation, Cancer Research UK, AIRC, C3Z LIGHTHOUSE PROJECT, Helmuth Horten Stiftung.

Cancer Immunotherapy and Cell Engineering Lab

Keywords

Cancer Immunotherapy, Gene Therapy, Hematological Malignancies, Chimeric Antigen Receptor T cells, Cellular Therapy

Aims

Our research focuses on immunotherapy and uses genetic engineering to unleash our immune system against cancer. Specifically, we aim to apply non-viral engineering to generate next-generation CAR T cells.

Research Highlight

Discrimination between hematopoietic stem cells and leukemic stem cells remains a major challenge for AML immunotherapy. In this study, we exploit non-viral technology to achieve early termination of CAR T-cell activity to prevent incoming graft rejection. For this purpose, we used a Sleeping Beauty transposon vector for the generation of anti-CD117 CAR T cells incorporating an inducible Caspase 9 safety switch. The use of a non-viral technology to control CAR T-cell pharmacokinetic properties is attractive for a first-in-human study in patients with acute myeloid leukemia prior to hematopoietic stem cell transplantation.

Schematic outline depicting the study design of the clinical trial Magnani et al. Mol Ther Oncolytics 2023

Selected Publications (2022–2023)

The past, present, and future of non-viral CAR T cells. Moretti A, Ponzo M, Nicolette CA, Tcherepanova IJ, Biondi A, Magnani CF. Front. Immunol. 2022 Jun 9;13:867013

Genome Editing in Engineered T Cells for Cancer Immunotherapy. Chiara Bonini, Aude G. Chapuis, Michael Hudecek, Sonia Guedan, Chiara F. Magnani*, Waseem Qasim, and on Behalf of the Immunotherapy and CAR T Cells Scientific Committee of ESGCT. Hum Gene Ther. 2023 Sep;34(1718):853-869; *all authors share the first authorship

Anti-CD117 CAR T cells incorporating a safety switch eradicate human acute myeloid leukemia and hematopoietic stem cells. Magnani CF, Myburgh R, Brunn S, Chambovey M, Ponzo M, Volta L, Pellegrino C, Pascolo S, Miskey C, Ivics Z, Shizuru JA, Neri D, Manz MG. Mol Ther Oncolytics. 2023 Jul 19;30:56-71

Experimental Hematology and Immunology Lab

Keywords

Hematopoietic Stem Cells, Hematopoiesis, Hematopoietic Ageing, Hematopoietic Stem Cell Malignancies/Leukemia, Immunotherapy of Cancer

Aims

We aim to gain knowledge on healthy and malignant hematopoietic stem cells in order to develop new medical interventions for prevention and cure of hematopoietic stem cell disease. We develop and use engineered immunotherapies with the aim to fight hematopoietic and solid organ cancers more specifically and effectively.

Research Highlight

Ageing is associated with a state of low-grade inflammation, termed “Inflamm-Ageing”. We previously found that this is in large parts driven by the microbiome and IL-1 (Kovtonyuk et al., Blood 2022). We now demonstrate that increased bone marrow IL-1 levels during aging drive Tet2+/− premalignant clonal expansion via increased HSPC proliferation and multilineage differentiation. Genetic deletion of IL-1R1 abolishes, and, importantly, pharmacologic inhibition of IL-1–IL-1R1 signaling impairs, Tet2+/− clonal expansion during aging. This suggests that pharmacologic inhibition could prevent outgrowth of premalignant/pre-leukemia states.

Model of IL-1–mediated inflammageing as a driver of Tet2+/− clonal hematopoiesis. Working model on positive feedback loop driving development of aberrant Tet2+/− hematopoiesis induced by inflammaging-derived IL-1. Increased IL-1 levels derived from aged Tet2+/− mature myeloid cells act directly on HSPCs favoring Tet2+/− HSPC expansion (circular arrows), repopulation capacity, and multilineage differentiation (linear arrows) over WT HSPCs. IL-1–mediated Tet2+/− clonal expansion can be modulated by the administration of IL-1R1 antagonist (anakinra). Caiado et al. Blood 2023

Markus G. Manz

markus.manz@usz.ch

Research Group Members (A–Z)

– Francisco Caiado, PhD – Mara Hofstetter, PhD candidate – Anne Kaiser, MD – Francesco Manfredi, MD PhD

– Maddalena Marconato, MD PhD

– Monique Maurer, Technician – Jan Müller, MD – Renier Myburgh, PhD – Christian Pellegrino, PhD – Claudia Puig Moreno, PhD candidate – Gianluca Spaltro, MD PhD – Syndi Uhlig, Labmanager – Laura Volta, PhD – Matthias Wilk, MD

Funding

Selected Publications (2022–2023)

Anti-CD117 CAR T cells incorporating a safety switch eradicate human acute myeloid leukemia and hematopoietic stem cells. Magnani CF, Myburgh R, Brunn S, Chambovey M, Ponzo M, Volta L, Manfredi F, Pellegrino C, Pascolo S, Miskey C, Ivics Z, Shizuru JA, Neri D, Manz MG. Mol Ther Oncolytics. 2023 Jul 19;30:56-71

Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma. Kropivsek K, Kachel P, Goetze S, Wegmann R, Festl Y, Severin Y, Hale BD, Mena J, van Drogen A, Dietliker N, Tchinda J, Wollscheid B, Manz MG, Snijder B. Nat Cancer. 2023 May;4(5):734-753

Aging drives Tet2+/- clonal hematopoiesis via IL-1 signaling. Caiado F, Kovtonyuk LV, Gonullu NG, Fullin J, Boettcher S, Manz MG. Blood. 2023 Feb 23;141(8):886-903

Prognostic Value of FLT3-Internal Tandem Duplication Residual Disease in Acute Myeloid Leukemia. Grob T, Sanders MA, Vonk CM, Kavelaars FG, Rijken M, Hanekamp DW, Gradowska PL, Cloos J, Fløisand Y, van Marwijk Kooy M, Manz MG, Ossenkoppele GJ, Tick LW, Havelange V, Löwenberg B, Jongen-Lavrencic M, Valk PJM. J Clin Oncol. 2023 Feb 1;41(4):756-765

Addition of romiplostim to conditioning prior to HSCT allows chemotherapy reduction while maintaining engraftment levels. Wilk CM, Kovtonyuk LV, Manz MG. Blood Adv. 2022 Aug 9;6(15):44854489. d

Our research is supported by the Swiss National Science Foundation, the Krebsforschung Schweiz, Innosuisse, the Clinical Research Priority Program “ImmunoCure” of the University of Zurich, the Hochschulmedizin University of Zürich flagship program “ImmunoTargET”, “ImmunoCAR” (ZuriCAR) and Wyss Zürich.

César Nombela Arrieta cesar.nombelaarrieta@usz.ch

Research Group Members (A–Z)

– Candice Arnaud-Boissel, PhD candidate

– Paul Büschl, PhD candidate

– Serena Fazio, Msc

– Serena Galli, MD,

– YeVin Mun, Msc

– Angelina Oestmann, Dr. med. vet.

– Ana Luisa Pereira, MD

– Flavian Thelen, PhD

– Anjali Vijaykumar, Msc

Funding

Our research is supported by Swiss National Science Foundation, European Research Council Consolidator Grant program (ERC-CoG), Krebsforschung Schweiz, Clinical Research Priority Programs University of Zurich (CRPP), Novartis Foundation, Promedica Foundation, Krebsliga Zurich and Theodor-Egli Stiftung.

Experimental Hematology Lab

Keywords

Hematopoiesis, Bone Marrow Microenvironment, Hematopoietic Stem Cell Niche, 3D imaging, Malignancies

Aims

We aim to understand how the functional crosstalk of stromal, immune, and hematopoietic progenitor cells regulates hematopoiesis in health and disease. We have a special interest in defining how the tissue microenvironment of hematopoietic organs and hematopoietic stem cell niches are perturbed inflammatory conditions, infections, ageing and cancer, and how these alterations lead to hematological diseases.

Research Highlight

In collaboration with Prof. O. Goksel from the Computer Vision department of the ETH Zurich, we have recently developed novel computational models for the quantitative analysis of 3-dimensional images of bone marrow and fetal liver tissues. In combination of our experimental pipelines, these novel computational frameworks are being employed to quantitatively assess structural alterations and perturbations of spatial interactions that take place in the context of hematological malignancies and inflammatory conditions.

Quantification of spatial distributions in the bone marrow stroma (mesenchymal stromal cells in green, blood vessels in red and cyan) with our methods producing calibrated cell detections Gomariz et al. Science Advances 2022.

Selected Publications (2022–2023)

Probabilistic spatial analysis in quantitative microscopy with uncertainty-aware cell detection using deep Bayesian regression. Gomariz A, Portenier T, Nombela-Arrieta C, Goksel O. Science Advances. 2022 Feb 4;8(5):eabi8295

Hematopoietic Jagged1 is a fetal liver niche factor required for functional maturation and engraftment of fetal hematopoietic stem cells. Shao L, Paik NY, Sanborn MA, Bandara T, Vijaykumar A, Sottoriva K, Rehman J, Nombela-Arrieta C, Pajcini KV. Proc Natl Acad Sci U S A. 2023 May 16;120(20):e2210058120

Bone marrow haematopoiesis in patients with COVID-19. Marques-Maggio E, Maccio U, Marx A, Galli S, Schwab N, Frank A, Hamelin B, Varga Z, Nombela-Arrieta C, Mertz KD, Theocharides AP, Koelzer VH. Histopathology. 2023 Oct;83(4):582-590

B and T cell acute lymphoblastic leukemia evade chemotherapy at distinct sites in the bone marrow. Barz MJ, Behrmann L, Capron D, Zuchtriegel G, Steffen FD, Kunz L, Zhang Y, Vermeerbergen IJ, Marovca B, Kirschmann M, Zech A, Nombela-Arrieta C, Ziegler U, Schroeder T, Bornhauser B, Bourquin JP. Haematologica. 2022. May 1;108(5):1244-1258

Embryonic and neonatal waves generate distinct populations of hepatic ILC1s. Sparano C, SolísSayago D, Vijaykumar A, Rickenbach C, Vermeer M, Ingelfinger F, Litscher G, Fonseca A, Mussak C, Mayoux M, Friedrich C, Nombela-Arrieta C, Gasteiger G, Becher B, Tugues S. Sci Immunol. 2022 Sep 2;7(75):eabo6641

Leukemia Research and Cellular Therapies Lab

Keywords

Leukemia, Gene Editing, Tumorbiology, Targeted Therapies, Cellular Therapies, Hematopoietic Cell Transplantation, Graft-versus-Host Disease

Aims

We aim at understanding the mechanisms underlying malignant transformation of healthy hematopoietic stem and progenitor cells. Based on this, we develop novel targeted and immunotherapeutic treatment approaches against hematologic malignancies. We have a particular focus on hematopoietic cell transplantation and related side effects such as graft-versus-host disease.

Research Highlight

We establish novel human leukemia models by using CRIPSR/Cas9 gene editing to understand leukemogenesis and to use our platform to conduct high-throughput pharmaceutical studies.

We establish novel human leukemia models by using CRIPSR/Cas9 gene editing to understand leukemogenesis and to use our platform to conduct high-throughput pharmaceutical studies.

A

Generation of t(4;11)/t(9;11) cells using

B C

Immortalized t(4;11)/t(9;11) leukemic progenitor cells

(A) Scheme of generating CRISPR/Cas9 human leukemia models with indefinite in vitro growth potential.

(B) Transcriptomic profile of our models reveal different dysregulated signaling pathways as potential targets.

(C) Scheme of blocking the NOTCH1 pathway by CAD2004520. Fischer et al. IJMS. 2023

(A) Scheme of generating CRISPR/Cas9 human leukemia models with indefinite in vitro growth potential. (B) Transcriptomic profile of our models reveal different dysregulated signaling pathways as potential targets. (C) Scheme of blocking the NOTCH1 pathway by CAD2004520. Fischer et al. International Journal of Molecular Sciences 2023

Selected Publications (2022–2023)

Uncovering NOTCH1 as a Promising Target in the Treatment of MLL-Rearranged Leukemia. Fischer J, Erkner E, Fitzel R, Radszuweit P, Keppeler H, Korkmaz F, Roti G, Lengerke C, Schneidawind D, Schneidawind C. Int J Mol Sci. 2023, 24(19):14466

Targeting MYC in combination with epigenetic regulators induces synergistic anti-leukemic effects in MLLr leukemia and simultaneously improves immunity. Fitzel R, Secker-Grob KA, Keppeler H, Korkmaz F, Schairer R, Erkner E, Schneidawind D, Lengerke C, Hentrich T, Schulze-Hentrich JM, Schneidawind C. Neoplasia. 2023 Jul, 41:100902

Low Graft Invariant Natural Killer T-Cell Dose Is a Risk Factor for Cytomegalovirus Reactivation After Allogeneic Hematopoietic Cell Transplantation Schneidawind D, Duerr-Stoerzer S, Liewer S, Renner S, Sánchez Navarro B, Atar D, Keppeler H, Beck R, Hamprecht K, Kanz L, Lengerke C, Schneidawind C. Transplant Cell Ther. 2022, 28(8):513.e1-513.e4

iNKT cells can effectively inhibit IL-6 production by B cells in systemic sclerosis. Einhaus J, Asteriti E, Pecher AC, Keppeler H, Klein R, Schneidawind C, Henes J, Schneidawind D. Cytotherapy. 2022, 24(5):482-488

Human invariant natural killer T cells promote tolerance by preferential apoptosis induction of conventional dendritic cells. Schmid H, Ribeiro EM, Secker KA, Duerr-Stoerzer S, Keppeler H, Dong R, Munz T, Schulze-Osthoff K, Hailfinger S, Schneidawind C, Schneidawind D. Haematologica. 2022, 107(2):427-436

Corina and Dominik Schneidawind corina.schneidawind@usz.ch dominik.schneidawind@usz.ch

Research Group Members (A–Z) – Alvaro Menchaca Muniz, PhD candidate – Aleksei Parshenkov, PhD – Pia Radszuweit, PhD candidate

Funding German Research Foundation, German Cancer Aid, José Carreras Leukemia Foundation, Iten Kohaut Foundation, SNF, GeistlichStucki Foundation, Gilead Swiss Fellowship.

Human cord blood

Notch1 signaling pathway

Isolation of CBMCs Magnetic cell separation of CD34+ HSPCs

Culturing of HSPCs for 48 h

HSPCs

CRISPR/Cas9

Cell culture of CB MLL-AF4 / CB MLL-AF9

Jan-Dirk Studt

jandirk.studt@usz.ch

Coagulation/Platelet Disorders

Keywords

Thrombotic microangiopathies/thrombotic thrombocytopenic purpura (TTP), direct oral anticoagulants (DOAC), heparin-induced thrombocytopenia (HIT)

Aims

We aim to understand (1) the treatment of immune and congenital TTP, (2) perioperative bleeding risk and laboratory monitoring of DOAC, (3) diagnosis of HIT, and (4) platelet structure in congenital platelet disorders.

Research Highlight:

We investigated first time the efficacy and safety of the anti-CD38 antibody daratumumab for refractory and frequently relapsing immune thrombotic thrombocytopenic purpura (iTTP). We demonstrated a rapid clearance of anti-ADAMTS13 autoantibodies and normalization of deficient ADAMTS13 activity following daratumumab. No relevant adverse effects were observed. Daratumumab could therefore be a safe and efficacious option for refractory and frequently relapsing iTTP.

Treatment of iTTP with the anti-CD38 antibody daratumumab. Clinical course and selected laboratory parameters in 2 patients. (A) Patient 1 with frequently relapsing iTTP 8latest iTTP relapse shown); (B) Patient 2 with a refractory first iTTP episode. Red line = titer of ADAMTS13 inhibitor; blue line = ADAMTS13 activity; gray line = platelet count. Van den Berg J et al. Blood Adv. 2022

Selected Publications (2022–2023)

Daratumumab for immune thrombotic thrombocytopenic purpura. Van den Berg J, Kremer Hovinga JA, Pfleger C, Hegemann I, Stehle G, Holbro A, Studt JD. Blood Adv. 2022; 6: 993-997

Platelets drive fibronectin fibrillogenesis using IIb3. Lickert S, Kenny M, Selcuk K, Mehl JL, Bender M, Früh SM, Burckhardt MA, Studt JD, Nieswandt B, Schoen I, Vogel V. Sci Adv. 2022; 8: eabj8331

A machine-learning model for reducing misdiagnosis in heparin-induced thrombocytopenia: a prospective, multicenter, observational study. Nilius H, Cuker A, Haug S, Nakas C, Studt JD, Tsakiris DA, Greinacher A, Mendez A, Schmidt A, Wuillemin WA, Gerber B, Kremer Hovinga JA, Vishnu P, Graf L, Kashev A, Sznitman R, Bakchoul T, Nagler M. EClinicalMedicine. 2022; 55: 101745

Limited concordance of heparin/platelet factor 4 antibody assays for the diagnosis of heparin-induced thrombocytopenia: an analysis of the TORADI-HIT study. Hammerer-Lercher A, Nilius H, Studt JD, Tsakiris DA, Greinacher A, Mendez A, Schmidt A, Wuillemin WA, Gerber B, Kremer Hovinga JA, Vishnu P, Graf L, Bakchoul T, Nagler M. J Thromb Haemost. 2023; 21: 2559-2568

Translational Hematology Lab

Keywords

Calreticulin, Myeloproliferative Neoplasms, Macrophage Immune Checkpoints, CD47, Immunotherapy

Aims

We are interested in the molecular mechanisms that contribute to myeloproliferative neoplasms, in particular mutations in the chaperone calreticulin. Another area of interest is the role of macrophage immune checkpoints in myeloid neoplasms.

Research Highlight

We performed a drug screening study in patients with myeloproliferative neoplasms. The peripheral blood of patients was exposed to a drug library and visualized by microscopy (pharmacoscopy) in collaboration with Prof. B. Snijder (ETHZ). Thereafter, an antibody specific to calreticulin (CALR) mutant cells was used to assess the response of CALR mutant cells to a drug. We show that CALR mutated cells are particularly sensitive to the inhibition of bromodomain and extra-terminal motif (BET) proteins.

CALR mutant cells identified by a mutant-specific antibody (red) are targeted by BET inhibitor treatment. In comparison cells, which do not carry the mutation or lack CALR are not affected. Wildschut et al. Nat Commun. 2023

Selected Publications (2022–2023)

Ruxolitinib in patients with polycythemia vera resistant and/or intolerant to hydroxyurea: European. Observational study. Theocharides A, Gisslinger H, De Stefano V, Accurso V, Iurlo A, Devos T, Egyed M, Lippert E, Delgado RG, Cantoni N, Dahm AEA, Sotiropoulos D, Houtsma E, Smyth A, Iqbal A, Di Matteo P, Zuurman M, Te Boekhorst PAW. Eur J Haematol. 2023 Oct 30. doi: 10.1111/ejh.14124. Online ahead of print

Proteogenetic drug response profiling elucidates targetable vulnerabilities of myelofibrosis. Wildschut M, Mena J, Dördelmann C, van Oostrum M, Hale B, Settelmeier J, Festl Y, Lysenko V, Schürch P, Ring A, Severin Y, Bader M, Pedrioli P, Goetze S, van Drogen A, Balabanov S, Skoda R, Lopes M, Wollscheid B*, Theocharides A*, Snijder B* (*Shared last authorship. Nat Commun. 2023 Oct 12;14(1):6414.)

Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms. Grockowiak E, Korn C, Rak J, Lysenko V, Hallou A, Panvini FM, Williams M, Fielding C, Fang Z, Khatib-Massalha E, García-García A, Li J, Khorshed RA, González-Antón S, Baxter EJ, Kusumbe A, Wilkins BS, Green A, Simons BD, Harrison CN, Green AR, Lo Celso C, Theocharides A, Méndez-Ferrer S. Nat Cancer. 2023 Aug;4(8):1193-1209

Blocking the CD47-SIRPα interaction reverses the disease phenotype in a polycythemia vera mouse model. Lysenko V, Schürch P, Tuzlak S, Wildner-Verhey van Wijk N, Kovtonyuk L, Becher, B, Manz MG, Kreutmair S, and Theocharides A. Leukemia. 2023 Jun;37(6):1277-1286

Calreticulin mutations affect its chaperone function and perturb the glycoproteome. Schürch P, Malinovska L, Hleihil M, Losa M, Hofstetter MC, Wildschut MHE, Lysenko V, Lakkaraju AKK, Maat CA, Benke D, Aguzzi A, Wollscheid B, Picotti P, Theocharides A. Cell Rep. 2022 Nov 22;41(8):111689

Alexandre Theocharides alexandre.theocharides@usz.ch

Research Group Members (A–Z) – Lisa Dietsche, PhD – Riikka Kivioja, PhD – Stefanie Kreutmair, MD – Veronika Lysenko, PhD – Dinh-Van Vuong – Thijs Wildschut, PhD

Funding Our research is supported by the Swiss National Science Foundation, the Swiss Cancer League, and the UZH Clinical Research Priority Program Precision Hematology/ Oncology.

Andreas Wicki andreas.wicki@usz.ch

Research Group Members (A–Z)

– Laura Boos, MD – Elija Brunschwiler, physician – Fabregas-Ibanez Luis, PhD – Benedict Gosztonyi, MD – Gabriele Gut, PhD – Danny Kupka, MD – Tarun Mehra, MD – Nicola Miglino, PhD – Parisa Rahimzadeh, PhD cand.

– Alexander Ring, MD, PhD – Manuel Schürch, PhD

Funding

Our research is supported by the Swiss National Science Foundation, the strategic focus area of Personalized Health & Related Technologies ETH Zurich, the Swiss Personalized Oncology National Data Stream, the Swiss Cancer League, the Swiss Foundation for Clinical Cancer Research (SSKK), the Promedica Foundation, the Hoschschulmedizin “Tumor Profiler Center” project, and the University of Zurich.

Experimental Oncology Lab

Keywords

Oncology, Precision Medicine, Therapy Prediction with Novel AI-Based Approaches, Functional and Multi-Omics Testing

Aims

The Experimental Oncology Research Group has a focus on improving therapy outcomes in oncology by combining deep analysis of tumor tissue (functional & single cellomics) with state-of-the-art data science. Using modern analytical platforms, several tens of thousands of tumor attributes can be assessed from a little piece of tissue within around two weeks. This significant technological progress has paved the way to make multiomics approaches usable for individual therapy prediction in a clinical setting. By connecting deep biological analysis with large clinical databases (including Real World Data), modelling of therapy response and benefit is possible with an unprecedented accuracy.

Research Highlight

There is evidence for a possible link between immune-related adverse events (irAEs) and checkpoint-inhibitor treatment efficacy. Development of irAEs has been associated with improved survival in patients receiving immune checkpoint inhibitors. We wanted to assess the effect of irAEs on survival in a large, real-life patient cohort treated with immune checkpoint inhibitors for multiple tumor entities. We found an independent association between irAE occurrence and improved overall survival in a real-life cohort spanning multiple tumor entities and treatment regimens. Furthermore, we identified pre-treatment comorbidities, C-reactive protein, and eosinophil count as predictors of survival with checkpoint inhibition.

Kaplan–Meier survival curves of patients with (green line) and without (blue line) immune-related adverse events (irAE) during checkpoint-inhibitor treatment (N = 229). Log-rank p = 0.006, hazard ratio 0.58 (95% CI 0.40–0.83). Mehra et al. Cancer Med. 2023

Selected Publications (2022–2023)

A multicenter phase II trial of anti-EGFR-immunoliposomes loaded with doxorubicin in patients with advanced triple negative breast cancer. Mamot C, Wicki A, Hasler-Strub U, Riniker S, Li Q, Holer L, Bärtschi D, Zaman K, von Moos R, Dedes KJ, Boos LA, Novak U, Bodmer A, Ritschard R, Obermann EC, Tzankov A, Ackermann C, Membrez-Antonioli V, Zürrer-Härdi U, Caspar CB, Deuster S, Senn M, Winterhalder R, Rochlitz C. Sci Rep. 2023 Mar 6;13(1):3705

Pre-treatment comorbidities, C-reactive protein and eosinophil count, and immune-related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities. Mehra T, Dongre K, Boesing M, Frei P, Suenderhauf C, Zippelius A, Leuppi JD, Wicki A, Leuppi-Taegtmeyer AB. Cancer Med. 2023 Jun;12(11):12253-12262

Biology, vulnerabilities and clinical applications of circulating tumour cells. Ring A, Nguyen-Sträuli BD, Wicki A, Aceto N. Nat Rev Cancer. 2023 Feb;23(2):95-111

Structure-based prediction of BRAF mutation classes using machine-learning approaches. Krebs FS, Britschgi C, Pradervand S, Achermann R, Tsantoulis P, Haefliger S, Wicki A, Michielin O, Zoete V. Sci Rep. 2022 Jul 22;12(1):12528

MyCTC chip: microfluidic-based drug screen with patient-derived tumour cells from liquid biopsies. Schwab FD, Scheidmann MC, Ozimski LL, Kling A, Armbrecht L, Ryser T, Krol I, Strittmatter K, Nguyen-Sträuli BD, Jacob F, Fedier A, Heinzelmann-Schwarz V, Wicki A, Dittrich PS, Aceto N. Microsyst Nanoeng. 2022 Dec 20;8:130

Lymphoma Research Lab

Keywords

Precision Medicine, CLL, Drug Screening, Omics Profiling, Functional Genomics

Aims

To develop rational and biology-based ways for patient benefit from advances in molecular understanding and targeted drug treatment, we pursue an innovative strategy based on the comprehensive mapping and understanding of individual cancers’ vulnerability to compounds, pathway inhibitors and drugs as well as genome-wide silencing triggers (RNAi, CRISPR). We classify disease based on pathway sensitivity and the systematic understanding of underlying molecular networks on bulk and single-cell level.

Research Highlight

Subgroup-specific gene expression profiles and mixed epistasis in chronic lymphocytic leukemia. Understanding the molecular and phenotypic heterogeneity of cancer is a prerequisite for effective treatment. For chronic lymphocytic leukemia (CLL), recurrent genetic driver events have been extensively cataloged, but this does not suffice to explain the disease’s diverse course. We performed RNA sequencing on 184 CLL patient samples. Unsupervised analysis revealed two major, orthogonal axes of gene expression variation. We discovered non-additive effects (epistasis) of IGHV mutation status and trisomy 12 on multiple phenotypes, including the expression of 893 genes. Multiple types of epistasis were observed, including synergy, buffering, suppression and inversion, suggesting that molecular understanding of disease heterogeneity requires studying such genetic events not only individually but in combination. Our study reveals previously underappreciated gene expression signatures for the major molecular subtypes in CLL and the presence of epistasis between them.

Selected Publications (2022–2023)

Gene expression variability in chronic lymphocytic leukemia.

Lütge et al. Haematologica 2023

Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial. Liebers N, Bruch PM, Terzer T, Hernandez-Hernandez M, Paramasivam N, Fitzgerald D, Altmann H, Roider T, Kolb C, Knoll M, Lenze A, Platzbecker U, Röllig C, Baldus C, Serve H, Bornhäuser M, Hübschmann D, Müller-Tidow C, Stölzel F, Huber W, Benner A, Zenz T, Lu J, Dietrich S. Nat Cancer. 2023 Dec;4(12):1648-1659

Subgroup-specific gene expression profiles and mixed epistasis in chronic lymphocytic leukemia. Lütge A, Lu J, Hüllein J, Walther T, Sellner L, Wu B, Rosenquist R, Oakes CC, Dietrich S, Huber W, Zenz T. Haematologica. 2023 Oct 1;108(10):2664-2676

Inferring tumor-specific cancer dependencies through integrating ex vivo drug response assays and drug-protein profiling. Batzilla A, Lu J, Kivioja J, Putzker K, Lewis J, Zenz T, Huber W. PLoS Comput Biol. 2022 Aug 22;18(8):e1010438. doi: 10.1371/journal.pcbi.1010438. eCollection 2022 Aug

Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL. Bruch PM, Giles HA, Kolb C, Herbst SA, Becirovic T, Roider T, Lu J, Scheinost S, Wagner L, Huellein J, Berest I, Kriegsmann M, Kriegsmann K, Zgorzelski C, Dreger P, Zaugg JB, Müller-Tidow C, Zenz T, Huber W, Dietrich S. Mol Syst Biol. 2022 Aug;18(8):e10855

SHMT2 inhibition disrupts the TCF3 transcriptional survival program in Burkitt lymphoma. Wilke AC, Doebele C, Zindel A, Lee KS, Rieke SA, Ceribelli M, Comoglio F, Phelan JD, Wang JQ, Pikman Y, Jahn D, Häupl B, Schneider C, Scheich S, Tosto FA, Bohnenberger H, Stauder P, Schnütgen F, Slabicki M, Coulibaly ZA, Wolf S, Bojarczuk K, Chapuy B, Brandts CH, Stroebel P, Lewis CA, Engelke M, Xu X, Kim H, Dang TH, Schmitz R, Hodson DJ, Stegmaier K, Urlaub H, Serve H, Schmitt CA, Kreuz F, Knittel G, Rabinowitz JD, Reinhardt HC, Vander Heiden MG, Thomas C, Staudt LM, Zenz T, Oellerich T. Blood. 2022 Jan 27;139(4):538-553

Thorsten Zenz thorsten.zenz@usz.ch lymphomaresearchzurich.com

Research Group Members (A–Z)

– Jan Lukas Bögeholz, MD – Ester Cannizzaro, PhD – Nadia Djerbi, MD – Thi Huong Lan Do, PhD candidate – Odit Gutwein, MD/Visiting physicianscientist – Jarno Kivioja, PhD (Visiting scientist)

– Stefanie Kreutmair, MD – Sandra Kummer, Biomed. Analyst – Marcel Pohly, MD candidate – Stefanie Reisenauer, PhD candidate – Rosary Yao, PhD candidate

Funding Our research is supported by The Loop Zurich, Krebsliga, Promedica, Leukemia Lymphoma Society, UZH CRPP, and CCCZ.

Awards and Fellowships

Awards 2022

Christian Koch

Competitive research grants from the EMDO-Stiftung and Theodor und Ida Herzog-Egli-Stiftung to support his research project “From clonal hematopoiesis to therapy-related myeloid neoplasms”.

Alexander Ring

Siegenthaler Foundation research stipend for his project “Establishing a translational liquid biopsy platform for biomarker discovery and therapeutic targeting of micrometastatic dormancy in breast cancer”.

Jan Müller

DGHO Poster prize for his work on “Resistance mechanisms of CAR T cells in the context of TP53-mutant AML”.

Max Rieger & Rahel Schwotzer

SOHC Best Abstract Award in Supportive Care for their work on “Catheter-related complications in the context of systemic anticancer treatment”.

Roman Schimmer

Prix Ellermann Relève en Hématologie of the Swiss Society for Hematology for his work on “TP53-mutant myeloid malignancies”.

Flavian Thelen

Kick-off grant from the European Hematology Association (EHA) for his project “Regulation of Hematopoietic Stem Cells by Bone Marrow Memory CD8 T Cells”.

Awards 2023

Francisco Caiado

Ida de Pottère-Leupold and Dr. iur. Erik de Pottère Cancer Research Award for postdoctoral scientists for his work “Aging drives Tet2+/− clonal hematopoiesis via IL-1 Signaling”.

Francesco Manfredi

Ellermann Young Talent Award in Hematology - SGHSSH (at SOHC).

Max Rieger

SAKK-Pfizer Prize (at SOHC) for patient-oriented clinical cancer research.

César Nombela-Arrieta

Ellermann Award - SGH-SSH (at SOHC).

Parisa Rahmizadeh

SOHC Poster Prize for the project “Supportive & Palliative care, Rehabiliation & Survivorship”.

Fellowships 2022/2023

Kevin Hofer

Jacques and Gloria Gossweiler Foundation Research Fellowship Award (at SOHC).

Ana Luisa Marques

Candoc-fellowship for the project “Understanding the effects of acute myeloid leukemia on the bone marrow microenvironment”.

Wiebke Rösler and Jeremy Deuel Competitive two-year Promedica grants.

Flavian Thelen

UZH Postdoc-fellowship for the project “Dissection of the role of memory T cells on HSC maintenance”.

Publications

2022

Koch, Christian A; Fischer, Nina Charlotte; Puchert, Malte; Engele, Jürgen (2022). Interactions of the chemokines CXCL11 and CXCL12 in human tumor cells. BMC Cancer, 22:1335.

Akhoundova, Dilara; Hussung, Saskia; Sivakumar, Smruthy; Töpfer, Antonia; Rechsteiner, Markus; Kahraman, Abdullah; Arnold, Fabian; Angst, Florian; Britschgi, Christian; Zoche, Martin; Moch, Holger; Weber, Achim; Sokol, Ethan; Fritsch, Ralph M (2022). ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer. International Journal of Cancer, 151(12):2161-2171.

Ravandi, Farhad; Kreitman, Robert J; Tiacci, Enrico; et al; Zenz, Thorsten (2022). Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia. Blood Cancer Journal, 12(12):165.

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Le, Xiuning; Sakai, Hiroshi; Felip, Enriqueta; Veillon, Remi; Garassino, Marina Chiara; et al; Britschgi, Christian (2022). Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice. Clinical Cancer Research, 28(6):11171126.

Meloni, Claudia; Schreiber, Cornelia; Studt, Jan-Dirk; Kamm, Simone; Di Chiara, Manuela; Herren, Thomas (2022). Liver infarctions as the first manifestation of antiphospholipid antibody syndrome in pregnancy: a case report. Journal of Medical Case Reports, 16:103.

Lickert, Sebastian; Kenny, Martin; Selcuk, Kateryna; Mehl, Johanna L; Bender, Markus; Früh, Susanna M; Burkhardt, Melanie A; Studt, Jan-Dirk; Nieswandt, Bernhard; Schoen, Ingmar; Vogel, Viola (2022). Platelets drive fibronectin fibrillogenesis using integrin α IIb β 3. Science Advances, 8(10):eabj8331.

Zapatka, Marc; Tausch, Eugen; Öztürk, Selcen; Yosifov, Deyan Yordanov; Seiffert, Martina; Zenz, Thorsten; Schneider, Christof; Blöhdorn, Johannes; Döhner, Hartmut; Mertens, Daniel; Lichter, Peter; Stilgenbauer, Stephan (2022). Clonal evolution in chronic lymphocytic leukemia is scant in relapsed but accelerated in refractory cases after chemo(immune)therapy. Haematologica, 107(3):604614.

Schlagenhauf, Patricia; Deuel, Jeremy (2022). Concerts and COVID: can the beat go on? Lancet Infectious Diseases, 22(3):299301.

Schulze, Jan Ben; Günther, Moritz Philipp; Riemenschnitter, Cosima; Wicki, Andreas; von Känel, Roland; Euler, Sebastian (2022). Distinct psycho-oncological support inclinations and needs in patients with cancer: A large sample latent class analysis approach. General Hospital Psychiatry, 75:17-22.

Schrader, Markus; Oberkofler, Christian Eugen; Pietge, Heike; Pavic, Matea; Petrowsky, Henrik; Guckenberger, Matthias; Garcia Schueler, Helena Isabel (2022). Stereotactic Irradiation of the Pancreas: Case Study of a Patient With Persistent Pancreatic Fistula. Pancreas, 51(3):e62-e63.

Malehmir, Mohsen; Pfister, Dominik; Gallage, Suchira; Szydlowska, Marta; Inverso, Donato; Kotsiliti, Elena; Leone, Valentina; Peiseler, Moritz; Surewaard, Bas G J; Rath, Dominik; Ali, Adnan; Wolf, Monika Julia; Drescher, Hannah; Healy, Marc E; Dauch, Daniel; Kroy, Daniela; Krenkel, Oliver; Kohlhepp, Marlene; Engleitner, Thomas; Olkus, Alexander; Sijmonsma, Tjeerd; Volz, Julia; Deppermann, Carsten; Stegner, David; Helbling, Patrick; Nombela-Arrieta, César; Rafiei, Anahita; Hinterleitner, Martina; Rall, Marcel; Baku, Florian; Weber, Achim; et al (2022). Author Correction: Platelet GPIb α is a mediator and potential interventional target for NASH and subsequent liver cancer. Nature Medicine, 28(3):600.

Brezina, T; von Dewitz, H; Schroeder, T; Ullrich, S; Nachtkamp, K; Reifenberger, G; Malzkorn, B; Sabel, M; Haas, R; Kobbe, G (2022). First-line high-dose therapy and autologous blood stem cell transplantation in patients with primary central nervous system non-Hodgkin lymphomas-a single-centre experience in 61 patients. Annals of Hematology, 101(3):607-616.

Tamò, Raphaël; Turk, Teja; Böni, Jürg; Kouyos, Roger D; Schmutz, Stefan; Huber, Michael; Shah, Cyril; Bischoff-Ferrari, Heike A; Distler, Oliver; Battegay, Edouard; Giovanoli, Pietro; Guckenberger, Matthias; Kohler, Malcolm; Müller, Rouven; Petry, Heidi; Ruschitzka, Frank; McGeer, Allison; Sax, Hugo; Weber, Rainer; Trkola, Alexandra; Kuster, Stefan P (2022). Secondary attack rates from asymptomatic and symptomatic influenza virus shedders in hospitals: Results from the TransFLUas influenza transmission study. Infection Control and Hospital Epidemiology, 43(3):312-318.

Van den Berg, Jana; Kremer Hovinga, Johanna A; Pfleger, Claudia; Hegemann, Inga; Stehle, Gregor Thomas; Holbro, Andreas; Studt, Jan-Dirk (2022). Daratumumab for immune thrombotic thrombocytopenic purpura. Blood Advances, 6(3):993-997.

Gomariz, Alvaro; Portenier, Tiziano; Nombela-Arrieta, César; Goksel, Orcun (2022). Probabilistic spatial analysis in quantitative microscopy with uncertainty-aware cell detection using deep Bayesian regression. Science Advances, 8(5):eabi8295.

Caiado, Francisco; Manz, Markus G (2022). A microbiome-macrophage-iron axis guides stressed hematopoietic stem cell fate. Cell Stem Cell, 29(2):177-179.

Bonfiglio, Ferdinando; Bruscaggin, Alessio; Guidetti, Francesca; Terzi di Bergamo, Lodovico; Faderl, Martin; Spina, Valeria; Condoluci, Adalgisa; Bonomini, Luisella; Forestieri, Gabriela; Koch, Ricardo; Piffaretti, Deborah; Pini, Katia; Pirosa, Maria Cristina; Cittone, Micol Giulia; Arribas, Alberto; Lucioni, Marco; Ghilardi, Guido; Wu, Wei; Arcaini, Luca; et al; Elia, Angela Rita; Calcinotto, Arianna; Ceriani, Luca; Cogliatti, Sergio; Gerber, Bernhard; Zenz, Thorsten; Moccia, Alden; Stathis, Anastasios (2022). Genetic and phenotypic attributes of splenic marginal zone lymphoma. Blood, 139(5):732747.

Krieg, Stefan; Seeger, Harald; Hofmann, Patrick; Del Prete, Carmen; Manz, Markus G; Müller, Antonia M; Theocharides, Alexandre P A (2022). Baseline creatinine predicts acute kidney injury during intensive therapy in transplant-eligible patients with acute myeloid leukaemia. British Journal of Haematology, 196(3):781-784.

Eshmuminov, Dilmurodjon; Hefti, Max; Mueller, Matteo; Schuler, Martin J; Bautista Borrego, Lucia; Schneider, Marcel André; Koch, Karin; Weisskopf, Miriam; Tibbitt, Mark W; Dutkowski, Philipp; Rudolf von Rohr, Philipp; Studt, Jan-Dirk; Becker, Dustin; Clavien, Pierre-Alain (2022). Synthesis of coagulation factors during long-term ex situ liver perfusion. Artificial Organs, 46(2):273-280.

Bakunina, Katerina; Putter, Hein; Versluis, Jurjen; Koster, Eva A S; van der Holt, Bronno; Manz, Markus G; Breems, Dimitri A; Gjertsen, Bjorn T; Cloos, Jacqueline; Valk, Peter J M; Passweg, Jakob; Pabst, Thomas; Ossenkoppele, Gert J; Löwenberg, Bob; Cornelissen, Jan J; de Wreede, Liesbeth C (2022). The added value of multi-state modelling in a randomized controlled trial: The HOVON 102 study re-analyzed. Cancer Medicine, 11(3):630-640.

Soo, R A; Han, J-Y; Dafni, U; Cho, B C; Yeo, C M; et al; Britschgi, Christian (2022). A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial. Annals of Oncology, 33(2):181-192.

Fehr, Thomas; Hübel, Kerstin; de Rougemont, Olivier; Abela, Irene; Gaspert, Ariana; Güngör, Tayfun; Hauri, Mathias; Helmchen, Birgit; Linsenmeier, Claudia; Müller, Thomas; Nilsson, Jakob; Riesterer, Oliver; Scandling, John D; Schanz, Urs; Cippà, Pietro E (2022). Successful Induction of Specific Immunological Tolerance by Combined Kidney and Hematopoietic Stem Cell Transplantation in HLA-Identical Siblings. Frontiers in Immunology, 13:796456.

Wilke, Anne C; Doebele, Carmen; Zindel, Alena; et al; Zenz, Thorsten (2022). SHMT2 inhibition disrupts the TCF3 transcriptional survival program in Burkitt lymphoma. Blood, 139(4):538-553.

Pavic, Matea; Niyazi, M; Wilke, Lotte; Corradini, Stefanie; Vornhülz, M; Mansmann, U; Al Tawil, A; Fritsch, Ralph; Hörner-Rieber, J; Debus, J; Guckenberger, Matthias; Belka, Claus; Mayerle, J; Beyer, G (2022). MR-guided adaptive stereotactic body radiotherapy (SBRT)

of primary tumor for pain control in metastatic pancreatic ductal adenocarcinoma (mPDAC): an open randomized, multicentric, parallel group clinical trial (MASPAC). Radiation Oncology, 17:18.

Fiskus, Warren; Boettcher, Steffen; Daver, Naval; Mill, Christopher P; Sasaki, Koji; Birdwell, Christine E; Davis, John A; Takahashi, Koichi; Kadia, Tapan M; DiNardo, Courtney D; Jin, Qi; Qi, Yuan; Su, Xiaoping; McGeehan, Gerard M; Khoury, Joseph D; Ebert, Benjamin L; Bhalla, Kapil N (2022). Effective Menin inhibitor-based combinations against AML with MLL rearrangement or NPM1 mutation (NPM1c). Blood Cancer Journal, 12(1):5.

Zarotti, Cristina; Papassotiropoulos, Bärbel; Elfgen, Constanze; Dedes, Konstantin; Vorburger, Denise; Pestalozzi, Bernhard; Trojan, Andreas; Varga, Zsuzsanna (2022). Biomarker dynamics and prognosis in breast cancer after neoadjuvant chemotherapy. Scientific Reports, 12:91.

Kovtonyuk, Larisa Vladimirovna; Caiado, Francisco; Garcia-Martin, Santiago; Manz, Eva-Maria; Helbling, Patrick Michael; Takizawa, Hitoshi; Boettcher, Steffen; Al-Shahrour, Fatima; Nombela-Arrieta, Cesar; Slack, Emma; Manz, Markus G (2022). IL-1 Mediates Microbiome-Induced Inflamm-Ageing of Hematopoietic Stem Cells in Mice. Blood, 139(1):44-58.

Voglis, Stefanos; Yildiz, Yesim; von Faber-Castell, Fabio; Harnisch, Kim Jannis; Regli, Luca; Bellut, David; Schwotzer, Rahel; Germans, Menno R (2022). Surgically treated intradural spinal manifestation of hereditary amyloidogenic transthyretin amyloidosis - A case report and scoping review of the literature. Brain and Spine, 2:100876.

Skawran, Stephan; Gennari, Antonio G; Dittli, Manuel; Treyer, Valerie; Muehlematter, Urs J; Maurer, Alexander; Burger, Irene A; Mader, Cäcilia; Messerli, Olivia; Grünig, Hannes; Gebhard, Catherine; Huellner, Martin W; Curioni-Fontecedro, Alessandra; Berger, Christoph; Messerli, Michael (2022). [ 18 F]FDG uptake of axillary lymph nodes after COVID-19 vaccination in oncological PET/CT: frequency, intensity, and potential clinical impact. European Radiology, 32(1):508-516.

Peters, S; Pujol, J-L; Dafni, U; Dómine, M; Popat, S; Reck, M; Andrade, J; Becker, A; Moro-Sibilot, D; Curioni-Fontecedro, A; Molinier, O; Nackaerts, K; Insa Mollá, A; Gervais, R; López Vivanco, G; Madelaine, J; Mazieres, J; Faehling, M; Griesinger, F; Majem, M; González Larriba, J L; Provencio Pulla, M; Vervita, K; Roschitzki-Voser, H; Ruepp, B; Mitchell, P; Stahel, R A; Le Pechoux, C; De Ruysscher, D (2022). Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy - results from the randomised phase II ETOP/ IFCT 4-12 STIMULI trial. Annals of Oncology, 33(1):67-79.

Cathomas, Richard; Lorch, Anja; Bruins, Harman M; Compérat, Eva M; Cowan, Nigel C; Efstathiou, Jason A; Fietkau, Rainer; Gakis, Georgios; Hernández, Virginia; Espinós, Estefania Linares; Neuzillet, Yann; Ribal, Maria J; Rouanne, Matthieu; Thalmann, George N; van der Heijden, Antoine G; Veskimäe, Erik; Alfred Witjes, J; Milowsky, Matthew I (2022). The 2021 Updated European Association of Urology Guidelines on Metastatic Urothelial Carcinoma. European Urology, 81(1):95-103.

Meihandoest, Tamana; Studt, Jan-Dirk; Mendez, Adriana; Alberio, Lorenzo; Fontana, Pierre; Wuillemin, Walter A; Schmidt, Adrian; Graf, Lukas; Gerber, Bernhard; Amstutz, Ursula; Bovet, Cédric; Sauter, Thomas C; Asmis, Lars M; Nagler, Michael (2022). Accuracy of a Single, Heparin-Calibrated Anti-Xa Assay for the Measurement of Rivaroxaban, Apixaban, and Edoxaban Drug Concentrations: A Prospective Cross-Sectional Study. Frontiers in cardiovascular medicine, 9:817826.

Meloni, Claudia. Characterization of a single center acute myeloid leukemia patient cohort treated with an intensive regimen. 2022, University of Zurich, Medizinische Fakultät.

Ring, Alexander; Spataro, Maria; Wicki, Andreas; Aceto, Nicola (2022). Clinical and Biological Aspects of Disseminated Tumor Cells and Dormancy in Breast Cancer. Frontiers in Cell and Developmental Biology, 10:929893.

Bischoff-Ferrari, Heike A; Willett, Walter C; Manson, JoAnn E; Dawson-Hughes, Bess; Manz, Markus G; Theiler, Robert; Braendle, Kilian; Vellas, Bruno; Rizzoli, René; Kressig, Reto W; Staehelin, Hannes B; da Silva, José A P; Armbrecht, Gabriele; Egli, Andreas; Kanis, John A; Orav, Endel J; Gaengler, Stephanie (2022). Combined Vitamin D, Omega-3 Fatty Acids, and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial. Frontiers in Aging, 3:852643.

Tettero, Jesse M; Al-Badri, Waleed K W; Ngai, Lok Lam; Bachas, Costa; Breems, Dimitri A; van Elssen, Catharina H M J; Fischer, Thomas; Gjertsen, Bjorn T; van Gorkom, Gwendolyn N Y; Gradowska, Patrycja; Greuter, Marjolein J E; Griskevicius, Laimonas; Juliusson, Gunnar; Maertens, Johan; Manz, Markus G; Pabst, Thomas; Passweg, Jakob; Porkka, Kimmo; Löwenberg, Bob; Ossenkoppele, Gert J; Janssen, Jeroen J W M; Cloos, Jacqueline (2022). Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis. Frontiers in Oncology, 12:999822.

Šuipytė, Jorūnė. Does progress achieved in treatment of patients with metastatic non-small-cell lung cancer (NSCLC) reach the elderly population? 2022, University of Zurich, Medizinische Fakultät.

Christiansen, Ailsa J; Lobo, João; Fankhauser, Christian Daniel; Rothermundt, Christian; Cathomas, Richard; Batavia, Aashil A; Grogg, Josias B; Templeton, Arnoud J; Hirschi-Blickenstorfer, Anita; Lorch, Anja; Gillessen, Silke; Moch, Holger; Beyer, Jörg; Hermanns, Thomas (2022). Impact of differing methodologies for serum miRNA-371a-3p assessment in stage I testicular germ cell cancer recurrence. Frontiers in Oncology, 12:1056823.

Wegener, Nadija; Balabanov, Stefan (2022). Klinische Zeichen eines myelodysplastischen Syndroms. Therapeutische Umschau. Revue thérapeutique, 78(2):71-75.

Schwab, Fabienne D; Scheidmann, Manuel C; Ozimski, Lauren L; Kling, André; Armbrecht, Lucas; Ryser, Till; Krol, Ilona; Strittmatter, Karin; Nguyen-Sträuli, Bich Doan; Jacob, Francis; Fedier, André; Heinzelmann-Schwarz, Viola; Wicki, Andreas; Dittrich, Petra S; Aceto, Nicola (2022). MyCTC chip: microfluidic-based drug screen with patient-derived tumour cells from liquid biopsies. Microsystems & Nanoengineering, 8:130.

Hofer, Kevin. Real-world outcomes in elderly ALL patients with and without allogeneic hematopoietic stem cell transplantation: a single-center evaluation over 10 years. 2022, University of Zurich, Medizinische Fakultät.

Schmid, Severin; Becker, Heiko; Fritsch, Ralph; Bausch, Johannes; Hunter, Natalie; Jenkner, Carolin; Hassan, Mohamed; Passlick, Bernward (2022). Study Protocol for a Randomised Controlled Trial on Pulmonary Metastasectomy vs. Standard of Care in Colorectal Cancer Patients With ≥ 3 Lung Metastases (PUCC-Trial). Frontiers in Oncology, 12:913896.

Akhoundova, Dilara; Haberecker, Martina; Fritsch, Ralph; Höller, Sylvia; Kiessling, Michael K; Rechsteiner, Markus; Rüschoff, Jan H; Curioni-Fontecedro, Alessandra (2022). Targeting ALK in Neuroendocrine Tumors of the Lung. Frontiers in Oncology, 12:911294.

Moretti, Alex; Ponzo, Marianna; Nicolette, Charles A; Tcherepanova, Irina Y; Biondi, Andrea; Magnani, Chiara F (2022). The Past, Present, and Future of Non-Viral CAR T Cells. Frontiers in Immunology, 13:867013.

2023

Menchinskaya, Ekaterina S; Dyshlovoy, Sergey A; Venz, Simone; Jacobsen, Christine; Hauschild, Jessica; Rohlfing, Tina; Silchenko, Aleksandra S; Avilov, Sergey A; Balabanov, Stefan; Bokemeyer, Carsten; Aminin, Dmitry L; von Amsberg, Gunhild; Honecker, Friedemann (2023).  Anticancer Activity of the Marine Triterpene Glycoside Cucumarioside A2-2 in Human Prostate Cancer Cells. Marine Drugs, 22(1):20.

Miller, Peter Grant; Sperling, Adam S; Mayerhofer, Christina; McConkey, Marie E;  Ellegast, Jana Maria; Da Silva, Carmen; Cohen, Drew Nathaniel; Wang, Chuqi; Sharda, Azeem; Yan, Ni; Saha, Subha; Schluter, Cameron; Schechter, Ilexa; Słabicki, Mikołaj; Sandoval, Brittany; Kahn, Josephine; Boettcher, Steffen; Gibson, Christopher J; Scadden, David T; Stegmaier, Kimberly; Bhatt, Shruti; Lindsley, R Coleman; Ebert, Benjamin L (2023).  PPM1D modulates hematopoietic cell fitness and response to DNA damage and is a therapeutic target in myeloid malignancy. Blood, 142(24):2079-2091.

Saito, Yasuyuki; Iida-Norita, Rie; Afroj, Tania; Refaat, Alaa; Hazama, Daisuke; Komori, Satomi; Ohata, Shinya; Takai, Tomoko; Oduori, Okechi S; Kotani, Takenori; Funakoshi, Yohei; Koma, Yu-Ichiro; Murata, Yoji; Yakushijin, Kimikazu; Matsuoka, Hiroshi; Minami, Hironobu; Yokozaki, Hiroshi;  Manz, Markus G; Matozaki, Takashi (2023). Preclinical evaluation of the efficacy of an antibody to human SIRPα for cancer immunotherapy in humanized mouse models. Frontiers in Immunology, 14:1294814.

Wilk, C Matthias; Cathomas, Flurin; Török, Orsolya; Le Berichel, Jessica; Park, Matthew D; Bigenwald, Camille; Heaton, George R; Hamon, Pauline; Troncoso, Leanna; Scull, Brooks P; Dangoor, Diana; Silvin, Aymeric; Fleischmann, Ryan; Belabed, Meriem; Lin, Howard; Merad Taouli, Elias;  Boettcher, Steffen; Li, Long; Aubry, Antonio;  Manz, Markus G;  Kofler, Julia K; Yue, Zhenyu; Lira, Sergio A; Ginhoux, Florent; Crary, John F; McClain, Kenneth L; Picarsic, Jennifer L; Russo, Scott J; Allen, Carl E; Merad, Miriam (2023). Circulating senescent myeloid cells infiltrate the brain and cause neurodegeneration in histiocytic disorders. Immunity, 56(12):27902802.e6.

Nadeu, Ferran; Syrykh, Charlotte; Pons-Brun, Berta; Russiñol, Núria; Playa-Albinyana, Heribert; Baumann, Tycho Stephan; Duran-Ferrer, Martí; Kulis, Marta; Carbó-Meix, Anna; Mozas, Pablo; Alcoceba, Miguel; González, Marcos; Navarro-Bailón, Almudena; Colado, Enrique; Payer, Ángel; Aymerich, Marta; Terol, María José; Lu, Junyan; Knisbacher, Binyamin Asher; Hahn, Cynthia K; Ruiz-Gaspà, Sílvia; Enjuanes, Anna; Wu, Catherine J; Getz, Gad;  Zenz, Thorsten; López-Guillermo, Armando; Martin-Subero, Jose I; Colomer, Dolors; Delgado, Julio; Campo, Elías (2023). IGLV321R110 mutation has prognostic value in patients with treatmentnaive chronic lymphocytic leukemia. Blood Advances, 7(23):73847391.

Volta, Laura;  Manz, Markus G (2023).  Twisted: Escape of epitope-edited healthy cells from immune attack. Journal of Experimental Medicine, 220(12):e20231635.

von der Grün, Jens; Ahmadsei, Maiwand; Breyer, Isabel; Britschgi, Christian; Eberli, Daniel; Hermanns, Thomas; Mangana, Joanna; Petrowsky, Henrik; Ramelyte, Egle; Roth, Patrick; Schär, Gabriel; Opitz, Isabelle; Weller, Michael;  Wicki, Andreas; Witzel, Isabell; Balermpas, Panagiotis; Guckenberger, Matthias (2023).  Patient recruitment into clinical studies of solid malignancies during the COVID-19 pandemic in a tertiary cancer center. Neoplasia, 46:100946.

Tettero, Jesse M; Buisman, Yara; Ngai, Lok Lam; Bachas, Costa; Gjertsen, Bjorn T; Kelder, Angèle; van de Loosdrecht, Arjan A;  Manz, Markus G; Pabst, Thomas; Scholten, Willemijn; Ossenkoppele, Gert J; Cloos, Jacqueline; de Leeuw, David C (2023). Prognostic Significance of Measurable Residual Disease Detection by Flow Cytometry in Autologous Stem Cell Apheresis Products in AML. HemaSphere, 7(12):e981.

Chamuleau, Martine E D; Stenner, Frank; Chitu, Dana A; Novak, Urban; Minnema, Monique C; Geerts, Paul; Stevens, Wendy B C; Zenz, Thorsten; van Imhoff, Gustaaf W; Wu, Ka Lung; Demandt, Astrid M P; Kersten, Marie Jose; Terpstra, Wim E; Tick, Lidwine W; Deeren, Dries; Van Den Neste, Eric; Gregor, Michael; Veelken, Hendrik; Böhmer, Lara H; Caspar, Clemens B; Mutsaers, Pim; Refos, Jeannine M; Sewsaran, Robby; Fu, Liping; Seefat, Rianne L; Uyl-de Groot, Carin A; Dirnhofer, Stefan; Van Den Brand, Michiel; de Jong, Daphne; Nijland, Marcel; et al (2023). R-CODOXM/R-IVAC versus DA-EPOCH-R in patients with newly diagnosed Burkitt lymphoma (HOVON/SAKK): final results of a multicentre, phase 3, open-label, randomised trial. The Lancet Haematology, 10(12):e966-e975.

Nishida, Yuki; Ishizawa, Jo; Ayoub, Edward; Montoya, Rafael Heinz; Ostermann, Lauren B; Muftuoglu, Muharrem; Ruvolo, Vivian R; Patsilevas, Tallie; Scruggs, Darah A; Khazaei, Shayaun; Mak, Po Yee; Tao, Wenjing; Carter, Bing Z; Boettcher, Steffen; Ebert, Benjamin L; Daver, Naval G; Konopleva, Marina; Seki, Takahiko; Kojima, Kensuke; Andreeff, Michael (2023).  Enhanced TP53 reactivation disrupts MYC transcriptional program and overcomes venetoclax resistance in acute myeloid leukemias. Science Advances, 9(48):eadh1436.

Djerbi, Nadia; Zimmermann, Kathrin;  Roncador, Marco; Becker, Mike Oliver;  Manz, Markus G; Balabanov, Stefan (2023).  Intrapatient competition of VEXAS syndrome and CML clones. Blood Advances, 7(22):6815-6818.

Glüge, Stefan;  Balabanov, Stefan; Koelzer, Viktor Hendrik; Ott, Thomas (2023).  Evaluation of deep learning training strategies for the classification of bone marrow cell images. Computer Methods and Programs in Biomedicine, 243:107924.

Grünwald, Viktor; Ivanyi, Philipp; Zschäbitz, Stefanie; Wirth, Manfred; Staib, Peter; Schostak, Martin; Dargatz, Philip; Müller, Lothar; Metz, Michael; Bergmann, Lothar; Steiner, Thomas; Welslau, Martin;  Lorch, Anja; Rafiyan, Reza; Hellmis, Eva; Darr, Cristopher; Schütt, Philipp; Meiler, Johannes; Kretz, Thomas; Loidl, Wolfgang; Flörcken, Anne; Mänz, Martin; Hinke, Axel; Hartmann, Arndt; Grüllich, Carsten (2023).  Nivolumab Switch Maintenance Therapy After Tyrosine Kinase Inhibitor Induction in Metastatic Renal Cell Carcinoma: A Randomized Clinical Trial by the Interdisciplinary Working Group on Renal Tumors of the German Cancer Society (NIVOSWITCH; AIO-NZK-0116ass). European Urology, 84(6):571-578.

Pavic, Matea; Wolfer, Anita; Li, Qiyu; Gircys, Arunas; Juritz, Stephanie;  Wicki, Andreas; Cerny, Thomas; Rohr, Ulrich-Peter (2023).  Regulatory Challenges: Is a Surrogate End Point Instead of Overall Survival Enough for Regulatory Approval of (Neo)Adjuvant Cancer Treatment? The Swissmedic Perspective. Journal of Clinical Oncology, 41(32):4973-4975.

Hänsch, Lena; Peipp, Matthias; Mastall, Maximilian; Villars, Danielle;  Myburgh, Renier; Silginer, Manuela;  Weiss, Tobias; Gramatzki, Dorothee; Vasella, Flavio; Manz, Markus G; Weller, Michael; Roth, Patrick (2023).  Chimeric antigen receptor T cellbased targeting of CD317 as a novel immunotherapeutic strategy against glioblastoma. Neuro-Oncology, 25(11):2001-2014.

Pabst, Thomas; Papayannidis, Cristina; Demirkan, Fatih; Doronin, Vadim; Fogliatto, Laura M; Guttke, Christina; Gyan, Emmanuel; Hamad, Nada; Herrera, Pilar; Hultberg, Anna; Jacobs, Julie; Johnson,

Amy J; Langlois, Angélique; Ma, Xuewen;  Martinelli, Giovanni; Arnan, Montserrat;  Müller, Rouven; Nottage, Kerri; Ofran, Yishai;  Özcan, Muhit; Samoilova, Olga; Tolbert, Jaszianne A; Trudel, Géralyn C; Xiu, Liang; Vey, Norbert; Wei, Andrew H (2023).  Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study. The Lancet Haematology, 10(11):e902-e912.

Rha, Sun Young; Oh, Do-Youn; Yañez, Patricio; Bai, Yuxian; Ryu, Min-Hee; Lee, Jeeyun; Rivera, Fernando; Alves, Gustavo Vasconcelos; Garrido, Marcelo; Shiu, Kai-Keen; Fernández, Manuel González; Li, Jin; Lowery, Maeve A;  Çil, Timuçin; Cruz, Felipe Melo; Qin, Shukui; Luo, Suxia; Pan, Hongming; Wainberg, Zev A; Yin, Lina; Bordia, Sonal; Bhagia, Pooja; Wyrwicz, Lucjan S; KEYNOTE-859 investigators; Fritsch, Ralph (2023). Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncology, 24(11):1181-1195.

Ecker, Veronika; Brandmeier, Lisa; Stumpf, Martina; Giansanti, Piero; Moreira, Aida Varela; Pfeuffer, Lisa; Fens, Marcel H A M; Lu, Junyan; Kuster, Bernhard; Engleitner, Thomas; Heidegger, Simon; Rad, Roland; Ringshausen, Ingo;  Zenz, Thorsten;  Wendtner, Clemens-Martin; Müschen, Markus; Jellusova, Julia; Ruland, Jürgen; Buchner, Maike (2023).  Negative feedback regulation of MAPK signaling is an important driver of chronic lymphocytic leukemia progression. Cell Reports, 42(10):113017.

Sarvan, Milos; Etienne, Harry;  Bankel, Lorenz; Brown, Michelle L; Schneiter, Didier; Opitz, Isabelle (2023).  Outcome Analysis of Treatment Modalities for Thoracic Sarcomas. Cancers, 15(21):5154. Germans, Menno R; Rohr, Jonas; Globas, Christoph; Schubert, Tilman; Kaserer, Alexander; Brandi, Giovanna;  Studt, JanDirk; Greutmann, Matthias; Geiling, Katharina; Verweij, Lotte; Regli, Luca (2023).  Challenges in Coagulation Management in Neurosurgical Diseases: A Scoping Review, Development, and Implementation of Coagulation Management Strategies. Journal of Clinical Medicine, 12(20):6637.

Wildschut, Mattheus H E; Mena, Julien; Dördelmann, Cyril; van Oostrum, Marc; Hale, Benjamin D; Settelmeier, Jens; Festl, Yasmin;  Lysenko, Veronika; Schürch, Patrick M; Ring, Alexander; Severin, Yannik; Bader, Michael S; Pedrioli, Patrick G A; Goetze, Sandra; van Drogen, Audrey;  Balabanov, Stefan; Skoda, Radek C; Lopes, Massimo; Wollscheid, Bernd;  Theocharides, Alexandre P A ; Snijder, Berend (2023).  Proteogenetic drug response profiling elucidates targetable vulnerabilities of myelofibrosis. Nature Communications, 14(1):6414.

Wilk, C Matthias; Cathomas, Flurin; Török, Orsolya; Le Berichel, Jessica; Park, Matthew D; Heaton, George R; Hamon, Pauline; Troncoso, Leanna; Scull, Brooks P; Dangoor, Diana; Silvin, Aymeric; Fleischmann, Ryan; Belabed, Meriem; Lin, Howard; Taouli, Elias Merad; Boettcher, Steffen; Manz, Markus G; Kofler, Julia K; Yue, Zhenyu; Lira, Sergio A; Ginhoux, Florent; Crary, John F; McClain, Kenneth L; Picarsic, Jennifer L; Russo, Scott J; Allen, Carl E; Merad, Miriam (2023). Circulating senescent myeloid cells drive blood brain barrier breakdown and neurodegeneration. bioRxiv 561744, University of Zurich.

Herbst, Sophie A; Kim, Vladislav; Roider, Tobias; Schitter, Eva C; Bruch, Peter-Martin; Liebers, Nora; Kolb, Carolin; Knoll, Mareike; Lu, Junyan; Dreger, Peter; Müller-Tidow, Carsten;  Zenz, Thorsten; Huber, Wolfgang; Dietrich, Sascha (2023).  Comparing the value of mono- vs coculture for high-throughput compound screening in hematological malignancies. Blood Advances, 7(19):5925-5936.

Liebers, Nora; Bruch, Peter-Martin; Terzer, Tobias; Hernandez-Hernandez, Miguel; Paramasivam, Nagarajan; Fitzgerald, Donnacha; Altmann, Heidi; Roider, Tobias; Kolb, Carolin; Knoll, Mareike;  Lenze, Angela; Platzbecker, Uwe; Röllig, Christoph; Baldus, Claudia; Serve, Hubert; Bornhäuser, Martin; Hübschmann, Daniel; Müller-Tidow, Carsten; Stölzel, Friedrich; Huber, Wolfgang; Benner, Axel; Zenz, Thorsten; Lu, Junyan; Dietrich, Sascha (2023). Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial. Nature Cancer, 4(12):1648-1659.

Buljan, Marija; Banaei-Esfahani, Amir; Blattmann, Peter;  MeierAbt, Fabienne; Shao, Wenguang; Vitek, Olga; Tang, Hua; Aebersold, Ruedi (2023).  A computational framework for the inference of protein complex remodeling from whole-proteome measurements. Nature Methods, 20(10):1523-1529.

Rieger, Max J; Schenkel, Xenia; Dedic, Ivona; Brunn, Tadeusz; Gnannt, Ralph; Hofmann, Michael; de Rougemont, Olivier; Stolz, Sebastian M; Rösler, Wiebke; Studt, Jan-Dirk; Balabanov, Stefan; Wicki, Andreas; Lorch, Anja; Manz, Markus G; Schwotzer, Rahel (2023).  Complication rates of peripherally inserted central catheters vs implanted ports in patients receiving systemic anticancer therapy: A retrospective cohort study. International Journal of Cancer, 153(7):1397-1405.

Tettero, Jesse M; Ngai, Lok Lam; Bachas, Costa; Breems, Dimitri A; Fischer, Thomas; Gjertsen, Bjorn T; Gradowska, Patrycja; Griskevicius, Laimonas; Janssen, Jeroen J W M; Juliusson, Gunnar; Maertens, Johan; Manz, Markus G; Pabst, Thomas; Passweg, Jakob; Porkka, Kimmo; Valk, Peter J M; Löwenberg, Bob; Ossenkoppele, Gert J; Cloos, Jacqueline (2023). Measurable residual disease-guided therapy in intermediate-risk acute myeloid leukemia patients is a valuable strategy in reducing allogeneic transplantation without negatively affecting survival. Haematologica, 108(10):2794-2798.

Lütge, Almut; Lu, Junyan; Hüllein, Jennifer; Walther, Tatjana; Sellner, Leopold; Wu, Bian; Rosenquist, Richard; Oakes, Christopher C; Dietrich, Sascha; Huber, Wolfgang; Zenz, Thorsten (2023). Subgroup-specific gene expression profiles and mixed epistasis in chronic lymphocytic leukemia. Haematologica, 108(10):26642676.

Marques-Maggio, Ewerton; Maccio, Umberto; Marx, Alexandra; Galli, Serena; Schwab, Nathalie; Frank, Angela; Hamelin, Baptiste; Varga, Zsuzsanna;  Nombela-Arrieta, César; Mertz, Kirsten D; Theocharides, Alexandre Pa; Koelzer, Viktor H (2023). Bone marrow haematopoiesis in patients with COVID-19. Histopathology, 83(4):582-590.

Stricker, Helena Marie; Wicki, Andreas (2023).  Langzeitnebenwirkungen der Immuncheckpoint-Inhibitoren. Therapeutische Umschau : Monatsschrift für praktische Medizin, 80(8):367-372.

Fischer, Jacqueline; Erkner, Estelle; Fitzel, Rahel; Radszuweit, Pia; Keppeler, Hildegard; Korkmaz, Fulya; Roti, Giovanni; Lengerke, Claudia;  Schneidawind, Dominik; Schneidawind, Corina (2023).  Uncovering NOTCH1 as a Promising Target in the Treatment of MLL-Rearranged Leukemia. International Journal of Molecular Sciences, 24(19):14466.

Magnani, Chiara F; Myburgh, Renier;  Brunn, Silvan; Chambovey, Morgane; Ponzo, Marianna; Volta, Laura; Manfredi, Francesco; Pellegrino, Christian; Pascolo, Steve; Miskey, Csaba; Ivics, Zoltán; Shizuru, Judith A; Neri, Dario;  Manz, Markus G (2023).  Anti-CD117 CAR T cells incorporating a safety switch eradicate human acute myeloid leukemia and hematopoietic stem cells. Molecular Therapy : Oncolytics, 30:56-71.

Carter, Bing Z; Mak, Po Yee; Muftuoglu, Muharrem; Tao, Wenjing; Ke, Baozhen; Pei, Jingqi; Bedoy, Andrea D; Ostermann, Lauren B; Nishida, Yuki; Isgandarova, Sevinj; Sobieski, Mary; Nguyen, Nghi; Powell, Reid T; Martinez-Moczygemba, Margarita; Stephan, Clifford; Basyal, Mahesh; Pemmaraju, Naveen;  Boettcher, Steffen; Ebert, Benjamin L; Shpall, Elizabeth J; Wallner, Barbara; Morgan, Robert A; Karras, Georgios I; Moll, Ute M; Andreeff, Michael (2023).  Epichaperome inhibition targets TP53-mutant AML and AML stem/progenitor cells. Blood, 142(12):1056-1070.

Maru, Bruktawit; Messikommer, Alessandra; Huang, Linhui; Seipel, Katja; Kovecses, Olivia; Valk, Peter J M;  Theocharides, Alexandre P A ; Mercier, Francois E; Pabst, Thomas; McKeague, Maureen; Luedtke, Nathan W (2023).  PARP-1 improves leukemia outcomes by inducing parthanatos during chemotherapy. Cell Reports Medicine, 4(9):101191.

Speicher, Philip; Fankhauser, Christian D;  Lorch, Anja;  Ardizzone, Davide; Helnwein, Simon; Hoch, Dennis; Hermanns, Thomas; Beyer, Jörg; Akhoundova, Dilara (2023).  Excellent survival in relapsed stage I testicular cancer. BMC Cancer, 23(1):870.

Bonini, Chiara; Chapuis, Aude G; Hudecek, Michael; Guedan, Sonia;  Magnani, Chiara; Qasim, Waseem (2023).  Genome Editing in Engineered T Cells for Cancer Immunotherapy. Human Gene Therapy, 34(17-18):853-869.

Rejeski, Kai; Subklewe, Marion; Aljurf, Mahmoud; Bachy, Emmanuel; Balduzzi, Adriana; Barba, Pere; Bruno, Benedetto; Benjamin, Reuben; Carrabba, Matteo G; Chabannon, Christian; Ciceri, Fabio; Corradini, Paolo; Delgado, Julio; Di Blasi, Roberta; Greco, Raffaella; Houot, Roch; Iacoboni, Gloria; Jäger, Ulrich; Kersten, Marie José; Mielke, Stephan; Nagler, Arnon; Onida, Francesco; Peric, Zinaida; Roddie, Claire; Ruggeri, Annalisa; Sánchez-Guijo, Fermín; Sánchez-Ortega, Isabel;  Schneidawind, Dominik; Schubert, Maria-Luisa; Snowden, John A; et al (2023).  Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations. Blood, 142(10):865-877.

Cefalì, Marco; Scala, Isabel; Pavone, Giuliana; Helbling, Daniel;  Hussung, Saskia; Fritsch, Ralph; Reiner, Cäcilia; Stocker, Soleen; Koeberle, Dieter; Kissling, Marc; Chianca, Vito; Del Grande, Filippo; De Dosso, Sara; Rizzo, Stefania (2023). Is Computed-Tomography-Based Body Composition a Reliable Predictor of Chemotherapy-Related Toxicity in Pancreatic Cancer Patients? Cancers, 15(17):4398.

Lauinger, Manuel; Christen, Daniel; Klar, Rhena F U; Roubaty, Carole; Heilig, Christoph E; Stumpe, Michael; Knox, Jennifer J; Radulovich, Nikolina; Tamblyn, Laura; Xie, Irene Y; Horak, Peter; Forschner, Andrea; Bitzer, Michael; Wittel, Uwe A; Boerries, Melanie; Ball, Claudia R; Heining, Christoph; Glimm, Hanno; Fröhlich, Martina; Hübschmann, Daniel; Gallinger, Steven;  Fritsch, Ralph; Fröhling, Stefan; O’Kane, Grainne M; Dengjel, Jörn; Brummer, Tilman (2023).  BRAFΔβ 3− α C in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability. Science Advances, 9(35):eade7486.

Fritsch, Ralph; Hempel, Chiara Louisa (2023).  Intensification and Personalization of Neoadjuvant Therapy for Locally Advanced Rectal Cancer. Praxis, 112(11):537.

Hammerer-Lercher, Angelika; Nilius, Henning; Studt, Jan-Dirk; Tsakiris, Dimitrios A; Greinacher, Andreas; Mendez, Adriana; Schmidt, Adrian; Wuillemin, Walter A;  Gerber, Bernhard;  Kremer Hovinga, Johanna A; Vishnu, Prakash; Graf, Lukas; Bakchoul, Tamam; Nagler, Michael (2023).  Limited concordance of heparin/platelet factor 4 antibody assays for the diagnosis of heparin-induced thrombocytopenia: an analysis of the TORADI-HIT study. Journal of Thrombosis and Haemostasis, 21(9):2559-2568.

Templeton, Arnoud J; Omlin, Aurelius; Berthold, Dominik;  Beyer, Jörg;  Burger, Irene A; Eberli, Daniel; Engeler, Daniel; Fankhauser, Christian; Fischer, Stefanie; Gillessen, Silke; Nicolas, Guillaume; Kroeze, Stephanie; Lorch, Anja; Müntener, Michael; Papachristofilou, Alexandros; Schaefer, Niklaus; Seiler, Daniel; Stenner, Frank; Tsantoulis, Petros; Vlajnic, Tatjana; Zilli, Thomas; Zwahlen, Daniel; Cathomas, Richard (2023).  Interdisciplinary Swiss consensus recommendations on staging and treatment of advanced prostate cancer. Swiss Medical Weekly, 153(8):40108.

von Stauffenberg, Franz; Hegemann, Inga; Schwotzer, Rahel; Lehmann, Kuno; Widmer, Jeannette (2023). Management of abdominal pseudotumours in haemophilia: a systematic review. Swiss Medical Weekly, 153(8):40094.

Hoch, Dennis; Helnwein, Simon; Adrizzone, Davide;  Lorch, Anja; Fankhauser, Christian; Hermanns, Thomas; Thalmann, George; Beyer, Jörg (2023). No Survival Differences among GermCell Cancer Patients from Urban and Rural Areas. Oncology Research and Treatment, 46(10):433-437. Carbo-Meix, Anna; Guijarro, Francesca; Wang, Luojun; Grau, Marta; Royo, Romina; Frigola, Gerard; Playa-Albinyana, Heribert; Bühler, Marco M; Clot, Guillem; Duran-Ferrer, Marti; Lu, Junyan; Granada, Isabel; Baptista, Maria-Joao; Navarro, Jose-Tomas; Espinet, Blanca; Puiggros, Anna; Tapia, Gustavo; Bandiera, Laura; De Canal, Gabriella; Bonoldi, Emanuela; Climent, Fina; Ribera-Cortada, Inmaculada; Fernandez-Caballero, Mariana; De la Banda, Esmeralda; Do Nascimento, Janilson; Pineda, Alberto; Vela, Dolors; Rozman, Maria; Aymerich, Marta; Syrykh, Charlotte;  Zenz, Thorsten; et al (2023).  BCL3-rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases. Haematologica, 109(2):493-508. Grockowiak, Elodie; Korn, Claudia; Rak, Justyna; Lysenko, Veronika; Hallou, Adrien; Panvini, Francesca M; Williams, Matthew; Fielding, Claire; Fang, Zijian; Khatib-Massalha, Eman; García-García, Andrés; Li, Juan; Khorshed, Reema A; González-Antón, Sara; Baxter, E Joanna; Kusumbe, Anjali; Wilkins, Bridget S; Green, Anna; Simons, Benjamin D; Harrison, Claire N; Green, Anthony R; Lo Celso, Cristina;  Theocharides, Alexandre P A ; Méndez-Ferrer, Simón (2023). Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms. Nature Cancer, 4(8):1193-1209.

Ni, Ruiqing; Straumann, Nadja;  Fazio, Serana; Dean-Ben, Xose Luis; Louloudis, Georgios; Keller, Claudia; Razansky, Daniel; Ametamey, Simon; Mu, Linjing;  Nombela-Arrieta, César; Klohs, Jan (2023).  Imaging increased metabolism in the spinal cord in mice after middle cerebral artery occlusion. Photoacoustics, 32:100532.

Angelillo-Scherrer, Anne; Casini, Alessandro; Studt, Jan-Dirk; Gerber, Bernhard; Alberio, Lorenzo A; Fontana, Pierre (2023). Recommendations for the use of andexanet alfa in the management of bleeding in patients on oral factor Xa inhibitors in Switzerland: Guideline from the Working Party Hemostasis of the Swiss Society of Hematology. Swiss Medical Weekly, 153:40113.

Rieger, Max J; Stolz, Sebastian M; Müller, Antonia M;  Schwotzer, Rahel; Nair, Gayathri; Schneidawind, Dominik; Manz, Markus G; Schanz, Urs (2023).  Haploidentical transplant with posttransplant cyclophosphamide vs matched related and unrelated donor transplant in acute myeloid leukemia and myelodysplastic neoplasm. Bone Marrow Transplantation, 58(10):1121-1129.

Hiester, Andreas; Che, Yue; Lusch, Achim; Kuß, Oliver; Niegisch, Günter;  Lorch, Anja;  Arsov, Christian; Albers, Peter (2023).  Phase 2 Single-arm Trial of Primary Retroperitoneal Lymph Node Dissection in Patients with Seminomatous Testicular Germ Cell Tumors with Clinical Stage IIA/B (PRIMETEST). European Urology, 84(1):25-31.

Pabst, Thomas; Vey, Norbert; Adès, Lionel; Bacher, Ulrike; Bargetzi, Mario; Fung, Samson; Gaidano, Gianluca; Gandini, Domenica; Hultberg, Anna; Johnson, Amy; Ma, Xuewen;  Müller, Rouven; Nottage, Kerri; Papayannidis, Cristina; Recher, Christian; Riether, Carsten; Shah, Priya; Tryon, Jeffrey; Xiu, Liang; Ochsenbein, Adrian F (2023).  Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy. Haematologica, 108(7):1793-1802.

Fitzel, Rahel; Secker-Grob, Kathy-Ann; Keppeler, Hildegard; Korkmaz, Fulya; Schairer, Rebekka; Erkner, Estelle;  Schneidawind, Dominik; Lengerke, Claudia; Hentrich, Thomas; Schulze-Hentrich, Julia M; Schneidawind, Corina (2023). Targeting MYC in combination with epigenetic regulators induces synergistic anti-leukemic effects in MLLr leukemia and simultaneously improves immunity. Neoplasia, 41:100902.

Marion, William; Koppe, Tiago; Chen, Chun-Chin; Wang, Dahai; Frenis, Katie; Fierstein, Sara; Sensharma, Prerana; Aumais, Olivia; Peters, Michael; Ruiz-Torres, Sonya; Chihanga, Tafadzwa;  Boettcher, Steffen; Shimamura, Akiko; Bauer, Daniel E; Schlaeger, Thorsten; Wells, Susanne I; Ebert, Benjamin L; Starczynowski, Daniel; da Rocha, Edroaldo Lummertz; Rowe, R Grant (2023).  RUNX1 mutations mitigate quiescence to promote transformation of hematopoietic progenitors in Fanconi anemia. Leukemia, 37(8):1698-1708.

Burger, Annika; Studt, Jan-Dirk; Mendez, Adriana; Alberio, Lorenzo; Fontana, Pierre; Wuillemin, Walter A; Schmidt, Adrian; Graf, Lukas;  Gerber, Bernhard; Bovet, Cédric; Sauter, Thomas C; Binder, Nikolaus B; Nagler, Michael (2023).  Determination of Anti-Xa Inhibitor Plasma Concentrations Using a Universal Edoxaban Calibrator. Diagnostics, 13(12):2128.

Hilberink, Jacobien R; van Zeventer, Isabelle A; Chitu, Dana A; Pabst, Thomas; Klein, Saskia K; Stussi, Georg; Griskevicius, Laimonas; Valk, Peter J M; Cloos, Jacqueline; van de Loosdrecht, Arjan A; Breems, Dimitri; van Lammeren-Venema, Danielle; Boersma, Rinske; Jongen-Lavrencic, Mojca; Fehr, Martin; Hoogendoorn, Mels;  Manz, Markus G; Söhne, Maaike; van Marwijk Kooy, Rien; Deeren, Dries; van der Poel, Marjolein W M; Legdeur, Marie Cecile; Tick, Lidwine; Chalandon, Yves; Ammatuna, Emanuele; Blum, Sabine; Löwenberg, Bob; Ossenkoppele, Gert J; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); Swiss Group for Clinical Cancer Research (SAKK); et al (2023).  Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine. Blood Cancer Journal, 13(1):93.

Elsayed, Abdullah; Pellegrino, Christian; Plüss, Louis; Peissert, Frederik; Benz, Ramon; Ulrich, Franziska; Thorhallsdottir, Gudrun; Plaza, Sheila Dakhel; Villa, Alessandra; Mock, Jacqueline; Puca, Emanuele; De Luca, Roberto; Manz, Markus G; Halin, Cornelia; Neri, Dario (2023).  Generation of a novel fully human non-superagonistic anti-CD28 antibody with efficient and safe T-cell co-stimulation properties. mAbs, 15(1):2220839.

Yan, Yuqian; López-Alcalde, Jesús; Zhang, Linxin;  Siebenhüner, Alexander R; Witt, Claudia M; Barth, Jürgen (2023).  Acupuncture for the prevention of chemotherapy-induced nausea and vomiting in cancer patients: A systematic review and meta-analysis. Cancer Medicine, 12(11):12504-12517.

Lysenko, Veronika;  Schürch, Patrick M; Tuzlak, Selma; van Wijk, Nicole Wildner-Verhey ;  Kovtonyuk, Larisa V; Becher, Burkhard;  Manz, Markus G; Kreutmair, Stefanie; Theocharides, Alexandre P A (2023).  Blocking the CD47-SIRPα interaction reverses the disease phenotype in a polycythemia vera mouse model. Leukemia, 37(6):1277-1286.

Mehra, Tarun; Dongre, Kanchan; Boesing, Maria; Frei, Patricia; Suenderhauf, Claudia; Zippelius, Alfred; Leuppi, Joerg D;  Wicki, Andreas; Leuppi-Taegtmeyer, Anne B (2023).  Pre-treatment comorbidities, C-reactive protein and eosinophil count, and immune-related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities. Cancer Medicine, 12(11):12253-12262.

Ngai, Lok Lam; Hanekamp, Diana; Janssen, Fleur; Carbaat-Ham, Jannemieke; Hofland, Maaike A M A; Fayed, Mona M H E; Kelder, Angèle; Oudshoorn-van Marsbergen, Laura; Scholten, Willemijn J; Snel, Alexander N; Bachas, Costa; Tettero, Jesse M; Breems, Dimitri A; Fischer, Thomas; Gjertsen, Bjørn T; Griškevičius, Laimonas; Juliusson, Gunnar; van de Loosdrecht, Arjan A; Maertens, Johan A; Manz, Markus G; Pabst, Thomas; Passweg, Jakob R; Porkka, Kimmo; Valk, Peter J M; Gradowska, Patrycja; Löwenberg, Bob; de Leeuw, David C; Janssen, Jeroen J W M; Ossenkoppele, Gert J; Cloos, Jacqueline (2023).  Prospective validation of the prognostic relevance of CD34+CD38− AML stem cell frequency in the HOVON-SAKK132 trial. Blood, 141(21):2657-2661. Shao, Lijian; Paik, Na Yoon; Sanborn, Mark A; Bandara, Thilinie; Vijaykumar, Anjali; Sottoriva, Kilian; Rehman, Jalees;  Nombela-Arrieta, César; Pajcini, Kostandin V (2023).  Hematopoietic Jagged1 is a fetal liver niche factor required for functional maturation and engraftment of fetal hematopoietic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 120(20):e2210058120.

Omlin, Aurelius; Cathomas, Richard; von Amsberg, Gunhild; Reuter, Christoph; Feyerabend, Susan; Loidl, Wolfgang; Boegemann, Martin;  Lorch, Anja;  Heidenreich, Axel; Tsaur, Igor; Larcher-Senn, Julian; Buck, Stefan A J; Mathijssen, Ron H J; Jaehde, Ulrich; Gillessen, Silke; Joerger, Markus (2023). Randomized Phase II Cabazitaxel Dose Individualization and Neutropenia Prevention Trial in Patients with Metastatic Castration-Resistant Prostate Cancer. Clinical Cancer Research, 29(10):1887-1893.

Barz, Malwine Jeanette; Behrmann, Lena; Capron, Danaëlle; Zuchtriegel, Gabriele; Steffen, Fabio D; Kunz, Leo; Zhang, Yang; Vermeerbergen, Iria Jimenez; Marovca, Blerim; Kirschmann, Moritz; Zech, Antonia;  Nombela-Arrieta, Cesar; Ziegler, Urs; Schroeder, Timm; Bornhauser, Beat; Bourquin, Jean-Pierre (2023). B and T cell acute lymphoblastic leukemia evade chemotherapy at distinct sites in the bone marrow. Haematologica, 108(5):1244-1258.

Neuenschwander, Anne; Lonati, Chiara; Antonelli, Luca; Papachristofilou, Alexandros; Cathomas, Richard; Rothermundt, Christian; Templeton, Arnoud J; Gulamhusein, Aziz; Fischer, Stefanie; Gillessen, Silke; Hermanns, Thomas;  Lorch, Anja; Mattei, Agostino; Fankhauser, Christian D (2023).  Treatment Outcomes for Men with Clinical Stage II Nonseminomatous Germ Cell Tumours Treated with Primary Retroperitoneal Lymph Node Dissection: A Systematic Review. European Urology Focus, 9(3):541-546.

Kropivsek, Klara; Kachel, Paul; Goetze, Sandra; Wegmann, Rebekka; Festl, Yasmin; Severin, Yannik; Hale, Benjamin D; Mena, Julien; van Drogen, Audrey; Dietliker, Nadja; Tchinda, Joëlle; Wollscheid, Bernd;  Manz, Markus G; Snijder, Berend (2023).  Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma. Nature Cancer, 4(5):734-753.

Menges, Dominik; Piatti, Michela C; Omlin, Aurelius; Cathomas, Richard; Benamran, Daniel; Fischer, Stefanie; Iselin, Christophe; Küng, Marc;  Lorch, Anja; Prause, Lukas; Rothermundt, Christian; O’Meara Stern, Alix; Zihler, Deborah; Lippuner, Max; Braun, Julia; Cerny, Thomas; Puhan, Milo A (2023).  Patient and General Population Preferences Regarding the Benefits and Harms of Treatment for Metastatic Prostate Cancer: A Discrete Choice Experiment. European Urology Open Science, 51:26-38.

van den Berg, Jana; Haslbauer, Jasmin D; Stalder, Anna K; Romanens, Anna; Mertz, Kirsten D; Studt, Jan-Dirk; Siegemund, Martin; Buser, Andreas; Holbro, Andreas; Tzankov, Alexandar (2023). Von Willebrand factor and the thrombophilia of severe COVID-19: in situ evidence from autopsies. Research and Practice in Thrombosis and Haemostasis, 7(4):100182.

Carter, Bing Z; Mak, Po Yee; Tao, Wenjing; Ayoub, Edward; Ostermann, Lauren B; Huang, Xuelin; Loghavi, Sanam; Boettcher, Steffen; Nishida, Yuki; Ruvolo, Vivian; Hughes, Paul E; Morrow, Phuong K; Haferlach, Torsten; Kornblau, Steven; Muftuoglu, Muharrem; Andreeff, Michael (2023).  Combined inhibition of BCL-2 and MCL-1 overcomes BAX deficiency-mediated resistance of TP53-mutant acute myeloid leukemia to individual BH3 mimetics. Blood Cancer Journal, 13(1):57.

Ring, Alexander; Sieber, Wolfgang Alexander; Studt, JanDirk; Schuepbach, Reto A; Ganter, Christoph Camille; Manz, Markus Gabriel; Müller, Antonia Maria Susanne; David, Sascha (2023).  Indications and Outcomes of Patients Receiving Therapeutic Plasma Exchange under Critical Care Conditions: A Retrospective Eleven-Year Single-Center Study at a Tertiary Care Center. Journal of Clinical Medicine, 12(8):2876.

Fiskus, Warren; Mill, Christopher P; Birdwell, Christine; Davis, John A; Das, Kaberi;  Boettcher, Steffen; Kadia, Tapan M; DiNardo, Courtney D; Takahashi, Koichi; Loghavi, Sanam; Soth, Michael J; Heffernan, Tim; McGeehan, Gerard M; Ruan, Xinjia; Su, Xiaoping; Vakoc, Christopher R; Daver, Naval; Bhalla, Kapil N (2023).  Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1. Blood Cancer Journal, 13(1):53.

Notarfrancesco, Marco; Fankhauser, Christian D;  Lorch, Anja; Ardizzone, Davide; Helnwein, Simon; Hoch, Dennis; Hermanns, Thomas; Thalmann, George; Beyer, Jörg (2023).  Perioperative complications and oncological outcomes of post-chemotherapy retroperitoneal lymph node dissection in patients with germ cell cancer at two high-volume university centres in Switzerland - a retrospective chart review. Swiss Medical Weekly, 153:40053.

Bankova, Andriyana K; Pasin, Chloé; Huang, Alice; Cicin-Sain, Caroline; Epp, Selina; Audigé, Annette; Mueller, Nicolas J; Nilsson, Jakob;  Vilinovszki, Oliver; Nair, Gayathri; Wolfensberger, Nathan; Hockl, Philipp; Schanz, Urs; Trkola, Alexandra; Kouyos, Roger; Hasse, Barbara; Zinkernagel, Annelies S;  Manz, Markus G;  Abela, Irene A;  Müller, Antonia M S (2023).  Antibody response to a third SARS-CoV-2 vaccine dose in recipients of an allogeneic haematopoietic cell transplantation. British Journal of Haematology, 201(1):58-63.

Gagesch, Michael;  Rösler, Wiebke; Bauernschmitt, Robert; Wilhelm, Markus J; Freystätter, Gregor (2023). Nutzen altersmedizinischer Abklärungen vor Operationen, Interventionen und onkologischen Therapien. Praxis, 112(5-6):340-347.

Laptseva, Natallia; Rossi, Valentina A; Sudano, Isabella; Schwotzer, Rahel; Ruschitzka, Frank; Flammer, Andreas J; Duru, Firat (2023). Arrhythmic Manifestations of Cardiac Amyloidosis: Challenges in Risk Stratification and Clinical Management. Journal of Clinical Medicine, 12(7):2581.

Bajka, Anahita; Muth, Daniel Rudolf; Wiest, Maximilian Robert Justus; Said, Sadiq; Rejdak, Magdalena; Sidhu, Sophia; Foa, Nastasia; Blaser, Frank; Barthelmes, Daniel; Toro, Mario Damiano; Souied, Eric H;  Deuel, Jeremy Werner; Schlagenhauf, Patricia; Zweifel, Sandrine Anne (2023).  Analysis of Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) Parameters in Young Adults after SARSCoV-2 Infection (COVID-19) Compared with Healthy Young Controls. Diagnostics, 13(7):1283.

Rösler, Wiebke; Altenbuchinger, Michael; Baeßler, Bettina; Beissbarth, Tim; Beutel, Gernot; Bock, Robert; von Bubnoff, Nikolas; Eckardt, Jan-Niklas; Foersch, Sebastian; Loeffler, Chiara M L; Middeke, Jan Moritz; Mueller, Martha-Lena; Oellerich, Thomas; Risse, Benjamin; Scherag, André; Schliemann, Christoph; Scholz, Markus; Spang, Rainer; Thielscher, Christian; Tsoukakis, Ioannis; Kather, Jakob Nikolas (2023).  An overview and a roadmap for artificial intelligence in hematology and oncology. Journal of Cancer Research and Clinical Oncology, 149(10):7997-8006.

Yamada, Yoshito; Nguyen, Tuan Thanh; Impellizzieri, Daniela; Mineura, Katsutaka; Shibuya, Rintaro; Gomariz, Alvaro; Haberecker, Martina; Nilsson, Jakob;  Nombela-Arrieta, César; Jungraithmayr, Wolfgang; Boyman, Onur (2023). Biased IL-2 signals induce Foxp3-rich pulmonary lymphoid structures and facilitate longterm lung allograft acceptance in mice. Nature Communications, 14(1):1383.

Mamot, Christoph;  Wicki, Andreas; Hasler-Strub, Ursula; Riniker, Salome; Li, Qiyu; Holer, Lisa; Bärtschi, Daniela; Zaman, Khalil; von Moos, Roger; Dedes, Konstantin J;  Boos, Laura A ; Novak, Urban; Bodmer, Alexandre; Ritschard, Reto; Obermann, Ellen C; Tzankov, Alexandar; Ackermann, Christoph; Membrez-Antonioli, Véronique; Zürrer-Härdi, Ursina; Caspar, Clemens B; Deuster, Stefanie; Senn, Martin; Winterhalder, Ralph; Rochlitz, Christoph (2023).  A multicenter phase II trial of anti-EGFR-immunoliposomes loaded with doxorubicin in patients with advanced triple negative breast cancer. Scientific Reports, 13(1):3705.

Guckenberger, Matthias; Guninski, Ricarda Stella; Hüllner, Martin; Kobe, Adrian; Schaser, KlausD;  Wicki, Andreas (2023).  Aktuelle interdisziplinäre Behandlung von Knochenmetastasen. Die Onkologie, 29(3):222-229.

Benoit, Tobias Matthieu; Gundermann, Stefan (2023). Teufel mit Engelsflügeln – wenn Vitamin A Leben rettet. Deutsche Medizinische Wochenschrift, 148(7):396-399.

Caiado, Francisco; Kovtonyuk, Larisa V; Gonullu, Nagihan G; Fullin, Jonas; Boettcher, Steffen; Manz, Markus G (2023). Aging drives Tet2+/− clonal hematopoiesis via IL-1 signaling. Blood, 141(8):886903.

Planas-Paz, Lara; Pliego-Mendieta, Alicia; Hagedorn, Catherine; Aguilera-Garcia, Domingo; Haberecker, Martina; Arnold, Fabian; Herzog, Marius; Bankel, Lorenz; Guggenberger, Roman; Steiner, Sabrina; Chen, Yanjiang; Kahraman, Abdullah; Zoche, Martin; Rubin, Mark A; Moch, Holger; Britschgi, Christian; Pauli, Chantal (2023).  Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma. EMBO Molecular Medicine:e16863.

Isenegger, Larissa Viviana . Phenotypic and Functional Validation of an in vitro Candidate Kinase Inhibitor Screen in Clear Cell Sarcoma. 2023, University of Zurich, Medizinische Fakultät.

Konrat, Judith; Rösler, Wiebke; Roiss, Michael; Meier-Abt, Fabienne; Widmer, Corinne C; Balabanov, Stefan; Manz, Markus G; Zenz, Thorsten (2023). BRAF inhibitor treatment of classical hairy cell leukemia allows successful vaccination against SARSCoV-2. Annals of Hematology, 102(2):403-406.

Ring, Alexander; Nguyen-Sträuli, Bich Doan; Wicki, Andreas; Aceto, Nicola (2023). Biology, vulnerabilities and clinical applications of circulating tumour cells. Nature Reviews Cancer, 23(2):95-111.

Lucaroni, Laura; Georgiev, Tony; Prodi, Eleonora; Puglioli, Sara; Pellegrino, Christian; Favalli, Nicholas; Prati, Luca;  Manz, Markus G; Cazzamalli, Samuele; Neri, Dario; Oehler, Sebastian; Bassi, Gabriele (2023).  Cross-reactivity to glutamate carboxypeptidase III causes undesired salivary gland and kidney uptake of PS-

MA-targeted small-molecule radionuclide therapeutics. European Journal of Nuclear Medicine and Molecular Imaging, 50(3):957-961. Grob, Tim; Sanders, Mathijs A; Vonk, Christian M; Kavelaars, Fran ҫ ois G; Rijken, Melissa; Hanekamp, Diana W; Gradowska, Patrycja L; Cloos, Jacqueline; Fløisand, Yngvar; van Marwijk Kooy, Marinus;  Manz, Markus G; Ossenkoppele, Gert J; Tick, Lidwine W; Havelange, Violaine; Löwenberg, Bob; Jongen-Lavrencic, Mojca; Valk, Peter J M (2023).  Prognostic Value of FLT3-Internal Tandem Duplication Residual Disease in Acute Myeloid Leukemia. Journal of Clinical Oncology, 41(4):756-765.

Adenaeuer, Anke; Barco, Stefano;  Trinchero, Alice; Krutmann, Sarah; Nazir, Hanan Fawzy; Ambaglio, Chiara; Rocco, Vincenzo; Pancione, Ylenia; Tomao, Luigi; Ruiz-Sáez, Arlette; Echenagucia, Marion; Alesci, Sonja; Sollfrank, Stefanie; Ezigbo, Eyiuche D; Häuser, Friederike; Lackner, Karl J; Lämmle, Bernhard; Rossmann, Heidi (2023).  Severe high-molecular-weight kininogen deficiency: clinical characteristics, deficiency–causing KNG1 variants, and estimated prevalence. Journal of Thrombosis and Haemostasis, 21(2):237-254.

Mansouri, Larry; Thorvaldsdottir, Birna; Sutton, Lesley-Ann; Karakatsoulis, Georgios; Meggendorfer, Manja; Parker, Helen; Nadeu, Ferran; Brieghel, Christian; Laidou, Stamatia; Moia, Riccardo; Rossi, Davide; Catherwood, Mark; Kotaskova, Jana; Delgado, Julio; Rodríguez-Vicente, Ana E; Benito, Rocío; Rigolin, Gian Matteo; Bonfiglio, Silvia; Scarfo, Lydia; Mattsson, Mattias; Davis, Zadie; Gogia, Ajay; Rani, Lata; Baliakas, Panagiotis; Foroughi-Asl, Hassan; Jylhä, Cecilia; Skaftason, Aron; Rapado, Inmaculada; Miras, Fatima; Martinez-Lopez, Joaquín;  Zenz, Thorsten; et al (2023).  Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY. Leukemia, 37(2):339-347.

Ritter, Alexander; Meier, Julia; Angst, Florian;  Rösler, Wiebke; Seeger, Harald (2023).  Erdheim-Chester disease: hairy kidney and coated aorta. Kidney International, 103(2):431.

Sava, Mihaela; Bättig, Veronika; Gerull, Sabine; Passweg, Jakob R; Khanna, Nina; Garzoni, Christian;  Gerber, Bernhard;  Mueller, Nicolas J;  Schanz, Urs;  Berger, Christoph; Chalandon, Yves; van Delden, Christian; Neofytos, Dionysios; Stampf, Susanne; Franzeck, Fabian C; Weisser, Maja (2023). Bloodstream infections in allogeneic haematopoietic cell recipients from the Swiss Transplant Cohort Study: trends of causative pathogens and resistance rates. Bone Marrow Transplantation, 58(1):115-118.

Koch, Christian; Fleischer, Juliane; Popov, Todor; Frontzek, Karl; Schreiner, Bettina; Roth, Patrick;  Manz, Markus G; Unseld, Simone; Müller, Antonia M S;  Russkamp, Norman F (2023).  Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report. Journal for ImmunoTherapy of Cancer, 11:e006059.

Dertschnig, Simone; Gergely, Peter; Finke, Jürgen; Schanz, Urs; Holler, Ernst; Holtick, Udo; Socié, Gérard; Medinger, Michael; Passweg, Jakob; Teshima, Takanori; Stylianou, Christos; Oehen, Stephan; Heim, Dominik; Bucher, Christoph (2023).  Mocravimod, a Selective Sphingosine-1-Phosphate Receptor Modulator, in Allogeneic Hematopoietic Stem Cell Transplantation for Malignancy. Transplantation and Cellular Therapy, 29(1):41.e1-41.e9.

Benoit, Tobias Matthieu; Gundermann, Stefan (2023).  53-jähriger Patient mit unklarer Anämie und Hyperkalzämie. Deutsche Medizinische Wochenschrift, 148(1-02):15-16.

Nilius, Henning; Cuker, Adam; Haug, Sigve; Nakas, Christos; Studt, Jan-Dirk; Tsakiris, Dimitrios A; Greinacher, Andreas; Mendez, Adriana; Schmidt, Adrian; Wuillemin, Walter A; Gerber, Bernhard; Kremer Hovinga, Johanna A; Vishnu, Prakash; Graf, Lukas; Kashev,

Alexander; Sznitman, Raphael; Bakchoul, Tamam; Nagler, Michael (2023). A machine-learning model for reducing misdiagnosis in heparin-induced thrombocytopenia: A prospective, multicenter, observational study. eClinicalMedicine, 55:101745.

Christ, Sebastian M; Heesen, Philip; Muehlematter, Urs J; Pohl, Kaspar; William Thiel, Gabriel; Willmann, Jonas; Ahmadsei, Maiwand; Kroese, Tiuri E; Mayinger, Michael; Balermpas, Panagiotis;  Wicki, Andreas; Andratschke, Nicolaus; Huellner, Martin;  Guckenberger, Matthias (2023).  Recognition of and treatment recommendations for oligometastatic disease in multidisciplinary tumor boards. Clinical and Translational Radiation Oncology, 38:123-129.

Rovó, Alicia; Gavillet, Mathilde; Drexler, Beatrice; Keller, Peter; Schneider, Jenny Sarah; Colucci, Giuseppe; Beauverd, Yan; van Dorland, Hendrika Anette; Pollak, Matthias; Schmidt, Adrian; De Gottardi, Andrea;  Bissig, Marina; Lehmann, Thomas; Duchosal, Michel A; Zeerleder, Sacha (2023).  Swiss Survey on current practices and opinions on clinical constellations triggering the search for PNH clones. Frontiers in Medicine, 10:1200431.

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