Table 1. Most Common Subtypes of Non-Hodgkin’s Lymphoma Lymphoma subtype Cases Diffuse large B-cell 31% Follicular 22% Small lymphocytic/chronic lymphocytic leukemia 6% Mantle cell 6% Peripheral T-cell 6% Marginal zone B-cell (MZL) 5% Mucosa-associated lymphoid tissue 5% Remaining subtypes: <2% Splenic MZL Lymphoblastic Nodal MZL AIDS-related B-cell Burkitt’s Mycosis fungoides/Sézary syndrome Established treatment guidelines provided by the National Comprehensive Cancer Network based on the Non-Hodgkin’s Lymphoma Project. Sources: References 3 and 6.
Figure. Ann Arbor Staging System for Lymphoma
Adapted from the American Cancer Society website.
the disease who may require intermittent therapy over an extended period of time. Few subtypes of the disease are considered curable, but most are considered highly treatable. Therefore, familiarity with the nomenclature, diagnostic evaluation, staging criteria, treatment selection, and toxicity management is critical to selection of the most effective therapy for each individual patient throughout the disease continuum. Robust scientific discoveries over the past decade have led to an improved understanding of the pathobiology of the disease, including molecular characteristics, which have provided novel targets for treatment. Effective management of the patient using a life-span approach provides the opportunity to preserve future treatment options and reduce potentially debilitating toxicities. This is the first in a series of articles that will explore recent advances in the diagnosis, risk stratification, and treatment of NHL.
Disease nomenclature NHL arises from either B or T lymphocytes. B-cell NHL is the most common type (90%). Until recently, the International Working Formulation was used to describe NHL based on morphology, immunophenotyping, and clinical features. The subtypes were further divided into low-grade, intermediOctober/November 2008
ate-grade, and high-grade lymphomas. The World Health Organization
Staging and prognostic criteria Prognosis for NHL varies widely based on information obtained during the diagnostic process. Successful treatment of NHL is based on a complete evaluation of the disease, including location and extent of organ involvement and an adequate tissue
Table 2. Prognostic Indexes for Non-Hodgkin’s Lymphoma International Prognostic Index Risk factors (1 point each) Age >60 years Ann Arbor stage III or IV >1 extranodal site Elevated LDH ECOG PS ≥2
Score 0-1 2 3 4-5 0
CR (%) 87 67 55 44 92
5-year survival (%) 73 51 43 26 83
Age-adjusted risk for >60 years Ann Arbor stage III or IV Elevated LDH ECOG PS ≥2
1 2 3
78 57 46
51 26 32
Follicular Lymphoma International Prognostic Index (FLIPI) Risk factors (1 point each) Score 5-year 10-year survival (%) survival (%) Age >60 years 0-1 73 71 Ann Arbor stage III or IV 2 51 51 Hgb <12 g/dL ≥3 43 36 Elevated LDH 26 LDH indicates lactic dehydrogenase; ECOG, Eastern Cooperative Oncology Group; Hgb, hemoglobin.
diagnosis. It is generally accepted that a fine-needle aspirate is not adequate for accurate characterization of newly diagnosed NHL based on the distinct variations among each subtype. Specific elements of the tissue diagnosis and radiologic imaging will be reviewed in detail in subsequent articles in this series. The Ann Arbor staging classification system (Figure) is used for describing distribution and number of nodal sites, the presence or absence of extranodal sites, or constitutional symptoms. Two systems have been developed to provide key prognostic factors–the International Prognostic Index (IPI) for aggressive lymphoma and the Follicular Lymphoma International Prognostic Index for follicular lymphoma, which is the most common subtype of indolent NHL (Table 2).7,8 These systems are effective in identifying high-risk patients within each diagnostic subgroup who may require more aggressive initial therapy.2 The IPI system is further subdivided by age.
(WHO) revised the classification system in 2001 with added criteria based on morphology, immunophenotyping, molecular characteristics, and cytogenetics with 35 subtypes of NHL described.2 The International Lymphoma Classification Project evaluated 1403 patients thought to have NHL across nine international practice sites. After expert hematopathology review, 25 of these patients were found not to have NHL, emphasizing the complexity of accurate diagnosis in this disease. Based on the 1378 evaluable patients, the 13 most common subtypes of NHL were identified. Epidemiological studies investigating the recent increase in incidence for NHL also report a number of cases that were reclassified after further expert pathology review.4,5 Many of the subtypes described in the WHO criteria were not found in this analysis, underscoring the number of rare entities classified as NHL. In addition, this underscores the importance of including these subsets in clinical trials to further characterize the disease, develop standardized criteria for diagnosis and response evaluation, and facilitate development of new therapies. The National Comprehensive Cancer Network Guidelines for 2008 are focused on the 13 most common histological subtypes of NHL based on this analysis (Table 1).3,6
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Summary NHL represents a group of hematologic diseases that are common, have a wide variation in prognosis, and may require treatment over many years. Treatment for each stage and subtype of disease may vary, and treatment within a specific subtype may vary based on prognostic evaluation. Familiarity with the nomenclature for the subtypes of this disease and the prognostic and staging criteria will provide the foundation for effective nursing management and education of the patient with NHL. Future articles in this series will provide evaluation of specific elements of the tissue diagnosis and radiologic imaging and how these are used to select the most effective therapy for an individual patient with NHL. References 1. American Cancer Society. Cancer Facts & Figures 2008. Atlanta, GA: American Cancer Society. Available at: http://www.cancer.org/ downloads/STT/2008CAFFfinalsecured.pdf. Accessed July 30, 2008. 2. Ansell SM, Armitage J. Non-Hodgkin lymphoma: diagnosis and treatment. Mayo Clin Proc. 2005;80:1087-1097. 3. Armitage JO, Weisenberger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histological subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol. 1998;16:2780-2795. 4. Clarke CA, Glaser SL, Dorfman RF, et al. Expert review of non-Hodgkin’s lymphomas in a population-based cancer registry: reliability of diagnosis and subtype classifications. Cancer Epidemiol Biomarkers Prev. 2004;13:138-143. 5. Turner JJ, Hughes AM, Kricker A, et al. WHO non-Hodgkin’s lymphoma classification by criterion-based report review followed by targeted pathology review: an effective strategy for epidemiology studies. Cancer Epidemiol Biomarkers Prev. 2005;14:2213-2219. 6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin’s Lymphoma, v3, 2008. http://www.nccn.org/professionals/physician_gls/ PDF/nhl.pdf. Accessed July 30, 2008. 7. Solal-Céligny P, Roy P, Colombat P, et al. Follicular lymphoma international prognostic index. Blood. 2004;104:1258-1265. 8. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329:987-994.
Source: Reference 7.
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