Lymphoma

1 Guideline Resource Unit Lymphoma Clinical Practice Guideline LYHE-002 V16. Table of Contents Background Guideline Questions Search Strategy Target Population Discussion I. Diagnosis and Pathologic Classifications II. Staging III. Treatment of Non-Hodgkin Lymphomas IV. Cutaneous Lymphoma V. Hodgkin Lymphoma VI. HDCT and Hematopoietic Stem Cell Transplantation for Lymphoma VII. Supportive Care in the Treatment of Lymphoma VIII. Follow-Up Care in the Treatment of Lymphoma Appendix A (Chemotherapy Regimens). Appendix B: General Radiotherapy Guidelines Appendix C: Prognostic Models Appendix D: Lymphoma Response Criteria Appendix E: New Lymphoma Patient Data Sheet Appendix F: Ideal Body Weight Glossary of Abbreviations Dissemination Maintenance Clinical Practice Guideline LYHE-002 Background Lymphomas encompass a group of lymphoproliferative malignant diseases that originate from T- and B- cells in the lymphatic system.

2 Traditionally, lymphomas have been subcategorized into two groups: Hodgkin Lymphoma and non-Hodgkin Lymphoma . It is now known however, that Hodgkin Lymphoma is simply one of the numerous varieties of Lymphoma , and that non-Hodgkin Lymphoma is a fairly meaningless term, representing all of the other subtypes of this disease. Non-Hodgkin Lymphoma involves a heterogeneous group of over 40 lymphoproliferative malignancies with diverse patterns of behaviours and responses to treatments. Non-Hodgkin Lymphoma is much less predictable than Hodgkin Lymphoma and prognosis depends on the histologic type, stage, and treatment. In Canadian males and females, the incidence rates for non-Hodgkin Lymphoma showed a marked increase by approximately 50% between 1978 and the late 1990s, but have since stabilized1.

3 Mortality rates have followed a similar pattern. The clearest risk factor for the disease is immunosuppression associated with HIV infection, or medications used to prevent rejection in organ transplantation. Other factors that increase risk of non-Hodgkin Lymphoma are poorly understood but may include occupational exposures to pesticides, herbicides, and dioxins, as well as chronic immune stimulation associated with autoimmune disorders ( thyroiditis, Sjogren's Syndrome, SLE) or infections ( Helicobacter pylori gastritis, hepatitis C virus)2. In 2015, it is estimated that 8200 new cases of non-Hodgkin Lymphoma will be diagnosed in Canada, and 2650 deaths will occur, making non-Hodgkin Lymphoma the sixth most common cause of cancer-related death in Canada3.

4 Hodgkin Lymphoma is a malignancy characterized histopathologically by the presence of Reed- Sternberg cells in the appropriate cellular background. Although rare, Hodgkin Lymphoma is one of the best-characterized malignancies of the lymphatic system and one of the most readily curable forms of malignant The incidence rate has remained fairly steady over time, it is estimated that approximately 1000 new cases of Hodgkin Lymphoma are diagnosed in Canada each year3. It is important to note that Lymphoma also represents the most commonly diagnosed non-epithelial cancers in adolescents and young adults in Canada. Between 1992 and 2005, 5577 new cases of Hodgkin and non-Hodgkin Lymphoma were diagnosed in Canadians aged 15-29 years1.

5 The following guidelines do not address Lymphoma in the pediatric or adolescent populations. Guideline Questions What are the diagnostic criteria for the most common lymphomas? What are the staging and re-staging procedures for Hodgkin and non-Hodgkin lymphomas? What are the recommended treatment and management options for Hodgkin and non-Hodgkin lymphomas? What are the recommended follow-up procedures for patients with malignant Hodgkin and non- Hodgkin Lymphoma ? 1. Last Reviewed: September 2019 Search Strategy Medical journal articles were searched using Medline (1950 to October Week 1, 2015), EMBASE. (1980 to October Week 1, 2015), Cochrane Database of Systematic Reviews (3rd Quarter, 2015), and PubMed electronic databases.

6 An updated review of the relevant existing practice guidelines for Lymphoma was also conducted by accessing the websites of the National Comprehensive Cancer Network (NCCN), Cancer Care Ontario (CCO), the British Columbia Cancer Agency (BCCA), the European Society for Medical Oncology (ESMO), and the British Committee for Standards in Haematology. Target Population The following guidelines apply to adults over 18 years of age. Different principles may apply to pediatric and adolescent patients. References 1. Canadian Cancer Society's Steering Committee. Canadian Cancer Statistics. In. Special Topic: Cancer in Adolescents and Young Adults. Available at: ~/media/CCS/Canada%20wide/Files%20 List /English%20files%20heading/pdf%20not%20i n%20publications%20section/Stats%202009E %20 Special% hx2009.

7 2. Marcus R. Lymphoma : pathology, diagnosis, and treatment. 14th ed: Cambridge University Press; 2007. 3. Canadian Cancer Society's Steering Committee on Cancer Statistics. Canadian Cancer Statistics. In. Available at: ~/media/CCS/Canada%20wide/Files%20 List/English%20files%20. heading/PDF%20%20 Policy%20- %20 Canadian%20 Cancer%20 Statistics%20%20 English/Canadian%20 Cancer%20 Statistics%202011%20- % 2. Last Reviewed: September 2019 I. Diagnosis and Pathologic Classification 1-6. An excisional lymph node biopsy of the largest regionally involved lymph node is the optimal specimen for initial diagnostic assessment. Similarly, a sizable biopsy from the organ of origin in extranodal lymphomas is also suitable.

8 Compelling clinical contraindications to an open biopsy should be present before considering any other options. A careful clinical examination or radiological investigations for more accessible or palpable pathologic adenopathy could be useful in decision making prior to opting for a lesser diagnostic specimen. Fine needle aspirate biopsies are inadequate for the initial diagnosis of Lymphoma . These latter specimens may provide adequate material for evaluating possible relapse, clarification of staging at questionable sites and as a source of additional specimen where required for further special testing or research. Occasionally, a generous core needle biopsy comprising many core samples with sufficient material to perform the appropriate ancillary techniques required for diagnostic assessment (immunohistochemistry, flow cytometry, PCR.)

9 For IgH and TCR gene rearrangements, and FISH for major translocations) may supply adequate tissue, in cases when a lymph node is not easily accessible for excisional or incisional biopsy. A. reference Lymphoma pathologist should confirm Lymphoma diagnoses in each and every case. This is particularly important in cases when only a core needle biopsy is available, and whenever requested by the treating clinician. Table 1 describes the histologic subclassification of the malignant lymphomas, and is an adaptation of the most recent WHO classification6. This classification is based on the light microscopic interpretation complemented by special stains, immunophenotyping, cytogenetics and other ancillary information as available.

10 The specific lymphomas are divided into three major groups, according to the degree of clinical aggressiveness, for treatment planning. All B-cell lymphomas should be immuno-phenotyped to determine if they are CD20 positive. 1. Last Reviewed: July 2019 Table 1. Lymphoma classification6. B-cell T-cell Follicular, grades 1-2, 3a Small lymphocytic Lymphoma /Chronic Lymphocytic Mycosis fungoides /Sezary syndrome Leukemia Primary cutaneous, CD30+. Marginal zone, extranodal (MALT) Primary cutaneous perioheral T-cell Lymphoma Indolent Splenic marginal zone PTCL, CD30- Marginal zone, nodal (monocytoid B-cell) T-cell large granular lymphocytic leukemia Lymphoplasmacytic (Waldenstr m's macroglobulinemia). Primary cutaneous, follicle centre Hairy cell leukemia Nodular lymphocyte predominant Hodgkin Lymphoma Mantle cell (can be aggressive).