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NON HODGKIN’S LYMPHOMA

NON HODGKIN’S LYMPHOMA. Sec C Group D. Non-Hodgkin’s Lymphoma. NHL is a heterogenous group of lymphoproliferative malignancies with differing patterns of behavior and responses to treatment. It usually originates in the lymphoid tissues and can spread to other organs.

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NON HODGKIN’S LYMPHOMA

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  1. NON HODGKIN’S LYMPHOMA Sec C Group D

  2. Non-Hodgkin’s Lymphoma • NHL is a heterogenous group of lymphoproliferative malignancies with differing patterns of behavior and responses to treatment. • It usually originates in the lymphoid tissues and can spread to other organs. • Separated from Hodgkin’s disease by the recognition of the Reed-Sternberg cells. • However, unlike Hodgkin disease, NHL is much less predictable and has a far greater predilection to disseminate to extranodal sites.

  3. Non-Hodgkin ‘s Lymphoma • It can occur at any age and are often marked by lymph nodes that are larger than normal, fever, and weight loss. • There are many different types of non-Hodgkin lymphoma. • These types can be divided into: • Aggressive (fast-growing) types • Indolent (slow-growing) types • They can be formed from either B-cells or T-cells. • Most NHLs are of B-cell origin. • The prognosis depends on the histologic type, stage, and treatment.

  4. Indolent lymphomas Aggressive Lymphomas It has a shorter natural history, but a significant number of these patients can be cured with combination chemotherapy regimens. • Relatively good prognosis, with median survival time as long as 10 years, but they are not usually curable in advanced stages. • Early-stage (I and II) indolent NHL can be treated effectively with radiation therapy alone. • Most of the indolent types are nodular (or follicular) in morphology.

  5. B-cell non-Hodgkin lymphomas T-cell non-Hodgkin lymphomas Mycosis fungoides Anaplastic large cell lymphoma Precursor T-lymphoblastic lymphoma • Burkitt lymphoma • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) • Diffuse large B-cell lymphoma • Follicular lymphoma • Immunoblastic large cell lymphoma • Precursor B-lymphoblastic lymphoma • Mantle cell lymphoma

  6. General Aspects of Lymphoid Malignancies Fauci, et al., 2008. Harrison’sPrinciples of Internal Medicine, 17th ed.US:Mcgraw Hill, p. 687

  7. Non-Hodgkin’s Lymphoma • Incidence and patterns of expression of subtypes differ geographically • Asia – T cell lymphoma • Western countries – B cell (follicular) lymphoma • Southern Asia & Latin America – Angiocentric nasal T/NK lymphoma • Southern Japan & Carribean – Adult T cell Lymphoma (HTLV – 1) Fauci, et al., 2008. Harrison’sPrinciples of Internal Medicine, 17th ed.US:Mcgraw Hill, p. 688

  8. Non-Hodgkin’s Lymphoma • Environmental Factors: • Infectious agents • Chemical exposures • Medical treatments Fauci, et al., 2008. Harrison’sPrinciples of Internal Medicine, 17th ed.US:Mcgraw Hill, p. 688

  9. Non-Hodgkin’s Lymphoma • Infectious agents associated with the development of Lymphoid Malignancies Fauci, et al., 2008. Harrison’sPrinciples of Internal Medicine, 17th ed.US:Mcgraw Hill, p. 688

  10. Non-Hodgkin’s Lymphoma • Diseases or exposures associated with increased risk of development of malignant lymphoma Fauci, et al., 2008. Harrison’sPrinciples of Internal Medicine, 17th ed.US:Mcgraw Hill, p. 688

  11. Immunology • All lymphoid cells are derived from a common hematopoietic progenitor • Sequential activation of a series of TF’s, cells becomes committed to the lymphoid lineage  T and B cells

  12. B cells development • A cell becomes committed to the B cell development  arrangement of immunoglobulin genes

  13. T cell development • A cell becomes committed to T cell differentiation • upon migration to the thymus • Reaarangement of T cell antigen genes

  14. Malignancies • Associated with recurring genetic abnormalities • At a variety of chromosomal changes  • Gross (translocations, additions or deletions) • Rearrangement of specific genes • Underexpression • Mutation of specific oncogenes

  15. Chromosomal translocations • Antigen receptor genes • Immunoglobulin genes on Chr. 2, 14, and 22 on B cells • T cell antigen genes on chr. 7 and 14 in T cells. • Rearrangement to generate mature antigen receptors  create a site vulnerability to abnormal recombination

  16. Non-Hodgkins Lymphoma Clinical features

  17. Non-Hodgkins Lymphoma -heterogenous group of lymphoproliferative malignancies with differing patterns of behavior and responses to treatment -originates in the lymphoid tissues and can spread to other organs -More common in elderly and males http://emedicine.medscape.com/article/202677-overview Harrison’s Principle of Internal Medicine 17th edition

  18. Lymphadenopathy • the most common manifestation of lymphoma • Waldeyer ring &mesenteric Lymph nodes are commonly involved • Spreads in noncontiguous fashion Robbins & Cotran Pathologic Basis of Diseases, 7th edition p. 686

  19. Lymphadenopathy • 2/3 of NHL (and virtually all cases of HL) present with NONTEDER nodal enlargement often >2cm size that can be localized or generalized • The remaining 1/3 of NHL’s arise at extranodal sites ( e.g. skin, stomach and brain) Robbins & Cotran Pathologic Basis of Diseases, 7th edition p. 668

  20. Other Signs And Symptoms • fevers, night sweats, weight loss, and fatigue • pruritus • shortness of breath, chest pain, cough, abdominal pain and distension, or bone pain • pallor (suggesting anemia) • purpura, petechiae, or ecchymoses (suggesting thrombocytopenia) http://emedicine.medscape.com/article/202677-overview Harrison’s Principle of Internal Medicine 17th edition

  21. Robbins & Cotran Pathologic Basis of Diseases, 7th edition p. 671

  22. Robbins & Cotran Pathologic Basis of Diseases, 7th edition p. 671

  23. Robbins & Cotran Pathologic Basis of Diseases, 7th edition p. 671

  24. Lymphoid neoplasia can be suspected from all the clinical features but histological examination of lymph nodes or other involved tissues is required for the diagnosis Robbins & Cotran Pathologic Basis of Diseases, 7th edition p. 668

  25. Staging evaluation for NHL Ann Arbor Staging system is applicable to both Hodgkin’s disease and NHL

  26. Ann Arbor Staging System Source: p. 691

  27. Ann Arbor Staging System Staging for our patient: Stage III1B Source: p. 691

  28. Ancillary procedures for Primary staging • CBC • ESR • LDH • ß2- microglobulin • Serum protein electrophoresis • Chemistry studies reflecting major organ function • CT scans (chest, abdomen, pelvis) • Bone marrow biopsy Source: p. 692

  29. International Prognostic Index (IPI)for NHL • A powerful predictor of outcome in all subtypes of NHL • Scoring: based on presence or absence of • 5 adverse prognostic factors • may have none or all 5 of these Source: p. 692

  30. ECOG PERFORMANCE STATUS* http://ecog.dfci.harvard.edu/general/perf_stat.html

  31. KARNOFSKY PERFORMANCE STATUS SCALE DEFINITIONS RATING (%) CRITERIA http://www.hospicepatients.org/karnofsky.html

  32. International Prognostic Index (IPI)for NHL Source: p. 692

  33. IPI for Patient (Pre treatment)

  34. Treatment of Non- Hodgkin’s Lymphoma

  35. Precursor B cell Lymphoblastic Leukemia • Remission induction with combination therapy • Consolidation phase: • High dose systemic therapy • Treatment to eliminate CNS disease • Continuing therapy: prevent relapse and effect cure

  36. Precursor B cell Lymphoblastic Leukemia • Combination therapy used: • Rituximab- fludarabine- cyclophosphamide • Associated with grade III or IV neutropenia • Cyclophophamide- vincristine- prednisone • Cyclophosphamide- doxorubicin- vincristine- prednisone

  37. B Cell Chronic Lymphoid Leukemia/ Small Lymphocytic Leukemia • Most common: • Chlorambucil: orally; few immediate side effects • Chosen in elderly patients who require therapy • Fludarabine: IV; with significant immune suppression • more active agent; with significant incidence of complete remission • Regimens inclusive of this drug is chosen for young patients presenting with leukemiarequiring therapy • Second line agent for patients with tumors unresponsive to chlorambucin

  38. B Cell Chronic Lymphoid Leukemia/ Small Lymphocytic Leukemia • Rai stage O and Binet stage A ( no manifestations of disease other than BM involvement and lymphocytosis • Followed without a specific therapy • With adequate number of circulating normal blood cells, asymptomatic • Require treatment for the first few years of follow up

  39. B Cell Chronic Lymphoid Leukemia/ Small Lymphocytic Leukemia • Rai stage III or IV or Binet stage C (Bone Marrow failure) • Require initial therapy • Immune manifestations should be managed independently of antileukemic therapy

  40. MALT Lymphoma • Radiation and Surgery • Because it is often localized • Eradication of H. pylori infection • With more extensive diseases: Chlorambucil

  41. Mantle Cell Lymphoma • With disseminated disease: aggressive combination chemotherapy regimens+ autologous/ allogeneic BM transplantation • Localized diseases: combination chemotherapy + radiotherapy • Asymptomatic, elderly patient: observation + single- agent chemotherapy

  42. Follicular Lymphoma • Asymptomatic patient, older patient: watchful waiting • For those who require treatment: single- agent chlorambucil or cyclophosphamide or combination therapy with CVP or CHOP • For patients with localized follicular lymphoma: radiotherapy

  43. Follicular Lymphoma • Most responsive to chemotherapy and radiotherapy • Active therapies: • Fludarabine • Interferon α: prolong survival in patients on doxorubicin- containing combination therapies • Monoclonal antibodies with or without radionuclides • Lymphoma vaccines

  44. Diffuse Large B Cell Lymphoma • Initial Treatmant: combination chemotherapy regimen= CHOP + Rituximab • Stage I or non bulky stage II: 3-4 cycles + field radiotherapy • Bulky stage II, stage III, stage IV: 6-8 cycles or 4 cycles then reevaluate -> complete remission -> 2 more cycles, then therapy discontinued

  45. Diffuse Large B Cell Lymphoma • IPI : predict favorable responses • Score 0-1: 5 year survival >70 % • Score 4-5: 5 year survival ~20% • For refractory cases or relapse • Salvage therapy • Alternative combination therapy • Autologous bone marrow transplantation

  46. Burkitt’s Lymphoma • Treatment should begin 48 hrs after diagnosis • High doses of cyclophosphamide • Prophylactic therapy to CNS mandatory

  47. Hairy cell leukemia: Cladribine • Splenic marginal zone lymphoma: splenectomy, chlorambucil • Lymphoplasmacytic lymphoma: Chlorambucil, fludarabine and cladribine • Nodal marginal zone lymphoma: treatment same as follicular lymphoma

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