1. Non-Hodgkin Lymphoma March 13, 2013 Suzanne R. Fanning, DO Greenville Health System

2. Myelopoesis

3. NHL Heterogenous group of neoplastic diseases derived of monoclonal lymphocytes. B or T cell in origin Indolent vs. aggressive Characterized by morphology, immunophenotype, and genetic mutations

7. Incidence vs. mortality

10. NHL Indolent: slowing progressive lymphadenopathy cytopenias hepato/splenomegaly Aggressive: rapidly growing mass systemic B symptoms elevated LDH/uric acid

13. Pediatric NHL

14. 5 th most common malignancy <15yr 7% of pediatric cancers 800 cases/yr in the US Median age: 10 >90% stage I/II Good prognosis (OS>80%)

15. Diagnosis Excisional biopsy (not FNA) Morphology Immunophenotype Genetic studies: conventional karyotype FISH PCR (immunoglobulin gene rearrangement)

16. Histology Nodular Tends to be slow growing Diffuse Aggressive Cutaneous

17. Histology

19. Immunostains

21. DLBCL - phenotype

23. Cutaneous B cell NHL

24. Cutaneous T cell NHL

25. Risk factors Family history Prior hematologic malignancy Prior chemotherapy and/or radiation Immunosuppressive medications History of organ transplant Pesticides/Agent orange Infections

26. Hepatitis B or C HIV HTLV-1 Super rare EBV Chlamydia pisittaci Causes an ocular lymphoma  tx = doxycycline Borrelia burgdorefi Rare

27. Risk factors Autoimmune disorders Immunodeficiency disorders Mixed cryoglobulinemia Rare Multicentric Castleman’s disease Infammatory GI disorders: chron’s, celiac, H. pylori- associated gastritis

28. Presentation Painless lymphadenopathy Fatigue B symptoms: fever (>100.4) night sweats weight loss (>10%/6 mo)

29. Presentation - less common Rash Pruritus Malaise Ascites Effusion Pleural and pericardial

30. Extranodal disease 50% of cases have extranodal involvement 10-35% present as primary extranodal GI - most common Primary CNS NHL - rare

31. Extranodal sites

32. Labs CBC CMP LDH Uric acid Serum protein electrophoresis – assessment for monoclonal protein

33. Staging studies CT C/A/P (+/- neck) PET/CT scan – especially if aggressive disease Bone marrow biopsy morphology cytogenetics/FISH

36. Staging – Ann Arbor I: one lymph node group II: 2 LN groups on same side of diaphragm III: LN involvement on both sides of diaphragm IV: as above with bone marrow involvement A or B: w/ or w/o B symptoms E: extranodal

37. Lymphatic system

38. Internation Prognostic Index (IPI)

39. FLIPI Similar to IPI Appropriate for follicular NHL age stage LDH hemoglobin # of LN groups instead of extranodal groups involved

40. Treatment – Indolent NHL Asymptomatic: surveillance Symptomatic: Early stage: radiation single-agent rituxan Advanced stage: multi-agent chemotherapy

41. Cell cycle

42. Chemotherapy effects on cell cycle

43. Treatment - Indolent Chemotherapy regimens for advanced stage: R-CVP – Rituxan, cytoxan, vincristine, prednisone BR – bendamustine, Rituxan FCR – fludarabine, cytoxan, Rituxan

44. Treatment - DLBCL Early stage (I-II): R-CHOP x 3 Involved field radiation

45. Treatment - DLBCL Advance stage (III/IV): R-CHOP x 6-8 cycles

46. R-CHOP Rituxan Cytoxan Adriamycin Vicristine Prednisone

47. Rituximab

48. Rituximab/CD 20 target

49. 10-year survival

50. Gene expression profile

54. Relapsed NHL Alternate chemotherapy regimens Radiation to symptomatic regions ASCT – autologous stem cell transplant Allogeneic transplant Palliative/symptomatic care

55. Thank you! email: sfanning@ghs.org