Follicular Lymphoma: A retrospective study ( 68 cases)

1. Follicular Lymphoma: A retrospective study (68 cases) M. BENDARI, M. Rachid, S. Marouane, A. Quessar, S. Benchekroun Department of Hematology-Oncology pediatric Hospital 20 Aout, CHU IbnRochd Casablanca.

2. Background • Follicular lymphomas (FL) :30% of malignant non-Hodgkin B Lymphoma. • They are indolent. • The cells of FL express surface immunoglobulin more frequently IgM. • CD5-, CD23-/+, CD43-, CD 10+, and CD11c-. • Translocation (14.18).

3. Background • Incurable disease. • The transformation into an aggressive lymphoma diffuse B cell is possible. • No chemotherapy regimen for first-line therapy of FL has been established as a standard regimen worldwide.

4. Purpose • The aim of this study is to investigate the epidemiology and clinical evolution of patients followed in our department.

5. Materials and methods: • Descriptive study including all patients with FL treated between January 2004 and December 2011 • Follicular lymphoma of any histological grade expressing. The diagnosis was done by histological study of lymph biopsy or primary lesion biopsy. • Histological type according to WHO classification. • Pathologic diagnostic obtained by standard staining procedures and immunohistochemical analysis comprising a panel of antibodies.

6. Materials and methods: • The staging was systematically done : • Physical exam • Blood test • Chest X ray • Abdominal ultrasonography • CT scan • Bone marrow biopsy • LDH • Pre- therapeutic exam: • liver and kidney fonction • serology : HIV, HVB, HVC

7. Materials and methods • Each patient received a FLIPI score based on: • Age < 60 vs. 60 • Hemoglobin level ≥ 12g/dLvs. < 12g/dL • Serum LDH level ≤ ULN vs. > ULN • Ann Arbor stage I – II vs. III – IV • Number of nodal sites involved ≤ 4 vs. > 4

8. Materials and methods: • Positif diagnosis: histologicalstudy

9. Histopathology Follicularlymphomashowingcharacteristic pattern of closelypacked nodules withsome variation in size and shape

10. GRADING Grade 1 Grade 2 Grade 3

11. Panel of antibodies: CD20, CD5, CD10, Bcl 2, Bcl 6.

12. Materials and methods :Treatment • Therapeutic decision : • Localised Stage : abstention or radiotherapy • Advanced Stage , Bulkylesion : treatmentisnecessary • Use of Rituximab in maintenance therapy

13. Materials and methods: evolution Clinical response criteria: • Disease response and progression : physical examination and scannography : • Before chemotherapy, • After 3 or 4 cycles of therapy • At the end of chemotherapy. • A complete remission : • Resolution of all palpable peripheral adenopathy, • Disappearance of imaging evidence of disease and of all disease related symptoms, • Normalization of the standard biochemical abnormalities assignable to the lymphoma.

14. Materials and methods: Statistical analysis: • Follow-up time was calculated using Kaplan-Meier, after completion of therapy • Patients were followed every 3 months. • Progression-free survival (PFS) was calculated from entry into the study until disease progression in patients with CR or PR.

15. Results • Characteristics of patients: N 68

16. Results: Grading Histological grade The grade was not specified in 6 cases

17. Results: N 68 % Bulkylesion • <5 cm 55 80 • 5 – 10 cm 11 16 • >10 cm 2 3 LDH hight 30 44 Bonemarrow Negative 35 51,5 Positive 33 48,5

18. Results: Ann Arbor classification

19. Results One patient could not be classified because of insufficient data

20. Treatment 10 patients died or were lost to follow-up before treatment

21. Treatment : chemotherapy

22. Response to treatment

23. Responseconcording to therapy

27. Discussion • Follicularlyphoma: is one of the mostcommon types of Non Hodgkin’sLymphomas (~ 20-25%)

28. Discussion • FL: 2004 – 2011 : 68 cases / 1600 NH L ( ~ 4%)

30. Discussion Incidence : 6% vs 25% in literature report ? • Delay to diagnosis? • Transformedforms? • ethnicparticulatity of ourregion

31. Molecularbiology : • Transformedforms • DLBCL • National LymphomaRegister

32. Discussion FL : indolent lymphoma / incurable disease Treatment ? no consensus exists as to the optimal selection or sequence of availableregimens

33. In the past : • Alkylant: Clorambucil, Cyclofosphamid • Radiotherapy • Anthracycline ( CHOP) • Interféron-alpha • Fludarabine • Auto or allogeneic stem cell transplantation • Rituximab(alone , withchemotherapy or on maintenance therapy)

34. Rituximab • The addition of Rituximab to chemotherapy potentiates of the antitumor effect of chemotherapy. • Recently, it has been shown, that Rituximab has a clear benefit.

35. Rituximab : CVP versus rituximab + CVP Time to progression, relapse or death Marcus R, JCO 2008

36. Rituximab FL2000: Event-free survival (medianfollow-up 60 months) Salles G, Blood 2008

37. Rituximab : maintenance therapy • The use of Rituximab for maintenance therapy is well tolerated and improved overall survival Ghielmini M, et al. J ClinOncol 2010

38. Conclusion • The FL is typically indolent lymphoma: • Successive relapses, • Decreasing chemosensitivity, • Shorter duration of remission, with successive courses of chemotherapy. • Significant improvement in outcome for patients with FL has been accomplished in recent years especially with use of Rituximab combined to chemotherapy.

39. Conclusion: • The treatment of patients with FL must be adapted to the patient’s individual status depending on the aggressiveness of the disease. • In Casablanca: low incidence/ Heterogeneoustherapy ( CVP / CHOP): Try to establish a standard regimenincludingRituximab • Maintenance therapywithRituximab: increasinglyused • Necessary to have a National Registerincluding all cases of lymphomastreating in all Moroccancenters. • Maghreb Register of lymphoma