M. BENDARI, M. Rachid, S. Marouane, A. Quessar, S. Benchekroun Department of Hematology-Oncology pediatric Hospital 20 Aout, CHU Ibn Rochd Casablanca.

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).

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.

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

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.

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

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

Materials and methods: Positif diagnosis: histological study

Histopathology Follicular lymphoma showing characteristic pattern of closely packed nodules with some variation in size and shape

GRADING Grade 2 Grade 3 Grade 1

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

Materials and methods :Treatment Therapeutic decision :  Localised Stage : abstention or radiotherapy  Advanced Stage, Bulky lesion : treatment is necessary  Use of Rituximab in maintenance therapy

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.

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.

Results Characteristics of patients: N 68 N68 Sex-Ratio M/F2 Median of age57 years ( 28 – 77) Mean delay to doagnosis8 months ( months) Clinical présentationasymptomatic6 (9%) Fatigue10 (14%) Peripheral lymph nodes 20 (30%) B symptoms32 (47%)

Results: Grading Grade 1 28 cases (41%) Grade 2 25 cases (36%) Grade 3 3a: 3 cases 3b: 6 cases Histological grade The grade was not specified in 6 cases

Results: N68% Bulky lesion <5 cm – 10 cm1116 >10 cm23 LDH hight3044 Bone marrow Negative 3551,5 Positive3348,5

Results: Ann Arbor classification Stage I 12 cases(17%) Stage II 8 cases (11%) Stage III 14 cases (20%) Stage IV 34 cases(50%)

Results N 68% FLIPI score Low risk17 25 Intermadiate risk35 51 High risk15 22 One patient could not be classified because of insufficient data

Treatment Radiotherapy alone:3 Abstention 8 Chemotherapy 47 Evaluable patient N/58 10 patients died or were lost to follow-up before treatment

Treatment : chemotherapy N 58 Abstention8 Radiotherapy alone3 CHOP26 CVP3 RCHOP12 RCVP6 Maintenance treatment6

Response to treatment N50 CR: 35 (70%) PR: 4(8%) Faillure:11 (22%) CR2: 3Death: 3 Lost to follow-up: 5

Response concording to therapy Radiotherapy (N3)CVP/CHOP (N29)RCVP/RCHOP (N18) CR31965%1372% PR827%211% Failure27%316%

Mean to follow-up 25 months N50 Relapse 12(24%) CR2: 3 Faillure: 5 Lost to follow- up : 4 CCR: 20 cases (40%) Lost to follow-up 18 (36%) In CR: 6 In RP: 3 In Progressing disease : 9

Discussion Follicular lyphoma: is one of the most common types of Non Hodgkin’s Lymphomas ( ~ 20-25%)

Discussion FL: 2004 – 2011 : 68 cases / 1600 NHL ( ~ 4%)

Discussion Incidence : 6% vs 25% in literature report ?  Delay to diagnosis?  Transformed forms?  ethnic particulatity of our region

 Molecular biology : Transformed forms DLBCL  National Lymphoma Register

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

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

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.

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

Rituximab FL2000: Event-free survival (median follow-up 60 months) Salles G, Blood 2008

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

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.

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/ Heterogeneous therapy ( CVP / CHOP): Try to establish a standard regimen including Rituximab  Maintenance therapy with Rituximab: increasingly used  Necessary to have a National Register including all cases of lymphomas treating in all Moroccan centers.  Maghreb Register of lymphoma