1. MANAGEMENT OF MANTLE CELL LYMPHOMA IN TUNISIA R BEN LAKHAL, L KAMMOUN, K ZAHRA, S KEFI Sousse 25 MAY 2012

2. MCL uncommon lymphoma Armitage JO, et al. J Clin Oncol. 1998;16:2780-2795. Diffuse large B cell: 31% Follicular: 22% Marginal zone, extranodal: 8% Peripheral T cell: 7% Small lymphocytic/CLL: 7% Mantle cell: 6% Mediastinal large B cell: 2% Anaplastic large cell: 2% Burkitt: 2% Marginal zone, nodal: 2% T lymphoblastic: 2% Other: 9%

3. Introduction Mantel Cell Lymphoma (MCL) : Aggressive B-cell Malignancy. Complex pathophysiology : t(11, 14)  aberrant expression of cylcin D1. Advanced non-bulky disease. Diagnosed at age 60 to 65 years. Short median survival (3 years) despite intensive therapy.

4. OBJECTIVE Retrospective Tunisian multicenter study : Analyze epidemiological,clinical and biological features of tunisian MCL patients. Evaluate the response to treatement according to classical prognostic factors. Analyze the event free survival (EFS) and the overal survival (OS) according to prognostic factors

5.  32 patients : 2000-2011  3 centers :  Tunis : 20 patients  Sousse : 7 patients  Sfax : 5 patients PATIENTS

6. Epidémiologic Features Annual incidence of MCL

7. Epidémiologic Features Median age : 62 years ( 30-84 years) 23 males ( 72%) Sex-ratio : 2.55

8. Clinical and biological features NPencentage B symptoms No2062.5% Yes1237.5% PS  2 2372% >2928% Stage Early518% Advanced2784% LDH >Nle2166% <Nle1134% Bone Marrow involvement Yes1960% No1340%

9. Prognosis of patients NPercentage IPI 0-11238 2-32062 MIPI (16 cases) Low risk319 Intermediate531 High risk850

10. Methods STATISTIC STUDY STATISTIC STUDY 1- Predictives response factors : ( Chi-square test, p < 0.05 ) 2 - The EFS «event free survival» and the OS «overall survival» : (Kaplan-Meier method and Log-Rank test) - Univariate study - Multivariate study

11. Treatment Features 30 patients treated (1death, 1 lost to follow-up) 25/30 patients received Rituximab (83%) 2 patients treated on 2001 3 patients > 75 years (Mini-CEOP) Chemotherapy : CHOP/DHAP = 12 patients ( 40%) CHOP = 13 patients ( 43.3%) Velcade – CHP = 2 patients (6.6%) Mini-CEOP = 3 patients ( 10%) Autologous stem cell transplantation = 5 patients (13pts<60 years) Allogeneic stem cell transplantation : 1 patient

12. Response of Treatment 30 patients treated 4 lost to follow-up (13 %) 26 evaluables patients CR 11 patients (42%) PR 07 patients (27%) Failure/progression 08 patients (31%) ORR = 69% 6 Deaths (4 toxic deaths)

13. Gender :ORRP Male68.4% 0.88 NS Female71.4% Stage : Early100% 0.13 NS Advanced61.9% LDH: N72.7% 0.94 NS >N71.4% PS :  2 70% 0.84 NS >275% Response according to prognostic factors

14. ORRP IPI : 0-172.7% 0.85 NS 2-369.2% Auto : Yes100% 0.2 NS No65% Rituximab : Yes72.7% 0.37 NS No50% DHAP: Yes81.8% 0.23 NS No60% Response according to prognostic factors

15. OVERALL SURVIVAL (OS) OS : 60% (5years)

16. OS according to prognostic factors One significant adverse prognostic factor : failure to treatement OR Failure

17. Event free survival (EFS) EFS(5years) : 52%

18. DEATHS : 8 patients 1 death before treatement 5 toxic deaths 2 deaths progression RELAPSES One relapse Late relapse (5 years) Post ASCT

19. DISCUSSION Epidemiological, clinical and biological characteristics of Tunisian patients are comparables to littérature data. annual incidence increasing ? or improvement of diagnosis tools ?

20. DISCUSSION  There is no generally established prognostic index for patients with MCL.  For our patients : IPI>2 (High risk patients) : 20 (62%) MIPI evaluated in 16 patients High risk patients : 8 (50%) PROGNOSIS

21. MIPI > FLIPI > IPI

22. Biologic MIPI = MIPI + proliferation marker Ki-67

23. DISCUSSION Aggressive therapies including chemo-immunotherapy or high dose chemotherapy followed by autologous stem cell transplant have been shown to improve outcome BUT no standard therapy offers the potential for cure.  Our patients : Immunotherapy : all younger patients RCHOP/RDHAP : 12 patients ASCT : only 5 patients (13 pts < 60 yrs) ORR : 69% (DHAP : ORR at 80%) OS : 60% EFS : 52% TREATMENT

26. Role of cytarabine (Ara-C)

27. Role of ASCT

28. CONCLUSION Epidemiological, clinical and biological characteristics of Tunisian patients are comparables to littérature data. Therapeutic results must be improved +++ Younger patients (< 60 yrs) : HD Arac + ASCT Patients <40yrs : allogeneic transplantation Older patients : RCHOP +/- Rituximab maintenance Salvage therapy +++ Better management of toxicity