Therapeutic results of diffuse large B-Cell lymphoma N.Ait Amer; F.Tensaout; H.Moussaoui; F.Belhadri; N.Abdennebi; F.Boukhamia; D.Benali; L.Metidji; S.Zeghouati; S.Zerkout; N.Boudjerra;R.M.Hamladji; Service d’Hématologie- Greffe de moelle osseuse Centre Pierre et Marie Curie

Introduction Diffuse large B-Cell lymphoma (LDGCB) represents approximately 40% of all lymphomas and 80% of aggressive lymphomas According to the Ann Arbor classification, the localized stage (clinical stages I/II) represent 35% to 45% of cases and advanced stage (clinical stages III/IV) 55% to 65% of cases(Hématologie 2007;13(5):320-3). The possibility of treating patients is based on a very precise stading of the disease and a deep investigation of the individual pronostic factors.

Materials and Methods (1) Between the 228 patients (pts) diagnosed as LDGCB from January 2001 to december 2010; we report the out come of 196 pts treated by CHOP with the advent of Rituximab (R) or not; followed or not by radiotherapy as first line treatment. Are excluded from the study all the cerebral lymphomas, the primary mediastinal lymphomas and the bones lymphomas. For the 196 pts of this study: The median age is 57 years (16-83) The sex ratio= 1,3 (111M/85F) The median time to diagnosis : 5 months (0-48)

Materials and Methods (2) Clinical Staging: Stages Number % I 26 13 96 (49%) II 70 36 III 55 28 100 (51%) IV 45 23 Bulky disease (large tumour size ≥ 7 cm) Localized stages(96) 37 39 Advanced stages (100) 48

Materials and Methods (3) International pronostic index: has been determined in only 149/196 pts IPI Number % Low risk 56 38 Good pronostic (67%) Low-intermediate risk 44 29 High intermediate risk 26 Poor pronostic (33%) High risk 11 7

Materials and Methods (4) Therapy (1) The CHOP regimen is the combination of 750 mg/m² of Cyclophosphamide on day 1; 50 mg/m² of doxorubicin on day 1; 1,4 mg/m² of vincristine, up to a maximal dose of 2 mg on day 1; and 40 mg/m² of prednisone per day for five days. Advent or not Rituximab at a dose of 375 mg/m² on the day one of each CHOP cycle; with an average of 4 cycles of CHOP (1-8); every 3 weeks. The radiotherapy was given on the lymph-node regions involved at a dose of 40 Gy. At december 2011, the median follow up is 60 months (12 at 132)

Materials and Methods (5) Therapy (2) Advanced stage: 100 pts 59 pts received CHOP olone 41 pts received R-CHOP 28 pts among them; who are in first response after the first line therapy (CHOP ± R) underwent intensive regimens (27 pts have a high dose therapy followed by autologous stem cell transplantation [ASCT]; and 1 pt has an allogenic stem cell transplantation with a previous reduce conditionning regimen). Localized stage : 96 pts 58 pts received CHOP ± R+RT 38 pts received CHOP ± R (6pts underwent ASCT)

Results (1) Advanced Stage: 100 pts First results : CHOP (59pts) R-CHOP (41pts) P CR 35 (59%) 17 (42%) P=1,63 NS RP 05 (09%) 12 (29%) / Overall remission 40 (68%) 29 (71%) P=0,76 NS Failures 10 (17%) 10 (24%) Dead related to treatment Toxicity (TRM) 09 (15%) 02 (05%)

Results(2) Advanced stage 72/100 pts (28pts have been intensified ) Out come of their response CHOP (29pts) R-CHOP (12pts) Persistant response 08 (28%) 03 (25%) Relapse 13 (45%) 05 (42%) Death (CR) 02 (07%) 04 (33%) Losing sight pts (CR) 06 (20%) /

Results (3) Out come of the advanced stage: 72 Pts Alives CHOP : 12 (25%) R-CHOP: 08 (33%) Death CHOP: 30(63%) R-CHOP: 16(66%) Losing sight pts CHOP 48pts 1st CR 2nd CR Relapse Failure Relapse failure Toxicity 06 08 02 11 09 R-CHOP 24pts 03 04 01

EFS Advanced stage

OS Advanced stage

Results (4) Localized stage : 96 pts First results CHOP± R+RT (58pts) After CT After RT CHOP± R (38pts) P CR 40 (69%) 56 (97%) 20 (53%) P ˂ 10-5 S PR 18 (31%) 02 (03%) 03 (07%) / Overall response 58 (100%) 23 (60%) Failure 09 (24%) TRM 06 (16%)

Results (5) Localized stage: 90/96 pts (6pts have been intensified) The out come of response: Réponse Alives in CR Relapse Death Lost in sight pts CHOP ± R + RT (58 pts) 36 (62%) 14 (24%) 03 CR (05%) 05 CR (09%) (17/32 pts) 11 (65%) 04 (24%) 02 CR (11%)

Results (6) Out come of the localized stage : 90 pts Alives CHOP ± R +RT : 39 (67%) CHOP ± R : 13 (41%) Death CHOP ± R +RT: 14(24%) CHOP ± R: 17 (53%) Losing sight pts CHOP ± R +RT (58pts) 1st CR 2nd CR Relapse Failure 1st CR Relapse failure Toxicity 36 (62%) 03 / 11 05 CHOP ± R (32pts) 11 (65%) 01 08 06 02

EFS Localized stage 50% 45% 36%

OS Localized stage 66% 55%

Results (7) Out come of ASCT: 33pts Allogeneic SCT: 01 pt alives in CR at 9 months follow up. ASCT Number % Status before the transplant(33pts) CR 22 66 PR 11 34 status after transplant(33pts) 29 88 TRM 04 12 Out come of CR (29 pts) Alives in CR 21 72 Relapse 06 (5 Death- 1 alive in CR 2) Death in CR 02 07

EFS CT/ASCT

OS CT/ASCT

Conclusion The characteristics of the series : Median age 57 years(young/literature) Advanced stages= localized stages Bulky forms represent 48%of the advanced stages Good pronostic groupe represent67%/poor pronostic groupe 33% In the localized forms: The radiotherapy increased survival regardless of previous treatment CHOP with or without R (OS at 10 years 66% vs 36%) In advanced forms: ASCT increased survival significantly(OS at 10 years 56% vs 31%) Our results do not reach the literature because of the bulky forms with the percentage is important in this population:may be should we practice a more intensive therapy(ACVBP regimen)?