The anti-apoptotic protein bcl2 expression is associated with treatment failure in elderly patients (pts) with DLBCL (Blood 101:4279,2003). The ACVBP regimen with conventional consolidation therapy (JCO 18:3025,2000) yield a 2-year (yr) EFS at 71% in DLBCL pts aged 60 yrs or less with only 1 adverse age-adjusted International-Prognostic-Index factor (LI risk pts). To assess if ASCT reduces treatment failure in these pts, we initiated a trial stratified by bcl2 expression. Centralized staining for bcl2 was prospectively performed within 6 weeks after inclusion. Induction regimen consisted of 4 courses of ACVBP given every 2 weeks. In case of response, bcl2 negative pts received the conventional consolidation regimen, whereas bcl2 positive pts underwent peripheral blood stem cell collection after the 4th cycle, and ASCT (mitoxantrone 45 mg/m2, cyclophosphamide 1.5 g/m2 x 4d, etoposide 250 mg/m2 x 4d and carmustine 300 mg/m2) between d80 and d90. From 1999 to 2002, 272 LI-risk pts aged 18 to 59 (median 46, M/F=1.4) presented with bcl2 overexpression (151) or without (121). There was no difference in initial characteristics, toxicity of induction and complete response (CR+CRu) rates between bcl2 positive and bcl2 negative pts (78% and 82%, respectively, p = 0.38). ASCT was not performed in 35 pts, mainly because of early failure (37%). Although bcl2 negative pts retained a better 2-yr survival than bcl2 positive pts (95% vs. 86%, p=0.01) with a median follow-up of 21 months, 2-yr EFS and 2-yr DFS did not differ significantly (84% vs. 79%, p=0.33, and 89% vs. 87%, p=0.94 respectively). This analysis demonstrates the feasibility of taking bcl2 expression into account for the design of multicentre protocol. The lack of difference in EFS and DFS between bcl2 positive pts who received ASCT and bcl2 negative pts treated with conventional consolidation suggested that ASCT may overcome the adverse prognostic value of bcl2 expression in LI-risk pts who achieve CR or Cru.

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