Abstract This study reports the final analysis of the outcome of relapsed/progressive patients who participated in the FL2000 trial. The FL2000 prospective trial evaluated the combination of rituximab with chemotherapy plus interferon as a first line treatment of follicular lymphoma (FL) patients (pts). Untreated high tumor burden pts (n=359) were randomly assigned to receive either 12 × CHVP (cyclophosphamide, adriamycin, etoposide and prednisolone) plus interferon-α2a over 18 months (Arm A) or 6 × CHVP combined with 6 × rituximab and interferon for the same time period (Arm B). The final analysis (Salles et al. ASH 2007) confirmed the superiority of Arm B. Second line treatment was left at the discretion of the investigators. PATIENTS CHARACTERISTICS: All of the 175 relapsed/refractory FL2000 pts were considered for the purpose of this analysis. Patients had a confirmed FL. Sixty-three pts experienced progression while on therapy (26 during induction phase and 37 during consolidation phase), while 112 progressed after completion of their first line treatment (follow-up period). At time of first progression, median age was 60 (range, 25– 75) y. 105 patients were initially randomized in Arm A and 70 in Arm B. Median time from diagnosis to progression for pts who experienced relapse/progression after completion of the first line treatment was 2.75 y. In all, 154 pts received salvage therapy at first relapse/progression: a cytarabine-based regimen in 24% of cases, an alkylating agent-based regimen in 23%, an anthracycline-based regimen in 22% and a fludarabine-based regimen in 16.5%. Fifty-three pts did not receive anti-CD20 (with or without chemotherapy) at that time, including 24 ps initially randomized in arm A. Finally, 42 pts could proceed to auto-SCT at first relapse. RESULTS: After salvage therapy, 80 pts reached CR/CRu and 23 reached PR (missing data, 20%). The median follow-up (calculated from time of first progression) is 30.8 m. The 3- and 5-year progression-free survival (PFS) estimates were 50% and 26%, respectively. The 3- and 5-year overall survival (OS) estimates were 72% and 52%, respectively. When taking into account the initial randomization, no differences in OS and PFS were observed between arm A and B. In univariate analysis, 5 parameters significantly influenced PFS and OS: younger age (p=0.035 and p=0.004; respectively), relapse/progression occurring during the follow-up period (p=0.001 and p=0.0004; respectively), low FLIPI score at diagnosis (p=0.015 and p=0.004; respectively), and actual performance of auto-SCT (p=0.0015 and p=0.001; respectively). Of note, an anti-CD20- containing therapy improved the PFS (p=0.005). In multivariate analysis, 3 parameters remained significant for PFS: period of relapse/progression (p=0.0001); an anti-CD20 containing therapy (p=0.03) and auto-SCT (p=0.002). 2 parameters remained significant for OS: period of relapse/progression (p=0.0001) and auto-SCT (p=0.0001). The 3-year OS for patients younger than 70 years who received ASCT was 92% compared to 59% for other patients (p=0.0001) CONCLUSION: These results suggest that Rituximab should be included in the salvage regimen for relapsed FL, even for those patients who previously received Rituximab. Furthermore, such pts may benefit from auto-SCT both in terms of PFS and OS. Therefore, a Rituximab-based chemotherapy regimen followed by auto-SCT is likely to be the standard of care for eligible relapsed/refractory FL patients.