Autologous Stem Cell Transplantation (ASCT) Versus Standard Treatments for CLL Patients: First Interim Analysis of a Prospective Randomized Study from the French Cooperative Study Group on CLL.

Patients with stage B or C CLL, under 66 years, previously untreated are included in this trial. They are scheduled to receive 3 monthly courses of mini-CHOP (3mC) followed by 3 monthly courses of Fludarabine (3F) before evaluation of the response. Patients in complete response (NCI) undergo stem cells mobilisation with G-CSF alone, then are randomized between ASCT and observation. Patients not in CR receive 1 or 2 courses of DHAP for mobilisation of stem cells and are randomized between ASCT or 3 monthly courses of Fludarabine/Cytoxan (F/C). The primary endpoint in this study is EFS at 3 years. This first interim analysis was planed after the randomisation of the first 100 patients (6 October 2004). At that time, 142 patients have been included. Among them, 16 have not completed yet the full treatment before randomization; 26 were not randomized because of early death (9), erroneous inclusion (3), autoimmune hemolytic anemia (2), cytopenia (2), investigator’s or patient’s decision (10). From these 26 patients, 14 were nevertheless assessable for response after they received 3mC+3F (1 CR, 4 PR, 2 SD, 7 PD), 6 failed and 6 were not evaluable for response. For each included patient, cytology, flow cytometry, cyclin D1 expression and biological pronostic factors (cytogenetics, IgVH, mutational status, ZAP70 expression) were centrally reviewed. At baseline, 110 patients were in Binet stage B and 32 in Binet stage C. Median age at inclusion was 55 years (min: 31, max: 65). After the six monthly courses (3mC+3F), overall response (CR + PR) was 82.5% (99/120 patients); 49 patients were in CR (41%) from which 48 were randomized between observation and ASCT. 52 patients, not in CR, (46 PR, 5 SD, 1 PD) were randomized between ASCT and F/C. After randomisation, 9 patients died from refractory disease (6), pneumonia (3), neither after ABMT. Two patients had prolonged pancytopenia: one after ASCT who was further allografted and one after F/C. Four patients experienced a Richter syndrome, 3 before ASCT, 1 in the observation arm. Two patients developed hemolytic anemia (one after DHAP, one after the first course of F/C). One patient had hepatitis B virus reactivation 6 months after ASCT. This study is ongoing until randomization of 208 patients. These preliminary results show that in advanced stage CLL (B and C Binet stages) the 3mC+3F regimen displays a very good response rate, which compares favorably with the best published ones. The study of the impact of pronostic biological parameters on response rate is on progress and will be presented at the meeting.