Non Myeloablative Allogeneic Related Transplant in Patients with Aggressive B Cell Lymphoma: Results of Two Multicenter Spanish Trials. The GELTAMO Group.

Although autologous transplant is the election in poor prognosis patients with Non Hodgkin agressive histologies, some patients relapse, for others collection of progenitor cells is not possible and in some categories as Mantle Cell Lymphoma results after autologous transplant are dismal. From 1999, three prospective multicenter trials with non-myeloablative allogeneic transplant in hematological malignancies have been performed in Spain. Up to now, 36 patients have been registered in these trials. From them,28 (58%)had aDBLCL,1 (3%) a transformed MZL,1 (3%) a BL and 14 (37%) a MCL. The conditioning regimen consisted of fludarabine 30 mg /m² intravenously (IV) on days −8 to −4 followed by melphalan 70–140 mg/m² IV on days −3 and−2. The last 25 patients enrolled in the latest trial received rituximab 375mg/ m^2;on days −8, −1,+8 and +15 as part of conditioning; filgrastim stimulated peripheral blood stem cells were infused on day 0. GVHD prophylaxis consisted of cyclosporine A (CsA) from day −7 plus short-course methotrexate (MTX) (10mg/m2, days +1, +3, +6), followed by folinic acid rescue. Median age was 51 years (range 27–68);at transplant 5 (13%) of the patients were in CR1, 4 (11%) in a later CR and 29 (76%) had active disease 18 (47%) had sensitive disease and 11 (29%) resistant disease. Days to reach more than 500x 10⁹ granulocytes and more than 20000x10⁹ platelets were +14 (range 10–93) and +12(range 8–18). At a median time of 25 days (range 19–97), 19 patients (50%) developed acute GVHD (13 patients (34%) grade II–IV). At a median time of 107 days(80–267), 68% out of 19 patients at risk developed cGVH being extensive in 11 (39%)Disease was evaluated at day +100 and at that moment 23 patients(65%) were in CR (including 4 / 8 patients transplanted on PGR), 4% in PR and 23% have died due to NRM(Non relapse mortality). With a median follow up of 31 months (range: 6–67 months), 19 patients (50%) are alive, 17 disease free and 19(50%) have died, 10(26%) due to NRM and 8 (21%) due to progression with a proyected NRM at 1 year of 22%. OS and EFS at 5 years of of 43 and 36% respectively. None of the variables analysed influenced on NRM. Regarding efficacy of transplant in different histologies, OS and DFS for MCL were 71% and for BDLCL, 31% and 20% respectively. In this preliminary analysis results in MCL are quite good however for patients with DLBCL should be improved. severe toxicity is still present and to date it should be performed only in the setting of well designed clinical trials.