Comparison of Outcomes After Unrelated Cord Blood Transplantation and Matched Unrelated Donor RIC Transplantation for Lymphoid Malignancies - A Eurocord-Netcord Group/ Lymphoma Working Party and Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation Study.

Abstract 663

We have recently reported encouraging results after unrelated cord blood (UCBT) for patients with lymphoid malignancies (Rodrigues et al, 2009). Progression free survival (PFS) was improved in patients with chemosensitive disease, who have received a higher CD34 cell dose, and low-dose TBI in the preparative regimen. However, whether outcomes after reduced intensity conditioning (RIC) UCBT are comparable to outcomes after RIC-MUD for lymphoid malignancies remains to be defined. We studied 359 adult patients with lymphoma or chronic lymphocytic leukemia (CLL) who received an UCBT (n=75) or a MUD (n=284) after a RIC regimen between January 2000 and December 2006, and registered in the EBMT and/or the Eurocord databases were analyzed. In the MUD group, we included only patients receiving peripheral blood stem cells and with a 6/6 or a 8/8 match. Patients from 111 centers were included: UCBTs were performed in 28 centers and MUD transplants in 98 centers. Only 15 centers performed both types of transplant. One hundred sixty eight patients had a non-Hodgkin lymphoma (NHL), 108 had Hodgkin's lymphoma (HL), and 83 had CLL. In the UCBT group, patients were slightly younger (median age 44 vs. 48 in the MUD group, P=0.05), aggressive histologies and HL were more frequent (P=0.04), and more patients underwent the transplant in refractory or chemoresistant disease (P<0.001). There were also differences in the conditioning regimen: low-dose TBI was more often used in the UCBT group than in the MUD group (75% vs. 30%, respectively, P=0.002), while T-cell depletion with ATG/ALG (23% vs. 41%, p<0.001) or alemtuzumab (0% vs. 34%, p<0,001) was more often used in the MUD group. In the UCBT group, 31 patients (41%) received a double UCBT and, based on antigen-level HLA-A and B and allele-level HLA-DRB1 typing, at least one cord blood unit had 2 mismatches with the patient in 75% of cases. Median follow-up time of surviving patients was 28 months (32 months in the MUD group and 24 months in the UCBT group). The cumulative incidence (CI) of engraftment at day 60 was 85% in the UCBT group and 98% in the MUD group (P<0.001). At 100 days, CI of grade II-IV acute graft-versus-host disease (GVHD) was not statistically different between UCBT and MUD recipients (33% vs. 31%, P= not significant–NS). At 2 years, CI of chronic GVHD was 48% after MUD as compared to 37% after UCBT, (P=0.05). Non-adjusted 2 years CI of NRM was 28% after UCBT and 30% after MUD, (P=NS). There was also no difference in 2-year relapse or progression after UCB or MUDT (38% vs. 35%, P=NS). Two-year progression-free survival (PFS) was 34% after UCBT and 34% after MUD (P=NS) and overall survival was 44% and 47%, respectively (P=NS). In a multivariate analysis, after statistical adjustments for the differences between the 2 groups, NRM, relapse or progression, PFS and OS were not statistically different between UCBT and MUD. In conclusion, engraftment rate and incidence of chronic GVHD were lower after RIC-UCBT than after RIC-MUD but final outcomes were not different between the two groups. Therefore, UCBT may be considered as a valuable alternative for patients with advanced lymphoma and CLL, lacking an HLA-matched unrelated donor.