Contrasting the Long-Term Outcome of Reduced-Intensity Allogeneic Stem Cell Transplantation From Related Matched and Mismatched or Unrelated Matched Donor

Abstract 2029

Reduced-intensity conditioning (RIC) transplantation has been widely used in the treatment of hematological diseases. However, the comparison of long-term outcomes of RIC with HLA-matched, HLA–mismatched and unrelated donor is still lacking. Here, we reported the results of hematological patients treated at the China RIC Cooperative from the HLA-matched, HLA–mismatched and unrelated donor following to RIC. 514 patients with hematological diseases from the China RIC Cooperative Group were enrolled in this study, including 370 in HLA-matched group, 96 in HLA-mismatched group and 48 in unrelated group (table 1). The RIC conditioning regimen was based on fludarabine in combination with antilymphocyte globulin or busulfan or others. The graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A, mycophenolate mofetil and methotrexat. Results showed that 505 patients achieved stable donor chimerism. The incidence of II-IV aGVHD in the HLA-mismatched group was 42.7%, significantly higher than that in the HLA-matched group (21.4%) and the unrelated group (20.8%). The 100-day transplantation-related mortality was 30.2%, 14.5% and 4.2% in the three groups, respectively. The median follow-up time was 57 months (range,7 to 141 months). The overall relapse incidence was 14.8%, including 15.7% in the HLA-matched group, 14.6% in the HLA-mismatched group and 8.3% in the unrelated group. There was no significant difference in relapse incidences in the patients with AL-CR1 and CML-CP (16.4% and 11.2%), as well between the HLA-matched group (16.9% and 16.7%) and the unrelated group (11.1% and 8.8%). For the patients with advanced leukemia, a significantly lower relapse rate was found in the HLA-mismatched group in comparison with that in the HLA-matched group (18% vs 36.2%, p<0.05, Fig. 1).The Kaplan-Meier estimated DFS and OS at 6 years for all of the 514 patients were 58.6% and 61.9% respectively, and those at 11 years were 57.8% and 61.7% respectively. The DFS and OS at 6 years in the HLA-mismatched group was 35.4% and 38.5% respectively, lower than those at 11 years in the HLA-matched group (62.7% and 67.0%, p<0.01) and those at 6 years in the unrelated group (64.6% and 66.7%, p<0.01, Figure 2 A, B). The 11-year DFS for the patients with AL-CR1, CML-CP and MDS/SAA was 68.7%, 68.5% and 73.6% respectively in the HLA-matched group. The 6-year DFS for the patients with AL-CR1, CML-CP and MDS/SAA was 55.6%, 70.7% and 62% respectively in the unrelated group, and 37.5%, 62.5% and28.6% respectively in the HLA-mismatched group. Figure 2 C,D,E£© However, the 6-year DFS in the patients with advanced leukemia was 32.0% in the HLA-matched related group, similar to that in the HLA-mismatched group (31.9%, p£¾0.05, Fig. Figure 2 F). These results indicate that RIC transplantation had similar outcome in the HLA-matched group and unrelated group but better than that from the HLA-mismatched group in haematology diseases. However, for the advanced leukemia patients, the HLA-mismatched transplantation had much lower leukemia relapse rate than in the HLA-matched group.

Fig 1: The relapse rate of the patients with advanced leukemia in the HLA-mismatched group and the HLA-matched group.