In Vivo T Cell Depletion with Low-Dose Rabbit Antithymocyte Globulin Results in Low Transplant-Related Mortality and Low Relapse Incidence Following Unrelated Hematopoietic Stem Cell Transplantation

Abstract

Stem cell transplantation from unrelated donors is associated with an increased risk of graft failure and graft-versus-host disease (GVHD). Addition of pretransplant antithymocyte globulin (ATG), although reducing the risk of graft rejection and GVHD, bears the risk of overimmunosuppression, resulting in an increased relapse rate and transplant-related mortality. Therefore, we evaluated in 21 consecutive patients receiving unrelated stem cell grafts from either HLA-matched (38%) or -mismatched (62%) donors whether low-dose rabbit ATG added to cyclosporin A and methotrexate at a total dose of 3.5 mg/kg for HLA-identical and 5.0 mg/kg for HLA-mismatched transplants given in two divided doses on days -2 and -1 provides sufficient immunosuppression for prevention of GVHD and graft rejection but is associated with an acceptable risk of relapse and transplant-related mortality. Stable leukocyte engraftment was achieved in all patients (100%). Overall survival after a median follow-up of 26 (median, range 14–42) months was 56 ± 26% (95% confidence interval, CI) and the overall relapse rate at 3 years was 24 ± 21%. Three-year survival for standard-risk patients, i.e., chronic myeloid leukemia (CML) in first chronic phase or acute leukemia in first complete remission, was 87% ± 13% versus 40% ± 31% for patients with more advanced disease. The incidence of acute GVHD II–IV° was 55 ± 22%; that of severe acute GVHD III–IV° was 21 ± 19%. Chronic GVHD was observed in 5/17 (29%) patients surviving more than 100 days post stem cell transplantation. Transplant-related mortality was 16 ± 15% (95% CI) at day + 100 and 25 ± 19% (95% CI) at 1 year after the transplant. The data presented show that pretransplant in vivo T cell depletion with low-dose rabbit ATG results in a low transplant-related mortality due to a low incidence of severe acute and chronic GVHD and a low relapse rate. To find out the optimal rabbit ATG dose in the unrelated stem cell transplantation setting, further dose-finding studies comparing high- and low-dose regimens are necessary.