Transplantation of HLA-haploidentical T-cell-depleted marrow for leukemia: addition of cytosine arabinoside to the pretransplant conditioning prevents rejection.
A total of 41 patients with hematologic malignancies (other than acute leukemia in relapse) received allogeneic bone marrow transplants at the University of Wisconsin from 1 April 1980 through 31 March 1984. In an effort to minimize graft-versus-host disease, marrow was depleted of T-lymphocytes in vitro with monoclonal anti-T-cell antibody and complement prior to infusion for seven of 19 recipients of marrow from HLA-identical, MLC-nonreactive siblings, and for all 22 recipients of marrow from MLC-reactive HLA-haploidentical donors. The recipients of HLA-identical T-depleted marrow all showed excellent engraftment following standard pre-BMT conditioning with cyclophosphamide and total body irradiation. In contrast, five of five recipients of T-depleted haploidentical marrow failed to engraft following this same conditioning regimen. The addition of cytosine arabinoside to the pretransplant conditioning appeared to correct this problem, allowing engraftment in 14 of 17 subsequent patients. These clinical results, coupled with prior in vitro data, demonstrate the need to adequately suppress residual host-versus-graft immunity in order to prevent the rejection of T-cell-depleted HLA-haploidentical bone marrow.