TREATMENT OF HIGH-RISK ACUTE-LEUKEMIA WITH T-CELL-DEPLETED STEM-CELLSFROM RELATED DONORS WITH ONE FULLY MISMATCHED HLA HAPLOTYPE

Background In this study we tried to achieve successful transplantatio n in patients with acute leukemia with the use of hematopoietic stem c ells from donors who shared only one HLA haplotype with the recipient (a ''full-haplotype mismatch''). To prevent graft failure, large doses of T-cell-depleted hematopoietic stem cells were transplanted after a conditioning regimen of enhanced myeloablation and immunosuppression was administered to the recipient. Methods Forty-three patients with h igh-risk acute leukemia who were scheduled for transplantation receive d total-body irradiation, thiotepa, fludarabine, and antithymocyte glo bulin. The graft consisted of peripheral-blood progenitor cells that h ad been mobilized in the donor with recombinant granulocyte colony-sti mulating factor and also, in 28 cases, bone marrow. Bone marrow from t he donor was depleted of T lymphocytes by processing with soybean aggl utinin and E-rosetting. T-cell depletion of peripheral-blood mononucle ar cells was achieved by E-rosetting followed by positive selection of CD34+ cells. No post-transplantation prophylaxis against graft-versus -host disease (GVHD) was administered, Results In all the patients, fu ll donor-type engraftment was achieved. In none of the patients who co uld be evaluated did acute or chronic GVHD develop. Regimen-related to xicity was minimal. Eleven of the 23 patients with acute lymphoblastic leukemia had a relapse, as did 2 of the 20 patients with acute myeloi d leukemia. Transplantation-related mortality was 40 percent. After a median follow-up of 18 months (range, 8 to 30), 12 of the 43 patients were alive and free of disease. All surviving patients had a good qual ity of life. Conclusions The main limitations of transplantation of bo ne marrow from donors who are matched with the recipient for only one HLA haplotype GVHD and graft failure - can be overcome. Since most pat ients have a relative with one haplotype mismatch, advances in this me thod will increase the availability of hematopoietic-cell transplantat ion as curative therapy for acute leukemia. (N Engl J Med 1998;339:118 6-93.) (C) 1998, Massachusetts Medical Society.