SUCCESSFUL ENGRAFTMENT OF T-CELL-DEPLETED HAPLOIDENTICAL 3-LOCI INCOMPATIBLE TRANSPLANTS IN LEUKEMIA PATIENTS BY ADDITION OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR-MOBILIZED PERIPHERAL-BLOOD PROGENITOR CELLS TO BONE-MARROW INOCULUM

Patients who undergo transplantation with haploidentical ''three-loci' ' mismatched T-cell-depleted bone marrow (BM) are at high risk for gra ft failure. To overcome the host-versus-graft barrier, we increased th e size of the graft inoculum, which has been shown to be a major facto r in controlling both immune rejection and stem cell competition in mu rine models. Seventeen patients (mean age, 23.2 years; range, 6 to 51 years) with end-stage chemoresistant leukemia were received transplant s of a combination of BM with recombinant human granulocyte colony-sti mulating factor-mobilized peripheral blood progenitor cells from HLA-h aploidentical ''three-loci'' incompatible family members. The average concentration of colony-forming unit-granulocyte-macrophage in the fin al inoculum was sevenfold to 10-fold greater than that found in BM alo ne. The sole graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion of the graft by the soybean agglutination and E-rose tting technique. The conditioning regimen included total body irradiat ion in a single fraction at a fast dose rate, antithymocyte globulin, cyclophosphamide and thiotepa to provide both immunosuppression and my eloablation. One patient rejected the graft and the other 16 had early and sustained full donor-type engraftment. One patient who received a much greater quantity of T lymphocytes than any other patient died fr om grade IV acute GVHD. There were no other cases of GVHD greater than or equal to grade II. Nine patients died from transplant-related toxi city, 2 relapsed, and 6 patients are alive and event-free at a median follow-up of 230 days (range, 100 to 485 days). Our results show that a highly immunosuppressive and myeloablative conditioning followed by transplantation of a large number of stem cells depleted of T lymphocy tes by soybean agglutination and E-rosetting technique has made transp lantation of three HLA-antigen disparate grafts possible, with only ra re cases of GVHD. (C) 1994 by The American Society of Hematology.