BONE-MARROW TRANSPLANTATION FOR CHRONIC MYELOID-LEUKEMIA WITH VOLUNTEER UNRELATED DONORS USING EX-VIVO OR IN-VIVO T-CELL DEPLETION - MAJOR PROGNOSTIC IMPACT OF HLA CLASS-I IDENTITY BETWEEN DONOR AND RECIPIENT

Between August 1985 and July 1994, we performed 115 volunteer unrelate d donor (VUD) bone marrow transplants (BMT) for first chronic phase (n = 86) or advanced phase (n = 29) chronic myeloid leukemia (CML). Stan dard serologic HLA typing of potential donors and recipients was suppl emented with one-dimensional isoelectric focusing (IEF) for class I pr oteins, allogenotyping for DR and DO alleles using DNA restriction fra gment length polymorphism (RFLP) analysis, and the measurement of anti recipient major histocompatibility complex (MHC) cytotoxic T-lymphocyt e precursor cells in the donors' blood (CTLp assay), Recipients were c onditioned for transplantation with a combination of high-dose chemoth erapy and total body irradiation (n = 103) or high-dose chemotherapy a lone (n = 12), Twenty eight recipients received ex vivo T-cell-deplete d marrow, and 84 underwent some form of in vivo T-cell depletion. The probability of severe (grades III or IV) acute graft-versus-host disea se (aGVHD) was 24%, and that of extensive chronic graft-versus-host di sease (cGVHD), 38%. Proportional hazards regression analysis showed an association between low frequency CTLp and a reduced incidence of sev ere aGVHD (relative risk [RR], 0.28; P = .0035). The probability of re lapse at 3 years was 23%, with first chronic phase disease being indep endently associated with a lower risk of relapse (RR, 0.71; P = .01). The overall leukemia-free survival (LFS) at 3 years was 37%; the LFS f or the first chronic phase and advanced phase recipients was 41% and 2 6%, respectively, First chronic phase disease (RR, 0.56; P = .063) and the combination of recipient cytomegalovirus (CMV) seronegativity and an IEF-matched donor (RR, 0.48; P = .011) were both associated with i mproved LFS. The probabilities of survival and LFS for patients under 40 years of age transplanted in first chronic phase from an IEF-matche d donor were 73% and 50%, respectively. We conclude that VUD BMT is a reasonable option for patients with CML; when using ex vivo or in vivo T-cell depletion, optimal results are achieved in patients transplant ed in chronic phase with marrow from donors without demonstrable class I HLA mismatch and a low CTLp frequency. (C) 1995 by The American Soc iety of Hematology.