We analyzed the relevance of HLA incompatibility to acute graft-versus-host disease,
relapse, and survival in 281 patients with hematologic neoplasms who underwent bone
marrow transplantation. Each patient received marrow from a family member who shared
one HLA haplotype with the patient but differed to a variable degree for the HLA-A,
-B, and -D antigens of the haplotype not shared; 29 were phenotypically identical,
119 were incompatible for one locus, 104 for two loci, and 29 for three loci. These
281 patients were compared with 967 patients who received marrow from siblings with
identical HLA genotypes. All patients were treated with cyclophosphamide and total-body
irradiation followed by the infusion of unmodified donor marrow cells. Occurrence
of severe acute graft-versus-host disease was evaluated in patients who achieved sustained
engraftment. In recipients of haploidentical grafts occurrence of severe acute graft-versus-host
disease was associated with (1) graft-versus-host disease prophylaxis containing the
combination of methotrexate plus cyclosporine versus standard methotrexate, relative
risk = 0.35; 95% confidence interval, 0.21-0.57, p less than 0.0001; and (2) the degree
of recipient HLA incompatibility, relative risk = 1.95 for each locus incompatible;
95% confidence interval, 1.52-2.50, p less than 0.0001; (3) patient age, relative
risk = 1.23 per decade; 95% confidence interval, 1.05-1.44, p = 0.0094. Acute graft-versus-host
disease was associated with lower leukemic relapse after transplant in patients with
acute lymphocytic leukemia, and chronic graft-versus-host disease was associated with
lower relapse after transplant for acute nonlymphocytic leukemia in relapse or chronic
myelogenous leukemia in blast crisis. After transplantation for acute nonlymphocytic
leukemia in remission, the rate of leukemic relapse was 22% in 61 recipients of "one-locus"
(A, B, or D)-incompatible grafts compared to 37% in 561 recipients of HLA-identical
sibling grafts. Survival was decreased as the degree of HLA disparity increased. Survival
of "one-locus"-incompatible transplant recipients, however, was equivalent to that
of HLA-identical sibling transplant recipients.