HIGH-RESOLUTION HLA MATCHING ASSOCIATED WITH DECREASED MORTALITY AFTER UNRELATED BONE-MARROW TRANSPLANTATION

As compared with related HLA-identical sibling donors, bone marrow tra nsplantation (BMT) with phenotypically HLA ABDR-compatible unrelated d onors is associated with increased mortality. This may be due to hidde n HLA incompatibilities not detected by conventional typing. We have a nalyzed 44 unrelated patient-donor pairs who were matched for HLA-A. - B, and -DR by routine tissue typing. Our comprehensive HLA typing appr oach consisted of serology, cytotoxic T-cell precursor (CTLp) tests, T -cell cloning, oligotyping, and DNA sequencing. Using these techniques , we identified numerous HLA allele mismatches not detected by the pre viously applied routine typing. Twenty-four patient-donor pairs were h ighly matched and had a low CTLp frequency, whereas the remaining 20 p airs were allele-mismatched for HLA-A,-B,-C,-DR,-DQ antigens and/or ha d a positive result of the CTLp test. Patient and donor age, diagnosis , and treatment did not differ significantly between the matched and m ismatched transplants. The probability for severe acute graft-versus-h ost disease grades Ill-IV was 21% in the matched and 47% in the mismat ched patients (P = .0464). Transplant-related mortality was 21% and 57 % (P = .0072) and actuarial patient survival rates at 3 years were 61% and 13% (P = .0005). We conclude that both HLA class I and class II a llele mismatches between unrelated phenotypically ABDR-compatible pati ent-donor pairs are frequent and associated with increased incidence o f posttransplant complications. (C) 1996 by The American Society of He matology.