De. Speiser et al., HIGH-RESOLUTION HLA MATCHING ASSOCIATED WITH DECREASED MORTALITY AFTER UNRELATED BONE-MARROW TRANSPLANTATION, Blood, 87(10), 1996, pp. 4455-4462
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.