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Association of HLA-C disparity with graft failure after marrow
transplantation from unrelated donors
EW Petersdorf, GM Longton, C Anasetti, EM Mickelson, SK McKinney, AG Smith, PJ Martin and JA Hansen
Division of Clinical Research, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104, USA.
Disparity for HLA-A or HLA-B antigens increases the risk of marrow graft
rejection, but the relevance of HLA-C is unknown because typing methods
have not been sufficiently accurate for clinical use. We designed a matched
case-control study and employed DNA sequencing methods to evaluate the role
of HLA-C disparity in 21 patients who experienced graft failure (cases)
following transplantation with unmanipulated marrow from either HLA-A, B
serologically matched, DRB1 matched (n = 14) or single locus mismatched (n
= 7) unrelated donors. For each case, two patients who successfully
engrafted were selected as controls based on similarity for factors known
or suspected to influence engraftment. The estimated odds ratio (OR) of
graft failure for an HLA-C mismatch relative to match (univariable model)
was 5.2 (95% CI, 1.4, 19; P = .01). Serologically undetectable HLA-A or
HLA-B allele disparity was also associated with graft failure. The
association between HLA-C disparity and graft failure remained significant
even after accounting for the contribution of HLA-A and/or HLA-B allele
disparity (OR 4.0; 95% CI, 1.1, 15; likelihood ratio test P = .03). These
results show that HLA-C functions as a transplantation antigen and that
HLA-A and HLA-B allele mismatches are biologically important.
Molecular-based methods for pretransplant assessment of class I
compatibility should be implemented for the selection of unrelated marrow
donors.
Volume 89,
Issue 5,
pp. 1818-1823,
03/01/1997
Copyright © 1997 by The American Society of Hematology
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