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Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2911-2914
Correlation Between Disparity for the Minor Histocompatibility Antigen
HA-1 and the Development of Acute Graft-Versus-Host Disease After
Allogeneic Marrow Transplantation
Li-Hui Tseng,
Ming-Tseh Lin,
John A. Hansen,
Ted Gooley,
Ji Pei,
Anajane G. Smith,
Emily G. Martin,
Effie W. Petersdorf, and
Paul J. Martin
From the Division of Clinical Research, Fred Hutchinson Cancer
Research Center, Seattle, WA; the Department of Medical Genetics and
Oncology, National Taiwan University Hospital, Taipei, Taiwan; and the
Department of Internal Medicine, University of Washington,
Seattle, WA.
Results of a previous study suggested that recipient mismatching for
the minor histocompatibility antigen HA-1 is associated with acute
graft-versus-host disease (GVHD) after allogeneic marrow transplantation. In that study, most patients received either cyclosporine or methotrexate for GVHD prophylaxis, and a cytotoxic T-cell clone was used to test for HA-1 disparity. To facilitate large-scale testing, we developed a method that uses genomic DNA to
identify HA-1 alleles. A retrospective study was conducted to correlate
HA-1 disparity and the occurrence of acute GVHD in 237 HLA-A2-positive
white patients who had received a marrow or peripheral blood stem cell
transplant from an HLA-identical sibling. All patients received both
methotrexate and cyclosporine for GVHD prophylaxis. The presence of
HLA-A*0201 was confirmed in 34 of the 36 HA-1 disparate pairs by
sequencing the HLA-A locus. Grades II-IV GVHD occurred in 22 (64.7%)
of these 34 patients, compared with 86 (42.8%) of the 201 patients
without HA-1 disparity (odds ratio, 2.45; 95% confidence interval
[CI], 1.15 to 5.23; P = .02). Recipient HA-1 disparity
showed a trend for association with acute GVHD (odds ratio, 2.1; 95%
CI, 0.91 to 4.68; P = .08) when a multivariable logistic
regression model was used to include additional risk factors. These
data are consistent with results of the previous study, suggesting an
association between HA-1 disparity and risk of acute GVHD, but the
strength of this association may be lower in patients who received both
methotrexate and cyclosporine than in those who received methotrexate
or cyclosporine alone.

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