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CORRESPONDENCE Recipient disparity for the HA-1 minor histocompatibility
antigen has been associated with acute graft-versus-host disease (GVHD)
after marrow transplantation from an HLA-identical
sibling.1 We have also shown a trend toward higher risk of
grades II to IV acute GVHD in recipients mismatched for HA-1 among a
selected HLA-A2-positive population (P = .08), but the
odds ratio (2.1) was lower than the value (5.4) reported by Goulmy et
al.1,2 In our earlier study, all patients received
methotrexate and cyclosporine for GVHD prophylaxis and had either grade
0 or grades II to IV acute GVHD. The analysis excluded patients with
grade I GVHD, those with renal failure requiring dialysis, and those
who died within 80 days after the transplantation without having GVHD. These selection criteria were designed to provide high sensitivity for
detecting an association between HA-1 disparity and the development of
acute GVHD but did not allow an evaluation of other end points, such as
chronic GVHD, leukemia relapse, and transplant-related mortality and survival. We have extended our earlier results in order to evaluate these
additional end points. DNA samples from both patients and donors
(including the initial 237 pairs) were available for 613 HLA-A2-positive patients who received marrow from an HLA-identical sibling at the Fred Hutchinson Cancer Research Center (Seattle, WA)
from 1981 to 1998. The availability of DNA samples and the use of
methotrexate and cyclosporine for GVHD prophylaxis were the only
inclusion criteria. Genotyping of HA-1 and sequencing of HLA-A2 were
performed as previously described.2 HA-1 disparity, defined as the presence of HA-1H in
the recipient but not in the donor, was detected in 80 (13%) of the
613 donor/recipient pairs. The HLA-A2 sequence was determined among the
80 patients mismatched for HA-1. Eight patients who did not have
HLA-A*0201 were excluded from further analysis because the presentation
of HA-1 is HLA-A*0201-restricted.3 In a multivariable logistic regression analysis, HA-1 disparity showed no statistically significant association with a higher incidence of acute or chronic GVHD, a lower risk of leukemia relapse, a higher risk of nonrelapse mortality, or any increase or decrease in survival (Table
1). The low frequency of HA-1 disparity
makes it very difficult to demonstrate statistically significant
associations with outcome after hematopoietic stem cell
transplantation. Our current results do not exclude the possibility
that HA-1 disparity is associated with an increased risk of GVHD but
the odds ratio for any such association is likely to be less than 2.6. Similarly, our current results do not exclude the possibility that HA-1
disparity is associated with a reduced risk of recurrent malignancy but
the odds ratio for any such association is likely to be greater than 0.3. A very large multicenter study would be needed in order to have
adequate statistical power to detect associations of this magnitude.
Ming-Tseh Lin, Ted Gooley, John A. Hansen, Li-Hui Tseng, Emily G. Martin, Kentner Singleton, Anajane G. Smith, Eric Mickelson, Effie W. Petersdorf, and Paul J. Martin Supported in part by Grants AI33484, CA15704, CA18029 from the National Institutes of Health, Bethesda, MD References
1.
Goulmy E, Schipper R, Pool J, et al.
Mismatches of minor histocompatibility antigens between HLA-identical donors and recipients and the development of graft-versus-host disease after bone marrow transplantation.
N Engl J Med.
1996;334:281-285
2.
Tseng L-H, Lin M-T, Gooley T, et al.
Correlation between disparity for the minor histocompatibility antigen HA-1 and the development of acute graft-versus-host disease after allogeneic marrow transplantation.
Blood.
1999;94:2911-2914
3.
den Haan JM, Meadows LM, Wang W, et al.
The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymorphism.
Science.
1998;279:1054-1057   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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