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Sasazuki et al. (Oct. 22 issue) (1) report increased survival at one year among patients who underwent transplantation of hematopoietic stem cells from unrelated donors that was associated with matching of HLA-A alleles. They do not report the effect of isolated HLA-A mismatches. Thus, the effect of HLA-A mismatches could be due to multiple mismatches of linked HLA-C, B, and DRB1 alleles.
Thomas H. Eiermann, M.D., Ph.D.
University Hospital Eppendorf
20246 Hamburg, Germany
References
1. Sasazuki
T, Juji T, Morishima Y, et al. Effect of matching of class I HLA alleles
on clinical outcome after transplantation of hematopoietic stem cells
from an unrelated donor. N Engl J Med 1998;339:1177-85.
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The October 22 issue contains important and well-reported studies by Sasazuki et al. and Aversa et al., (1) as well as an accompanying editorial by van Rood and Oudshoorn (2) that describe new and complex developments in the clinical application of allogeneic bone marrow transplantation. However, we want to remind these authors of the information already available from animal models of allogeneic bone marrow transplantation.
The conclusion reached by Sasazuki et al. that class I major-histocompatibility-complex (MHC) antigens are more important than class II MHC antigens in controlling graft-versus-host disease (GVHD) and host-versus-graft reactions was fully predicted by research in rhesus monkeys reported nearly 20 years ago. (3,4) These results were supported by clinical data (5) but were largely ignored by the bone marrow-transplantation community. Unfortunately, Sasazuki et al. did not provide information on the number of bone marrow cells and T lymphocytes infused; research in animals suggests that both variables influence acceptance of the graft and the incidence of GVHD. (6,7)
The article also lacks information on conditioning regimens and immunosuppressive treatment after transplantation. Even in the unlikely event that all patients were treated according to a single protocol, such information is essential for the evaluation of these important results.
The study by Aversa et al. confirms that rigorous depletion of T cells from donor bone marrow can prevent GVHD and that a high-dose conditioning regimen, large numbers of stem cells, or both can promote grafting even in the case of bad mismatches. (3,4) On these points the authors have relied on evidence from animal models. However, with respect to the choice of the conditioning regimen, the authors have ignored two important lessons from the laboratory. First, the interval between total-body irradiation and grafting was unnecessarily long, resulting in an extended period of leukopenia. Second, gastrointestinal decontamination should have been included to reduce mortality due to infection and to promote immunologic reconstitution. (4) Their results demonstrate that even when graft failure and GVHD are prevented, haploidentical grafts are still associated with a very high risk. We urgently recommend that further use of haploidentical donors for adult patients be postponed until the problem of impaired immunologic reconstitution is solved.
Dirk W. van Bekkum, M.D., Ph.D.
IntroGene
2301 CA Leiden, the
Netherlands
Huibert M. Vriesendorp, M.D., Ph.D.
6641 Westchester
Houston,
TX 77005
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