Correspondence

HLA Matching for Hematopoietic Stem-Cell Transplants

N Engl J Med 2002; 346:1251-1252April 18, 2002

Article

To the Editor:

Petersdorf et al. (Dec. 20 issue)1 suggest that for patients with chronic myelogenous leukemia for whom a donor with an HLA class I mismatch cannot be avoided, “the preferred . . . mismatch should be at a locus for which the recipient is heterozygous, thereby ensuring a concomitant recipient mismatch to counterbalance the donor mismatch.” However, 86 percent of the patients in their study with class I mismatches were also mismatched at class II loci. Therefore, the use of donors mismatched at class I loci would result in a significant number of grafts with disparities at both class I and class II loci, a condition that Petersdorf et al. have previously associated with a high risk of graft-versus-host disease.2 A strategy that reduces graft rejection at the expense of increased graft-versus-host disease may not be appropriate for most patients or those treated with different conditioning regimens. For example, graft rejection is probably much less common in patients who have been intensively treated before transplantation (unlike most patients with chronic-phase chronic myelogenous leukemia). The risk of rejection can also be partially overcome by the use of highly immunosuppressive drugs (e.g., fludarabine or pentostatin) in the conditioning program and by the use of blood stem cells.3 In fact, for patients who are homozygous at one of the class I loci, the intentional selection of donors with a mismatch at the locus for which the recipient is homozygous (a mismatch in the host-versus-graft direction only) might decrease the incidence of graft-versus-host disease without a significant risk of graft rejection.

Dennis L. Cooper, M.D.
Yale Cancer Center, New Haven, CT 06510
dennis.cooper@yale.edu

3 References

1. 1

   Petersdorf EW, Hansen JA, Martin PJ, et al. Major-histocompatibility complex class I alleles and antigens in hematopoietic-cell transplantation. N Engl J Med 2001;345:1794-1800
   Full Text | Web of Science | Medline

2. 2

   Petersdorf EW, Gooley TA, Anasetti C, et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. Blood 1998;92:3515-3520
   Web of Science | Medline

3. 3

   McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001;97:3390-3400
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: When an HLA-matched donor is not available, transplantation of hematopoietic stem cells from a partially mismatched donor may be lifesaving for some patients. We reported that in patients with chronic myeloid leukemia, transplants from donors with mismatches for a single HLA class I (A, B, or C) antigen are associated with an increased risk of graft failure when the recipient is homozygous, as opposed to heterozygous, at the mismatched locus. The data suggest that graft-versus-host reactivity in heterozygous recipients prevents rejection. Therefore, if only class I–mismatched donors are available for patients with chronic myelogenous leukemia, we have recommended selection of donors who are mismatched at a locus for which the recipient is heterozygous. As Cooper points out, this strategy could potentially increase the risk of graft-versus-host disease.

In previous studies, we found that the risk of graft-versus-host disease among patients with chronic myelogenous leukemia was not significantly affected by the presence of a single class I mismatch in the recipient. Likewise, the presence of class I disparities did not significantly increase the risk of graft-versus-host disease in recipients with mismatching of HLA-DRB1 or DQB1.1 Mortality was increased when the donor and recipient had mismatching at both a class I locus and HLA-DRB1 or DQB1. For patients with chronic myelogenous leukemia, we currently exclude potential donors from consideration when mismatching of this type is present. It is now known that most patients and unrelated donors have HLA-DPB1 mismatches, but more experience with transplants will be needed to measure the risks of graft-versus-host disease and mortality associated with mismatching for a class I locus and HLA-DPB1 in the absence of mismatching for HLA-DRB1 or DQB1. Information is not currently available to predict the risks and benefits of selecting a donor with mismatching for both HLA-DPB1 and a class I locus when the recipient is heterozygous rather than homozygous.

We agree that myeloablative regimens can overcome the risk of graft failure associated with class I disparity in immunocompromised recipients with disorders other than chronic myelogenous leukemia.2,3 The use of fludarabine may facilitate engraftment among HLA-matched siblings who have a high risk of graft rejection,4 but the efficacy of fludarabine in combination with low-intensity conditioning regimens has not yet been established for mismatched transplants.

Effie W. Petersdorf, M.D.
John A. Hansen, M.D.
Claudio Anasetti, M.D.
Fred Hutchinson Cancer Research Center, Seattle, WA 98109
epetersd@fhcrc.org

4 References

1. 1

   Petersdorf EW, Gooley TA, Anasetti C, et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. Blood 1998;92:3515-3520
   Web of Science | Medline

2. 2

   Aversa F, Tabilio A, Velardi A, et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998;339:1186-1193
   Full Text | Web of Science | Medline

3. 3

   Sierra J, Storer B, Hansen JA, et al. Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose. Blood 1997;89:4226-4235
   Web of Science | Medline

4. 4

   McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001;97:3390-3400
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Y. Sun, F. Kong, S. Ren, F. Yuan, F. Liang, N. Liu, L. Jin, Y. Xi. (2007) Severe acute graft-vs-host disease in a patient with acute monocytic leukemia having a recombination event between HLA-A/B loci from a multiple recombinant family. Tissue Antigens 70:6, 499-505
   CrossRef