Female-Versus-Male Alloreactivity as a Model for Minor Histocompatibility Antigens in Hematopoietic Stem Cell Transplantation

Authors: Stern, M.; Brand, R.¹; de Witte, T.²; Sureda, A.³; Rocha, V.⁴; Passweg, J.⁵; Baldomero, H.⁶; Niederwieser, D.⁷; Gratwohl, A.⁶

Source: American Journal of Transplantation, Volume 8, Number 10, October 2008 , pp. 2149-2157(9)

Publisher: Wiley-Blackwell

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Abstract:

H-Y encoded gene products were the first to be recognized as clinically relevant minor histocompatibility antigens. Compared to other gender combinations, female donor/male recipient (FDMR) transplants are associated with increased graft-versus-host disease (GvHD), increased transplant-related mortality (TRM) and reduced risk of relapse. Still, their relative impact on transplant outcome remains controversial. We analyzed donor/recipient sex combination in 53 988 patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) between 1980 and 2005. We found a strong increase in chronic GvHD and late TRM and decreased survival in FDMR transplants irrespective of underlying disease. Conversely, FDMR patients had lower relapse rates. The negative effect on survival decreased with advancing disease stage as relapse protection became more important. Effects of H-Y alloreactivity were most pronounced in patients transplanted from HLA-matched donors and in those receiving transplants from an adult donor. Adjustment for acute and chronic GvHD only partially corrected the effects of H-Y alloreactivity. Analysis of the FDMR proportion over time indicated that the frequency of this gender combination has declined in unrelated transplants over the last 10 years. These data define the role of H-Y mismatching in allogeneic HSCT and support the current practice of avoiding female donors for male patients, if possible.

Keywords: Gender; hematopoietic stem cell transplantation; leukemia; minor histocompatibility antigens

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1600-6143.2008.02374.x

Affiliations: 1: Department of Medical Statistics, University of Leiden, The Netherlands 2: Department of Hematology, Radboud University Medical Centre, Nijmegen, The Netherlands 3: Clinical Hematology Division, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain 4: Department of Hematology, Assistance Publique des Hôpitaux de Paris (APHP), Université de Paris, France 5: Division of Hematology, University Hospital, Geneva, Switzerland 6: Department of Hematology, University Hospital, Basel, Switzerland 7: Division of Haematology & Oncology, University Hospital, Leipzig, Germany

Publication date: 2008-10-01

Female-Versus-Male Alloreactivity as a Model for Minor Histocompatibility Antigens in Hematopoietic Stem Cell Transplantation

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