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Female‐Versus‐Male Alloreactivity as a Model for Minor Histocompatibility Antigens in Hematopoietic Stem Cell Transplantation
Author(s) -
Stern M.,
Brand R.,
De Witte T.,
Sureda A.,
Rocha V.,
Passweg J.,
Baldomero H.,
Niederwieser D.,
Gratwohl A.
Publication year - 2008
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2008.02374.x
Subject(s) - minor histocompatibility antigen , medicine , histocompatibility , transplantation , immunology , hematopoietic stem cell transplantation , human leukocyte antigen , graft versus host disease , stem cell , disease , haematopoiesis , antigen , major histocompatibility complex , biology , genetics
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.