Female donors influence transplant-related mortality and relapse incidence in male recipients of sibling blood and marrow transplants.
BACKGROUND
The male H-Y antigen is recognised as a minor histocompatibility antigen with debatable relevance and has not been substantiated thus far in clinical solid organ transplantation. An increase in transplant-related mortality in male recipients of female stem cells has been recognised and attributed to graft vs host effect against H-Y; in contrast, decreased incidence of relapse, a graft vs leukaemia effect has not yet been described.


METHODS
To detect potentially small but significant differences, we performed an analysis in a highly homogeneous group. We have analysed 782 patients, 438 males and 344 females, who were transplanted from HLA-identical female donors for CML in 1st chronic phase between 1989 and 1997. The risk of transplant related mortality (TRM) and relapse incidence (RI) were compared for male and female recipients over three successive time periods, zero to three months, three months to two years and two to five years post-transplant. Both groups were comparable for known risk factors prior to transplant.


RESULTS
The cumulative risk of TRM at five years was significantly higher in males (42%, s.e.=3.6) than in females (27%, s.e.=2.8; P=0.02) with no overall effect on risk of relapse. Within the three specified time intervals post-transplantation, the number of events of TRM and RI in the two groups of recipients diverged over time. There was no difference within the first time interval (zero to three months) for both events. TRM was higher in male recipients as manifested from three months onwards over the whole observation period of five years (P=0.02). Risk of relapse was significantly reduced in male patients; this difference became manifest only beyond two years (P=0.01).


CONCLUSIONS
These data confirm the importance of male gender for both, TRM and RI: male recipients of female blood or marrow grafts are at risk of enhanced procedure related mortality, eg GvHD, but benefit from reduced incidence of disease recurrence, hence a GvL effect. GvL in this setting needs more time than GvHD. These data give indirect but convincing evidence for a clinical relevance of H-Y as a minor histocompatibility antigen in humans.
Gratwohl
A
A
Division of Hematology, Department of Internal Medicine, Kantonsspital Basel, Switzerland. hematology@uhbs.ch
Hermans
J
J
Niederwieser
D
D
van Biezen
A
A
van Houwelingen
H C
HC
Apperley
J
J
D000328:Adult; D001773:Blood Cells / Q000637:transplantation; D016026:Bone Marrow Transplantation; D005260:Female; D020544:Graft vs Leukemia Effect; D006182:H-Y Antigen / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006648:Histocompatibility; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000628:therapy; D008297:Male; D009679:Nuclear Family; D012008:Recurrence; D012189:Retrospective Studies; D012737:Sex Factors; D016019:Survival Analysis; D014019:Tissue Donors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous / Q000276:immunology / Q000401:mortality
D006182:H-Y Antigen