Haematologica, 11 July 2019
Testosterone is an important determinant of endothelial function and vascular health in men. As both factors play a role for mortality after allogeneic stem cell transplantation, we retrospectively evaluated the impact of pre-transplant testosterone levels on outcome in male patients undergoing allogeneic stem cell transplantation. In the discovery cohort (n=346), an impact on outcome was observed only in the subgroup of patients allografted for acute myeloid leukemia (n=176, hereafter termed training cohort). In the training cohort, lower pre-transplant testosterone levels were significantly associated with shorter overall survival (hazard ratio for a decrease of 100 ng/dL, 1.11, P=0.045). This was based on a higher hazard of non-relapse mortality (cause-specific hazard ratio 1.25, P=0.013), but not relapse (cause-specific hazard ratio 1.06, P=0.277) in the multivariable models. These findings were replicated in a confirmation cohort of 168 male patients allografted for acute myeloid leukemia in a different center (overall survival, hazard ratio 1.15, P=0.012 and non-relapse mortality, cause-specific hazard ratio 1.23, P=0.008). Next, an optimized cut-off point for pre-transplant testosterone was derived in the training set and evaluated in the confirmation cohort. In multivariable models, low pre-transplant testosterone status (〈250 ng/dL) was associated with worse overall survival (hazard ratio 1.95, P=0.021) and increased non-relapse mortality (cause-specific hazard ratio 2.68, P=0.011) but not with relapse (cause-specific hazard ratio 1.28, P=0.551). Our findings may provide a rationale for prospective studies on testosterone/androgen assessment and supplementation in male patients undergoing allogeneic stem cell transplantation for acute myeloid leukemia.
Graft-Versus-Host-Disease ; Stem Cell Transplantation ; Vascular Wall Biology and Platelet Adhesion ; Endothelial Cell Dysfunction ; Testosterone
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