Page 294 - Haematologica May 2020

Ferrata Storti Foundation
Haematologica 2020 Volume 105(5):1454-1464
Stem Cell Transplantation
Pre-transplant testosterone and outcome of men after allogeneic stem cell transplantation
Aleksandar Radujkovic,1 Lambros Kordelas,2 Julia Krzykalla,3 Axel Benner,3 David Schult,1 Joshua Majer-Lauterbach,1 Dietrich W. Beelen,2
Carsten Müller-Tidow,1 Christian Kasperk,4 Peter Dreger1 and Thomas Luft1
1Department of Internal Medicine V, University of Heidelberg, Heidelberg; 2Department of Bone Marrow Transplantation, University Hospital, Essen; 3Division of Biostatistics, German Cancer Research Center, Heidelberg and 4Department of Internal Medicine I, University of Heidelberg, Heidelberg, Germany
ABSTRACT
Testosterone is an important determinant of endothelial function and vascular health in men. As both factors play a role in mortality after allogeneic stem cell transplantation (alloSCT), we retrospectively evaluated the impact of pre-transplant testosterone levels on outcome in male patients undergoing alloSCT. In the discovery cohort (n=346), an impact on outcome was observed only in the subgroup of patients allograft- ed for acute myeloid leukemia (AML) (n=176, hereafter termed 'training cohort'). In the training cohort, lower pre-transplant testosterone levels were significantly associated with shorter overall survival (OS) [hazard ratio (HR) for a decrease of 100 ng/dL: 1.11, P=0.045]. This was based on a higher hazard of non-relapse mortality (NRM) (cause-specific HR: 1.25, P=0.013), but not relapse (cause-specific HR: 1.06, P=0.277) in the multivari- able models. These findings were replicated in a confirmation cohort of 168 male patients allografted for AML in a different center (OS, HR: 1.15, P=0.012 and NRM, cause-specific HR: 1.23; P=0.008). Next, an optimized cut-off point for pre-transplant testosterone was derived from the training set and evaluated in the confirmation cohort. In multivariable models, low pre-transplant testosterone status (<250 ng/dL) was associated with worse OS (hazard ratio 1.95, P=0.021) and increased NRM (cause-specific HR 2.68, P=0.011) but not with relapse (cause-specific HR: 1.28, P=0.551). Our findings may provide a rationale for prospective studies on testosterone/androgen assessment and supplementation in male patients undergoing alloSCT for AML.
Introduction
Allogeneic stem cell transplantation (alloSCT) is an effective therapy for many hematologic malignancies, but is still hampered by substantial procedure-related mortality and morbidity. Today, there is growing recognition that endothelial dys- function is implicated in the pathogenesis of a variety of potentially fatal early and late complications of alloSCT, such as transplant-associated thrombotic microan- giopathy, cardiovascular disorders, and graft-versus-host disease (GvHD).1,2
In particular, therapy refractory GvHD is a substantial determinant of non-relapse mortality (NRM) after alloSCT, and “endothelial vulnerability” was proposed as a hypothesis to explain why some patients with acute GvHD fail to respond to esca- lating immunosuppressive therapy and ultimately succumb to GvHD and/or treat- ment related complications.3-6
In male individuals, low serum testosterone has been linked to endothelial dys- function and all-cause and cardiovascular disease-related mortality in various non- transplant settings.7-9 This is of particular importance as alloSCT is increasingly used in elderly populations characterized by declining sex hormone activity. Notably, with regard to hematologic malignancies, testosterone and androgens have also been used as adjunct in the treatment of acute myeloid leukemia (AML).10-12
Based on these considerations, we sought to evaluate the impact of pre-trans- plant testosterone levels on outcome in male patients undergoing alloSCT.
Correspondence:
THOMAS LUFT
thomas.luft@med.uni-heidelberg.de
Received: February 23, 2019. Accepted: July 10, 2019. Pre-published: July 11, 2019.
doi:10.3324/haematol.2019.220293
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/5/1454
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