Format

Send to

Choose Destination
Haematologica. 2019 Apr;104(4):827-834. doi: 10.3324/haematol.2018.202267. Epub 2018 Dec 4.

Asymmetric dimethylarginine serum levels are associated with early mortality after allogeneic stem cell transplantation.

Author information

1
Department of Internal Medicine V, University Hospital Heidelberg.
2
Department of Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg.
3
Department of Bone Marrow Transplantation, University Hospital Essen, Germany.
4
Department of Internal Medicine V, University Hospital Heidelberg thomas.luft@med.uni-heidelberg.de.

Abstract

Increasing evidence suggests that endothelial cell distress is associated with mortality after allogeneic stem cell transplantation and acute graft-versus-host disease. Asymmetric dimethylarginine is an endogenous nitric oxide synthase inhibitor that induces endothelial cell dysfunction. We analyzed the impact of pre-transplant serum levels of asymmetric dimethylarginine on outcome after allogeneic stem cell transplantation. Since acute graft-versus-host disease and its treatment are major contributors to post-transplant mortality, the effect of asymmetric dimethylarginine on outcome measures was also assessed after onset of acute graft-versus-host disease. A total of 938 patients allografted at two centers between 2002 and 2013 were included in the retrospective study. In multivariable models, higher pre-transplant asymmetric dimethylarginine levels were significantly associated with an increased risk of non-relapse mortality (hazard ratio 1.43 per 1-log2 increase, P=0.005) but not with relapse (hazard ratio 1.21, P=0.109) within the first year after transplantation. This translated into worse overall survival (hazard ratio 1.45, P<0.0001) and shorter progression-free survival (hazard ratio 1.30, P=0.002) in the first year after transplantation. Higher pre-transplant asymmetric dimethylarginine levels were also associated with shorter overall survival (hazard ratio 1.46, P=0.001) and progression-free survival (hazard ratio 1.32, P=0.010) and higher non-relapse mortality (hazard ratio 1.36, P=0.042) within 1 year after the onset of acute graft-versus-host disease. Taken together, our data indicate an association between pre-transplant asymmetric dimethylarginine status and early non-relapse mortality in allografted patients, both overall and after the onset of acute graft-versus-host disease. These findings underline the relevance of endothelial dysfunction for transplant complications.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center