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

• Verfasst von: Radujković, Aleksandar [VerfasserIn]
• Verfasst von: Rachakonda, P. Sivaramakrishna [VerfasserIn]
• Verfasst von: Müller-Tidow, Carsten [VerfasserIn]
• Verfasst von: Dreger, Peter [VerfasserIn]
• Verfasst von: Luft, Thomas [VerfasserIn]
• Titel: Asymmetric dimethylarginine serum levels are associated with early mortality after allogeneic stem cell transplantation
• Verf.angabe: Aleksandar Radujkovic, Hao Dai, Lambros Kordelas, Dietrich Beelen, Sivaramakrishna P. Rachakonda, Carsten Müller-Tidow, Rajiv Kumar, Peter Dreger and Thomas Luft
• E-Jahr: 2019
• Jahr: [April 2019]
• Umfang: 8 S.
• Illustrationen: Diagramme
• Fussnoten: Gesehen am 22.05.2019
• Titel Quelle: Enthalten in: Haematologica
• Ort Quelle: Pavia : Ferrata Storti Foundation, 2014
• Jahr Quelle: 2019
• Band/Heft Quelle: 104(2019), 4, Seite 827-834
• ISSN Quelle: 1592-8721
• DOI: doi:10.3324/haematol.2018.202267
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1666081329

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.