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Predicting sinusoidal obstruction syndrome after allogeneic stem cell transplantation with the EASIX biomarker panel

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Item Type:Article
Title:Predicting sinusoidal obstruction syndrome after allogeneic stem cell transplantation with the EASIX biomarker panel
Creators Name:Jiang, S. and Penack, O. and Terzer, T. and Schult, D. and Majer-Lauterbach, J. and Radujkovic, A. and Blau, I.W. and Bullinger, L. and Müller-Tidow, C. and Dreger, P. and Luft, T.
Abstract:No biomarker panel has been established for prediction of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), a major complication of allogeneic stem cell transplantation (alloSCT). We compared the potential of the Endothelial Activation and Stress Index (EASIX), based on lactate dehydrogenase, creatinine, and thrombocytes, with that of the SOS/VOD clinical risk score of the Center for International Blood and Marrow Transplant Research (CIBMTR) to predict SOS/VOD in two independent cohorts. In a third cohort, we studied the impact of endothelium-active prophylaxis with pravastatin and ursodeoxycholic acid (UDA) on SOS/VOD risk. The cumulative incidence of SOS/VOD within 28 days after alloSCT in the training cohort (Berlin, 2013-2015, n=446) and in the validation cohort (Heidelberg, 2002-2009, n=380) was 9.6% and 8.4%, respectively. In both cohorts, EASIX assessed at the day of alloSCT (EASIX-d0) was significantly associated with SOS/VOD incidence (P<0.0001), overall survival (OS), and non-relapse mortality (NRM). In contrast, the CIBMTR score showed no statistically significant association with SOS/VOD incidence, and did not predict OS and NRM. In patients receiving pravastatin/UDA, the cumulative incidence of SOS/VOD was significantly lower at 1.7% (Heidelberg, 2010-2015, n=359, P<0.0001) than in the two cohorts not receiving pravastatin/UDA. The protective effect was most pronounced in patients with high EASIX-d0. The cumulative SOS/VOD incidence in the highest EASIX-d0 quartiles were 18.1% and 16.8% in both cohorts without endothelial prophylaxis as compared to 2.2% in patients with pravastatin/UDA prophylaxis (P<0.0001). EASIX-d0 is the first validated biomarker for defining a subpopulation of alloSCT recipients at high risk for SOS/VOD. Statin/UDA endothelial prophylaxis could constitute a prophylactic measure for patients at increased SOS/VOD risk.
Keywords:Biomarkers, Endothelium, Hematopoietic Stem Cell Transplantation, Hepatic Veno-Occlusive Disease, Risk Factors
Publisher:Ferrata Storti Foundation
Page Range:446-453
Date:February 2020
Official Publication:https://doi.org/10.3324/haematol.2019.238790
PubMed:View item in PubMed

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