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

No biomarker panel is 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 dehydrogena...

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Main Authors: Jiang, Sihe (Author) , Penack, Olaf (Author) , Terzer, Tobias (Author) , Schult, David (Author) , Majer-Lauterbach, Joshua (Author) , Radujković, Aleksandar (Author) , Blau, Igor W. (Author) , Bullinger, Lars (Author) , Müller-Tidow, Carsten (Author) , Dreger, Peter (Author) , Luft, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Haematologica
Year: 2020, Volume: 106, Issue: 2, Pages: 446-453
ISSN:1592-8721
DOI:10.3324/haematol.2019.238790
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3324/haematol.2019.238790
Verlag, lizenzpflichtig, Volltext: https://haematologica.org/article/view/9631
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Author Notes:Sihe Jiang, Olaf Penack, Tobias Terzer, David Schult, Joshua Majer-Lauterbach, Aleksandar Radujkovic, Igor W. Blau, Lars Bullinger, Carsten Müller-Tidow, Peter Dreger and Thomas Luft
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Summary:No biomarker panel is 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 CIBMTR clinical risk score 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% (p<0.0001, Heidelberg, 2010-2015, n=359) 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.
Item Description:Pre-published: January 23, 2020
Gesehen am 08.04.2021
Physical Description:Online Resource
ISSN:1592-8721
DOI:10.3324/haematol.2019.238790

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