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Ferrata Storti Foundation
Haematologica 2021 Volume 106(2):446-453
Complications in Hematology
Predicting sinusoidal obstruction syndrome after allogeneic stem cell transplantation with the EASIX biomarker panel
Sihe Jiang,1* Olaf Penack,1* Tobias Terzer,2 David Schult,3
Joshua Majer-Lauterbach,3 Aleksandar Radujkovic,3 Igor W. Blau,1
Lars Bullinger,1 Carsten Müller-Tidow,3 Peter Dreger3 and Thomas Luft3
1Charité Universitätsmedizin Berlin, Campus Virchow Clinic, Hematology, Oncology and Tumorimmunology, Berlin; 2Biostatistics, German Cancer Research Centre, Heidelberg and 3Medicine V, University Hospital Heidelberg, Heidelberg, Germany
*SJ and OP contributed equally as co-first authors.
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 con- trast, the CIBMTR score showed no statistically significant association with SOS/VOD incidence, and did not predict OS and NRM. In patients receiv- ing pravastatin/UDA, the cumulative incidence of SOS/VOD was signifi- cantly 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 validat- ed biomarker for defining a subpopulation of alloSCT recipients at high risk for SOS/VOD. Statin/UDA endothelial prophylaxis could constitute a pro- phylactic measure for patients at increased SOS/VOD risk.
Introduction
Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a potentially fatal complication after allogeneic stem cell transplantation (alloSCT).1-3 Clinical management of SOS/VOD remains challenging, since there are no standardized predictive tools4 and diagnostic criteria are not uniform.2,4-6 The reported incidences of SOS/VOD after alloSCT range from 5.3% to 13.7% and vary depending on conditioning regimens, type of transplant, diagnostic criteria, patient characteristics, and other factors.7-9
The pathophysiology of SOS/VOD is characterized by endothelial injury caused by the conditioning regimen as well as pre-transplant damage.1,2,10,11 The resulting post-sinusoidal portal hypertension leads to the clinical syndrome of SOS/VOD.2,5,6,11 In severe SOS/VOD, which is strongly associated with multi-organ failure, mortality remains high.2,8,11 Early detection or prediction of SOS/VOD could allow identification of patients who could benefit from prophylactic meas-
Correspondence:
OLAF PENACK
olaf.penack@charite.de
Received: September 26, 2019. Accepted: January 22, 2020. Pre-published: January 23, 2020.
https://doi.org/10.3324/haematol.2019.238790
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