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S. Jiang et al.
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Figure 3. Univariable effect of Endothelial Activation and Stress Index (EASIX) assessed at the day of alloSCT (EASIX-d0) on overall survival (OS) and non-relapse mortality (NRM). Univariable effect of EASIX-d0 on OS in (A) the training cohort and (B) the validation cohort. Univariable association of EASIX-d0 with NRM in (C) the training cohort and (D) the validation cohort.
cohort (univariable analysis: OR per log2 increase 1.19, 95%CI: 0.87-1.54, P=0.2288) (Figure 4A) nor in the valida- tion cohort (univariable analysis: OR per log2 increase 1.07, 95%CI: 0.92-1.20, P=0.308) (Figure 4B).
Brier score based on observed SOS/VOD incidence in the training cohort (null model) is 0.0774 in the validation cohort. Inclusion of EASIX-d0 leads to a reduction in the quadratic prediction error (0.0735) of approximately 5%. In contrast, Brier score of the CIBMTR score model (0.0771) is similar to the Brier score of the null model.
In both cohorts, the CIBMTR score was not predictive of OS or NRM (univariable analysis, training cohort, OS: HR per log2 increase 1.08, 95%CI: 0.95-1.22, P=0.2264; NRM: CSHR per log2 increase 1.15, 95%CI: 1.00-1.33, P=0.0565; validation cohort, OS: HR per log2 increase 1.03, 95%CI: 0.97-1.09, P=0.4126; NRM: CSHR per log2 increase 0.95, 95%CI: 0.84-1.08, P=0.4648).
Effect of pravastatin/ursodeoxycholic acid on sinusoidal obstruction syndrome/veno-occlusive disease incidence
Patients undergoing alloSCT in Heidelberg after January 2010 received pravastatin and UDA as routine prophylaxis of endothelial complications after alloSCT. In this cohort of 359 consecutive patients transplanted in Heidelberg between January 2010 and December 2015, the SOS/VOD incidence was significantly lower than in the training and
validation cohorts treated without endothelial prophylax- is (1.7%, vs. 9.6% and 8.4%, P<0.0001) (Figure 5A). Next, we focused on the effect of pravastatin/UDA prophylaxis on SOS/VOD incidence, NRM and OS in a population at increased risk for SOS/VOD, defined by the highest EASIX-d0 quartile in each of the three cohorts. The patient cohort at increased risk that received pravastatin/UDA showed a significantly lower SOS/VOD incidence (Figure 5B), lower NRM (Figure 5C), and higher OS (Figure 5D) compared to the high-risk patient popula- tions in the training and validation cohorts.
Discussion
In this retrospective cohort analysis, EASIX-d0 was found to be an independent predictor of SOS/VOD risk, OS and NRM in adult patients receiving alloSCT. EASIX- d0 constitutes the first validated biomarker for defining a subpopulation of alloSCT recipients at high risk for SOS/VOD. It consists of routine laboratory parameters enabling easy implementation in any transplant center. EASIX-d0 seems to be a readily available tool for stratify- ing patients into high- and low-risk populations, which could be useful to improve clinical management of SOS/VOD, and for identifying patient subsets for clinical trials on SOS/VOD prophylaxis. Outside of clinical stud-
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haematologica | 2021; 106(2)