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000182099 0247_ $$2doi$$a10.1111/eci.13883
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000182099 0247_ $$2ISSN$$a0014-2972
000182099 0247_ $$2ISSN$$a0960-135X
000182099 0247_ $$2ISSN$$a1365-2362
000182099 037__ $$aDKFZ-2022-02417
000182099 041__ $$aEnglish
000182099 082__ $$a610
000182099 1001_ $$aPabst, Caroline$$b0
000182099 245__ $$aStatin-based endothelial prophylaxis and outcome after allogeneic stem cell transplantation.
000182099 260__ $$aOxford [u.a.]$$bWiley-Blackwell$$c2023
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000182099 500__ $$a2023 Feb;53(2):e13883
000182099 520__ $$aAllogeneic haematopoietic stem cell transplantation (alloSCT) often remains the only curative therapy for hematologic malignancies. Although the management of transplant-associated adverse events considerably improved over the last decades, nonrelapse mortality (NRM) remains a challenge, and endothelial dysfunction was identified as a major contributor to NRM.Statin-based endothelial prophylaxis (SEP) has been implemented in the standard of care in our transplant centre to reduce NRM caused by endothelial injury. Here, we retrospectively analysed the impact of SEP on clinical outcome in a cohort of 347 alloSCT patients.SEP (n = 209) was associated with significantly reduced NRM (hazard ratio 0.61, 95% CI 0.38-0.96) and better overall survival (OS) after acute graft-versus-host disease (HR 0.59, 95% CI 0.37-0.93). Subgroup analyses showed that the NRM benefit was mainly found in patients with an intermediate endothelial activation and stress index (EASIX), while relapse risk was not affected. On day 100 post-alloSCT, patients receiving SEP had significantly higher levels of the rate-limiting enzyme of tryptophan metabolism, indoleamine 2,3-dioxygenase (IDO), higher kynurenine to tryptophan ratios as a proxy of IDO activity and tended to have lower levels of the endothelial injury marker ST2 (p = .055). No significant differences in interferon-gamma or IL18 levels were observed. These biomarker signatures suggest that the beneficial effects of SEP might be mediated by both endothelial protection and immunomodulation.Together, these data suggest that SEP improves NRM and OS post-alloSCT in particular in patients with intermediate endothelial risk and provide first mechanistic clues about its potential mode of action.
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000182099 650_7 $$2Other$$aallogeneic stem cell transplantation
000182099 650_7 $$2Other$$aendothelial damage
000182099 650_7 $$2Other$$aendothelial protection
000182099 650_7 $$2Other$$aimmunosuppression
000182099 650_7 $$2Other$$astatin
000182099 650_7 $$2Other$$athrombotic microangiopathy
000182099 7001_ $$0P:(DE-He78)0d054b6843ace36d1c965b6cb938d1c9$$aSchreck, Nicholas$$b1$$udkfz
000182099 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b2$$udkfz
000182099 7001_ $$aHegenbart, Ute$$b3
000182099 7001_ $$aSchönland, Stefan$$b4
000182099 7001_ $$aRadujkovic, Aleksandar$$b5
000182099 7001_ $$aSchmitt, Michael$$b6
000182099 7001_ $$aMüller-Tidow, Carsten$$b7
000182099 7001_ $$aOrsatti, Laura$$b8
000182099 7001_ $$aDreger, Peter$$b9
000182099 7001_ $$aLuft, Thomas$$b10
000182099 77318 $$2Crossref$$3journal-article$$a10.1111/eci.13883$$bWiley$$d2022-10-11$$n2$$tEuropean Journal of Clinical Investigation$$v53$$x0014-2972$$y2022
000182099 773__ $$0PERI:(DE-600)2004971-7$$a10.1111/eci.13883$$n2$$pe13883$$tEuropean journal of clinical investigation$$v53$$x0014-2972$$y2022
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