Statin‐based endothelial prophylaxis and outcome after allogeneic stem cell transplantation

Abstract

Background Allogeneic 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. Methods 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. Results 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. Conclusions 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.

Reeling in complement in transplant‐associated thrombotic microangiopathy: You're going to need a bigger boat

“…N‐acetylcysteine is used in acetaminophen toxicity and has known antioxidant effects that are of potential relevance to endothelial injury in TA‐TMA 60,61 . Statin use in TA‐TMA was adopted from cardiology experiences and published data on endothelial injury with obesity 62–64 . A new prospective study (NCT05524246) was recently opened to examine pravastatin prophylaxis to reduce endothelial injury in pediatric HSCT recipients with elevated body mass index.…”

“…60,61 Statin use in TA-TMA was adopted from cardiology experiences and published data on endothelial injury with obesity. [62][63][64] A new prospective study (NCT05524246) was recently opened to examine pravastatin prophylaxis to reduce endothelial injury in pediatric HSCT recipients with elevated body mass index.…”

From support to therapy: rethinking the role of nutrition in acute graft-versus-host disease

“…In one retrospective study, pravastin was used for endothelial protection and reduced non-relapse mortality after HSCT, though not due to a lower incidence of aGVHD. However, patients who did suffer from aGVHD benefited more from statin treatment than patients without aGVHD ( 49 ). A murine study found that atorvastatin reduced aGVHD lethality without affecting GVL effect when both donor and recipient were dosed with the drug.…”