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

Area of Science:

• Hematology
• Immunology
• Transplantation Medicine

Background:

• Allogeneic haematopoietic stem cell transplantation (alloSCT) is a curative therapy for hematologic malignancies.
• Nonrelapse mortality (NRM) remains a significant challenge post-alloSCT, with endothelial dysfunction being a major contributor.
• Improved management of transplant-associated adverse events has been achieved, but NRM persists.

Purpose of the Study:

• To evaluate the impact of statin-based endothelial prophylaxis (SEP) on clinical outcomes in patients undergoing alloSCT.
• To investigate the effect of SEP on nonrelapse mortality (NRM) and overall survival (OS).
• To explore potential mechanisms underlying the effects of SEP, including endothelial protection and immunomodulation.

Main Methods:

• Retrospective analysis of 347 alloSCT patients.
• Implementation of SEP as standard of care in the transplant center.
• Assessment of clinical outcomes including NRM and OS.
• Biomarker analysis including indoleamine 2,3-dioxygenase (IDO) activity, kynurenine to tryptophan ratios, and ST2 levels.

Main Results:

• SEP was associated with significantly reduced NRM (HR 0.61) and improved OS (HR 0.59).
• The NRM benefit was primarily observed in patients with intermediate endothelial activation and stress index (EASIX).
• SEP was linked to increased IDO activity and tended to lower ST2 levels, suggesting endothelial protection and immunomodulation.

Conclusions:

• SEP improves NRM and OS post-alloSCT, particularly in patients with intermediate endothelial risk.
• The findings provide mechanistic insights into SEP's potential mode of action, involving endothelial protection and immunomodulation.
• SEP represents a promising strategy to mitigate NRM in alloSCT recipients.