Advancing prophylaxis and management of acute graft-versus-host disease in the era of novel therapies

Allogeneic hematopoietic cell transplantation is a cornerstone treatment for many high-risk hematological malignancies, yet acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and non-relapse mortality. Recent advances, including post-transplant cyclophosphamide (PTCy), anti-thymocyte globulin, abatacept, and targeted therapies such as ruxolitinib, have expanded options for preventing and treating aGVHD. However, important questions remain regarding the definition and early identification of steroid-refractory disease, the clinical integration of biomarkers, the optimal sequencing of therapies, and the balance between GVHD control, immune recovery, relapse risk, and infectious complications. Emerging clinical trials and real-world studies are beginning to clarify the efficacy and safety of novel agents, but evidence remains heterogeneous across donor sources, conditioning regimens, age groups, and disease settings. Further investigation is needed to establish personalized, evidence-based approaches for patients at high risk of aGVHD and for those with refractory or recurrent disease.

This Research Topic aims to evaluate contemporary strategies for the prevention, risk assessment, and management of aGVHD after allogeneic hematopoietic cell transplantation. It will examine how novel and conventional therapies can be optimally integrated, whether biomarker-guided algorithms can improve treatment selection and outcomes, and how therapeutic strategies can minimize toxicity without compromising graft-versus-leukemia effects or immune reconstitution. The Research Topic will also address clinically relevant differences between adult and paediatric populations and identify priorities for future prospective studies.

To gather further insights into the prevention and treatment of aGVHD across diverse transplantation settings, we welcome contributions addressing, but not limited to, the following themes:
• Novel prophylaxis strategies, including PTCy, anti-thymocyte globulin, abatacept, and combination approaches
• Definitions, predictors, and early recognition of steroid-refractory aGVHD
• Ruxolitinib, belumosudil, ibrutinib, and other second-line or later-line therapies
• Biomarker-guided risk stratification, monitoring, and treatment algorithms
• Sequencing and combination of conventional and emerging therapies
• Management of refractory, recurrent, or organ-specific aGVHD
• Infection prevention and management during immunosuppressive treatment
• Effects of treatment on relapse, non-relapse mortality, and immune reconstitution
• Real-world evidence and outcomes in high-risk, adult, and paediatric populations
• Patient-reported outcomes, quality of life, and long-term survivorship

Appendix: We welcome preclinical and clinical studies, trial updates, meta-analyses, comprehensive reviews, expert perspectives, and real-world evidence.