Efficacy and safety of ruxolitinib for graft-versus-host disease prophylaxis in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis.

Introduction: Graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite standard prophylaxis, acute and chronic GVHD incidence remains high. Ruxolitinib, a Janus kinase inhibitor (JAK1/2), shows promise in treating steroid-refractory GVHD. However, its efficacy and safety as an adjunct to standard prophylactic regimens remain subjects of debate. This meta-analysis aims to evaluate the efficacy and safety of ruxolitinib when used as an adjunct to GVHD prophylaxis following allo-HSCT. Methods: Comprehensive studies were searched in PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov. Outcomes measures included the incidence rates of acute/chronic GVHD, overall survival (OS), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation events. Pooled proportions with 95% confidence intervals (CIs) were calculated using random/fixed-effects models. Results: A total of 12 studies, including 406 patients, were analyzed. Most of these studies were non-randomized. The pooled incidence of grade II-IV and III-IV acute GVHD was 10.4% (95% CI: 7.3-13.5%) and 2.9% (0.6-5.2%), respectively, with no heterogeneity ( Discussion: Ruxolitinib as GVHD prophylaxis significantly reduces acute GVHD severity and maintains favorable survival outcomes, likely due to Janus kinase and signal transducer and activator (JAK-STAT) pathway inhibition. However, elevated CMV/EBV reactivation rates the need for vigilant monitoring. These findings support ruxolitinib's role as a promising adjunct in GVHD prevention, warranting further randomized trials to confirm long-term safety and efficacy.