Immediate versus delayed short-course ruxolitinib for acute GVHD prophylaxis after myeloablative allogeneic hematopoietic stem cell transplantation.

BACKGROUND

The optimal timing of ruxolitinib initiation for acute graft-versus-host disease (aGVHD) prophylaxis after myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains undefined, particularly within anti-thymocyte globulin (ATG)-based platforms. This study compared immediate versus delayed short-course ruxolitinib initiation using a concurrent two-strategy design.

METHODS

This single-center, retrospective, concurrent two-strategy cohort study enrolled 39 consecutive patients aged 15-65 years with hematologic malignancies who received standard "Beijing Protocol" backbone plus a 14-day short-course ruxolitinib. Patients were non-randomly assigned to immediate (day +1; n = 19) or delayed (at confirmed neutrophil engraftment; median day +13; n = 20) initiation. Haploidentical transplantation and ATG use were perfectly collinear in this cohort, complicating attribution of outcome differences. Co-primary endpoints were 100-day cumulative incidence of grade II-IV aGVHD and 2-year overall survival (OS). A 1:1 propensity score matching (PSM) analysis (12 pairs) served as a sensitivity analysis. Given the limited sample size, multivariable models were constructed as exploratory analyses and should be interpreted with caution.

RESULTS

Delayed initiation was associated with lower 100-day grade II-IV aGVHD (10.0% vs. 42.1%, P = 0.031), lower cytomegalovirus (CMV) reactivation (35.0% vs. 73.7%, P = 0.025), reduced grade ≥3 hematologic toxicity (35.0% vs. 68.4%, P = 0.043), and superior 2-year OS rate (90.0% vs. 57.9%, P = 0.012). PSM confirmed these findings (aGVHD: 8.3% vs. 41.7%, P = 0.039; OS: 91.7% vs. 58.3%, P = 0.028). In the exploratory haploidentical subgroup (n = 26), grade II-IV aGVHD was 11.8% vs. 55.6% (P = 0.028) and OS was 94.1% vs. 55.6% (P = 0.006). In exploratory multivariable models, immediate initiation was associated with higher aGVHD risk [adjusted subdistribution hazard ratio (sHR) 2.31, 95% CI 1.15-4.64, P = 0.019] and higher NRM (adjusted sHR 4.65, 95% CI 1.47-14.72, P = 0.009). Relapse risk was not significantly different (adjusted sHR 2.17, 95% CI 0.85-5.56, P = 0.095). Pre-transplant measurable residual disease (MRD) positivity was associated with inferior OS (adjusted hazard ratio [HR] 7.81, 95% CI 1.12-54.32, P = 0.038). Median follow-up was 42.1 months. Interpretation of the CMV reactivation difference is limited by the absence of donor and recipient CMV serostatus data.

CONCLUSION

Delaying short-course ruxolitinib until neutrophil engraftment was associated with reduced aGVHD and NRM and improved survival after myeloablative allo-HSCT. No statistically significant difference in relapse risk was observed, although a clinically meaningful difference cannot be excluded. These findings warrant confirmation in a multicenter randomized trial with adequate sample size, stratified by donor type and pre-transplant MRD.