Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5524348 | Biology of Blood and Marrow Transplantation | 2017 | 6 Pages |
â¢Ruxolitinib has a 45% overall response rate as salvage therapy in children with steroid-refractory acute graft-versus-host disease.â¢Ruxolitinib is associated with significant but reversible adverse effects such as cytopenias and transaminitis.
We describe our retrospective clinical experience with ruxolitinib for steroid-refractory acute graft-versus-host disease (GVHD) in pediatric allogeneic hematopoietic stem cell transplant (HSCT) patients. Ruxolitinib was administered orally at 5âmg twice daily for children ⥠25âkg or 2.5âmg twice daily if <25âkg. We excluded patients who received new immune suppressive agents within 2 weeks before initiation of ruxolitinib from response analysis. Patients were called a treatment failure if ruxolitinib was stopped before completion of 4 weeks of therapy because of adverse effects and not because of progression of acute GVHD. Thirteen patients received ruxolitinib, and 11 patients were assessable for response. One patient achieved a complete response, 4 had a partial response, and 2 had no response at 4 weeks after the first ruxolitinib dose. Four patients were treatment failures. Overall response rate was 45%. Adverse effects (nâ=â13) included grades 3 to 4 elevated alanine transaminase (nâ=â7), grades 3 to 4 neutropenia (nâ=â5), and grade 4 thrombocytopenia (nâ=â3). Infectious complications in patients included for response analysis (nâ=â11) were Epstein-Barr viremia (nâ=â2), adenovirus (nâ=â2), BK (nâ=â3), bacterial infections (nâ=â6), and fungal infections (nâ=â1). Seven of 13 patients were alive at a median follow-up of 401 days (range, 219 to 969) after HSCT. We observed a high rate of reversible adverse effects in children with steroid-refractory acute GVHD and a fair overall response of ruxolitinib as a salvage therapeutic agent. Further pharmacokinetic studies are needed to determine the best-tolerated dose of ruxolitinib that will achieve efficacy without significant adverse effects.