Ruxolitinib as Salvage Therapy in Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric Hematopoietic Stem Cell Transplant Patients.
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 5 mg twice daily for children ≥ 25 kg or 2.5 mg twice daily if <25 kg. 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 (n = 13) included grades 3 to 4 elevated alanine transaminase (n = 7), grades 3 to 4 neutropenia (n = 5), and grade 4 thrombocytopenia (n = 3). Infectious complications in patients included for response analysis (n = 11) were Epstein-Barr viremia (n = 2), adenovirus (n = 2), BK (n = 3), bacterial infections (n = 6), and fungal infections (n = 1). 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.
Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: Pooja.khandelwal@cchmc.org.
Pooja
P
Khandelwal
Division of Pharmacy, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Ashley
A
Teusink-Cross
Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Stella M
SM
Davies
Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Adam S
AS
Nelson
Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Christopher E
CE
Dandoy
Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Javier
J
El-Bietar
Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Rebecca A
RA
Marsh
Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Ashish R
AR
Kumar
Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Michael S
MS
Grimley
Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Sonata
S
Jodele
Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Kasiani C
KC
Myers
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D008297:Male; D009570:Nitriles; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines; D016879:Salvage Therapy / Q000379:methods*; D019172:Transplantation Conditioning / Q000379:methods*
D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib
Jak inhibitor; Ruxolitinib; SR graft-versus-host disease; SR-GVHD in children