Escalation to High-Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease.
Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those used in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. Increased toxicity was not observed until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10 and 100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, whereas those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (P = .008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose-escalation strategy remains unclear, because outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD.
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee. Electronic address: brandon.triplett@stjude.org.
Brandon M
BM
Triplett
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
Hani I
HI
Kuttab
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
Guolian
G
Kang
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee.
Wing
W
Leung
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects; D011089:Polydeoxyribonucleotides / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D019653:Myeloablative Agonists; D011089:Polydeoxyribonucleotides; C036901:defibrotide
Defibrotide; Hematopoietic cell transplantation; Hepatic veno-occlusive disease