Defibrotide for the treatment of hepatic veno-occlusive disease in children.
BACKGROUND
This retrospective report describes experience with defibrotide in children with hepatic veno-occlusive disease (HVOD) following hematopoietic progenitor cell transplant (HPCT) in a single institution.


METHODS
Children who had undergone HPCT between February 1999 and June 2001 and between July 2003 and September 2004 and who received defibrotide during their admission were identified. Demographic data and information regarding the clinical course of these patients were abstracted from their health records.


RESULTS
Fourteen children (mean age: 9.3 years; range: 0.4-18.1) who underwent HPCT during the study period received defibrotide for the treatment of HVOD; nine were girls. Most patients underwent HPCT for hematologic malignancies (8/14) and received matched unrelated donor transplants (8/14). Conditioning regimens included cyclophosphamide with total body irradiation (5/14) and busulfan followed by cyclophosphamide (7/14). HVOD was diagnosed on transplant day -4 to +33 (median: +10.5); defibrotide was started on transplant day -4 to +40 (median: +12). The median initial defibrotide dose was 33 mg/kg/day (11-40 mg/kg/day); the median maximum defibrotide dose was 38.5 mg/kg/day (11-81 mg/kg/day). The median duration of defibrotide therapy was 16 days (4-37 days). Defibrotide was discontinued due to clinical improvement (9), death (3), drug unavailability (1), and neurological toxicity (1). Gastrointestinal hemorrhage was observed in two patients and intra-cranial hemorrhage was observed in one patient during defibrotide therapy. The survival rate to day +100 was 79%.


CONCLUSIONS
Defibrotide appears to be an effective and relatively safe treatment for children with HVOD.
Bulley
Sean R
SR
Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Strahm
Brigitte
B
Doyle
John
J
Dupuis
L Lee
LL
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006504:Hepatic Veno-Occlusive Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007223:Infant; D008297:Male; D011089:Polydeoxyribonucleotides / Q000627:therapeutic use*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
D011089:Polydeoxyribonucleotides; C036901:defibrotide