Infliximab for GVHD therapy in children.
GVHD remains a significant complication of allogeneic hematopoietic stem cell transplantation. Tumor necrosis factor-alpha (TNF-alpha) is a major mediator of GVHD pathogenesis. Infliximab inhibits the binding of TNF-alpha with its cellular receptors and has been associated with encouraging responses in adults with severe GVHD. We retrospectively evaluated the efficacy and safety of infliximab 10 mg/kg i.v. once a week for a median of eight doses (range 1-162) in 24 children with steroid-resistant GVHD. The overall response rate in 22 evaluable children was 82% (12 CR+6 PR). Among those patients with acute GVHD, both skin and gastrointestinal involvement responded well to infliximab; however long-term outcome was poor. While infliximab may be useful to acutely control GVHD manifestations, GVHD recurs commonly upon discontinuation of infliximab. Within 100 days of the final infliximab dose, 77% of patients had bacterial infections, 32% had viral infections and 13.6% had probable or proven non-candidal invasive fungal infections. Infliximab appears to be well-tolerated and to have activity in steroid-resistant GVHD. Controlled studies to assess the pharmacokinetics and most effective dosing regimen of infliximab for the treatment of GVHD are warranted.
Sleight
B S
BS
Section of Pediatric Hematology/Oncology, Department of Pediatrics, Yale University, New Haven, CT, USA.
Chan
K W
KW
Braun
T M
TM
Serrano
A
A
Gilman
A L
AL
D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D000069285:Infliximab; D008297:Male; D009894:Opportunistic Infections / Q000139:chemically induced; D012189:Retrospective Studies; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D000069285:Infliximab