1. ¹Section of Pediatric Hematology/Oncology, Department of Pediatrics, Yale University, New Haven, CT, USA
2. ²Division of Pediatric Stem Cell Transplantation, Texas Transplant Institute, San Antonio, TX, USA
3. ³Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
4. ⁴Division of Pediatric Hematology/Oncology, Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO, USA
5. ⁵Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA

Correspondence: Dr AL Gilman, Pediatric Blood and Marrow Transplantation, UNC School of Medicine, CB 7220, Chapel Hill, NC 27599-7220, USA. E-mail: agilman@med.unc.edu

Received 8 May 2006; Revised 14 May 2007; Accepted 14 May 2007; Published online 9 July 2007.

Abstract

GVHD remains a significant complication of allogeneic hematopoietic stem cell transplantation. Tumor necrosis factor- (TNF-) is a major mediator of GVHD pathogenesis. Infliximab inhibits the binding of TNF- 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.