Acute and chronic graft-versus-host disease (GVHD) remain major barriers to successful hematopoietic stem cell transplantation (SCT). TNF-alpha has been implicated in the pathogenesis of GVHD and TNF-alpha blockade has been explored for treatment of GVHD. The development of a chimeric mouse/human monoclonal antibody (infliximab) which binds to cells producing TNF-alpha, allowing for not only the neutralization of TNF-alpha but also lysis of the cells producing the TNF-alpha, makes this an attractive drug to explore in GVHD. We report on 11 patients with acute GVHD who were treated with infliximab after failing other therapies. The survival was very poor, in keeping with previously published reports of steroid-refractory acute GVHD. Two patients with severe diarrhea from acute GI GVHD resolved their symptoms after treatment with infliximab. Only these two patients survived. It appears that of all acute GVHD manifestations, gastrointestinal GVHD may be more responsive to treatment with infliximab than others. Caution is recommended when using this agent since it may exacerbate active infections, particularly aspergillosis. Furthermore, we do not know the correct dose or schedule to use with this drug. Given these data, controlled studies assessing dose and timing of administration may be warranted to study infliximab in acute GVHD.
Copyright 2003 Wiley-Liss Inc.