Tumor necrosis factor-alpha blockade for the treatment of acute GVHD. Academic Article uri icon

Overview

abstract

  • Despite posttransplantation immunosuppressive therapy, acute graft-versus-host disease (GVHD) remains a major cause of sickness and death. Tumor necrosis factor-alpha (TNF-alpha) is implicated in the pathophysiology of GVHD at several steps in the process. Infliximab is a genetically constructed immunoglobulin G1 (IgG1) murine-human chimeric monoclonal antibody that binds the soluble subunit and the membrane-bound precursor of TNF-alpha, blocking its interaction with receptors and causing lysis of cells that produce TNF-alpha. In this study we retrospectively evaluated 134 patients who had steroid-refractory acute GVHD. Of these, 21 who received infliximab as a single agent were analyzed. The overall response rate was 67% (n = 14), and 13 patients (62%) experienced complete response (CR). Five patients (24%) did not respond, and 2 (10%) had progressive GVHD. None had a toxic reaction to infliximab. Ten patients (48%) had 18 fungal infections, including Aspergillus species in 7 and Candida species in 10. Seventeen patients (81%) had bacterial infections, including 32 gram-positive and 8 gram-negative infections. Viral infections, primarily cytomegalovirus reactivation, occurred in 14 patients (67%). The Kaplan-Meier estimate of overall survival was 38%. In conclusion, infliximab was well tolerated and active for the treatment of steroid-resistant acute GVHD, particularly with gastrointestinal tract involvement. Survival after steroid-resistant acute GVHD continues to be problematic. The possibility of excessive fungal and other infections must be explored further.

publication date

  • April 6, 2004

Research

keywords

  • Antibodies, Monoclonal
  • Bone Marrow Transplantation
  • Graft vs Host Disease
  • Leukemia
  • Lymphoma
  • Stem Cell Transplantation
  • Tumor Necrosis Factor-alpha

Identity

Scopus Document Identifier

  • 3242756749

Digital Object Identifier (DOI)

  • 10.1182/blood-2003-12-4241

PubMed ID

  • 15069017

Additional Document Info

volume

  • 104

issue

  • 3