title: Tumor necrosis factor-alpha blockade for the treatment of acute GVHD.
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.
authors.affiliation: Department of Blood and Marrow Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. dcouriel@mdanderson.org
authors.forename: Daniel
authors.initials: D
authors.lastname: Couriel
authors.forename: Rima
authors.initials: R
authors.lastname: Saliba
authors.forename: Krystal
authors.initials: K
authors.lastname: Hicks
authors.forename: Cindy
authors.initials: C
authors.lastname: Ippoliti
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.forename: Issa
authors.initials: I
authors.lastname: Khouri
authors.forename: Borje
authors.initials: B
authors.lastname: Andersson
authors.forename: James
authors.initials: J
authors.lastname: Gajewski
authors.forename: Michele
authors.initials: M
authors.lastname: Donato
authors.forename: Paolo
authors.initials: P
authors.lastname: Anderlini
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.forename: Agueda
authors.initials: A
authors.lastname: Cohen
authors.forename: Thomas
authors.initials: T
authors.lastname: Martin
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000453:epidemiology; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D005260:Female; D006086:Graft vs Host Disease / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D000069285:Infliximab; D007938:Leukemia / Q000628:therapy*; D008223:Lymphoma / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000453:epidemiology; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014777:Virus Diseases / Q000453:epidemiology
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab