Tumor necrosis factor-alpha blockade for the treatment of acute GVHD.
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.
Couriel
Daniel
D
Department of Blood and Marrow Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. dcouriel@mdanderson.org
Saliba
Rima
R
Hicks
Krystal
K
Ippoliti
Cindy
C
de Lima
Marcos
M
Hosing
Chitra
C
Khouri
Issa
I
Andersson
Borje
B
Gajewski
James
J
Donato
Michele
M
Anderlini
Paolo
P
Kontoyiannis
Dimitrios P
DP
Cohen
Agueda
A
Martin
Thomas
T
Giralt
Sergio
S
Champlin
Richard
R
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
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab