TY - JOUR
T1 - Tumor necrosis factor-α blockade for the treatment of acute GVHD
AU - Couriel, Daniel
AU - Saliba, Rima
AU - Hicks, Krystal
AU - Ippoliti, Cindy
AU - De Lima, Marcos
AU - Hosing, Chitra
AU - Khouri, Issa
AU - Andersson, Borje
AU - Gajewski, James
AU - Donato, Michele
AU - Anderlini, Paolo
AU - Kontoyiannis, Dimitrios P.
AU - Cohen, Agueda
AU - Martin, Thomas
AU - Giralt, Sergio
AU - Champlin, Richard
PY - 2004/8/1
Y1 - 2004/8/1
N2 - Despite posttransplantation immunosuppressive therapy, acute graft-versus-host disease (GVHD) remains a major cause of sickness and death. Tumor necrosis factor-α (TNF-α) 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-α, blocking its interaction with receptors and causing lysis of cells that produce TNF-α. 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 Aspargillus 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.
AB - Despite posttransplantation immunosuppressive therapy, acute graft-versus-host disease (GVHD) remains a major cause of sickness and death. Tumor necrosis factor-α (TNF-α) 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-α, blocking its interaction with receptors and causing lysis of cells that produce TNF-α. 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 Aspargillus 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.
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U2 - 10.1182/blood-2003-12-4241
DO - 10.1182/blood-2003-12-4241
M3 - Article
C2 - 15069017
AN - SCOPUS:3242756749
SN - 0006-4971
VL - 104
SP - 649
EP - 654
JO - Blood
JF - Blood
IS - 3
ER -