PMID- 15069017
OWN - NLM
STAT- MEDLINE
DCOM- 20040830
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 104
IP  - 3
DP  - 2004 Aug 1
TI  - Tumor necrosis factor-alpha blockade for the treatment of acute GVHD.
PG  - 649-54
AB  - 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.
FAU - Couriel, Daniel
AU  - Couriel D
AD  - Department of Blood and Marrow Transplantation, University of Texas M.D. Anderson 
      Cancer Center, Houston, TX 77030, USA. dcouriel@mdanderson.org
FAU - Saliba, Rima
AU  - Saliba R
FAU - Hicks, Krystal
AU  - Hicks K
FAU - Ippoliti, Cindy
AU  - Ippoliti C
FAU - de Lima, Marcos
AU  - de Lima M
FAU - Hosing, Chitra
AU  - Hosing C
FAU - Khouri, Issa
AU  - Khouri I
FAU - Andersson, Borje
AU  - Andersson B
FAU - Gajewski, James
AU  - Gajewski J
FAU - Donato, Michele
AU  - Donato M
FAU - Anderlini, Paolo
AU  - Anderlini P
FAU - Kontoyiannis, Dimitrios P
AU  - Kontoyiannis DP
FAU - Cohen, Agueda
AU  - Cohen A
FAU - Martin, Thomas
AU  - Martin T
FAU - Giralt, Sergio
AU  - Giralt S
FAU - Champlin, Richard
AU  - Champlin R
LA  - eng
PT  - Journal Article
DEP - 20040406
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - B72HH48FLU (Infliximab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal/adverse effects/*therapeutic use
MH  - Bacterial Infections/epidemiology
MH  - Bone Marrow Transplantation/*adverse effects
MH  - Female
MH  - Graft vs Host Disease/*therapy
MH  - Histocompatibility Testing
MH  - Humans
MH  - Infliximab
MH  - Leukemia/*therapy
MH  - Lymphoma/*therapy
MH  - Male
MH  - Middle Aged
MH  - Mycoses/epidemiology
MH  - Retrospective Studies
MH  - *Stem Cell Transplantation/*adverse effects
MH  - Transplantation, Homologous
MH  - Tumor Necrosis Factor-alpha/*immunology
MH  - Virus Diseases/epidemiology
EDAT- 2004/04/08 05:00
MHDA- 2004/08/31 05:00
CRDT- 2004/04/08 05:00
PHST- 2004/04/08 05:00 [pubmed]
PHST- 2004/08/31 05:00 [medline]
PHST- 2004/04/08 05:00 [entrez]
AID - S0006-4971(20)43590-6 [pii]
AID - 10.1182/blood-2003-12-4241 [doi]
PST - ppublish
SO  - Blood. 2004 Aug 1;104(3):649-54. doi: 10.1182/blood-2003-12-4241. Epub 2004 Apr 
      6.