Infliximab treatment for steroid-refractory acute graft-versus-host disease.
OBJECTIVE
Tumor necrosis factor a is one of the principal cytokines involved in the pathogenesis of acute graft-versus-host-disease (GVHD). Infliximab is an antibody to this cytokine.


METHODS
We performed a retrospective analysis to evaluate the activity of infliximab in 32 patients with severe steroid-refractory acute GVHD. The patients received a median of 3 weekly courses of infliximab. The main organs involved in the patients were skin (n=2) liver (n=1), bowel (n=19), liver and bowel at the same stage (n=10).


RESULTS
Nineteen out 32 patients (59%) responded to infliximab with 6 (19%) complete and 13 (40%) partial responses. Age younger than 35 years, intestinal involvement and a longer time between hematopoietic stem cell transplantation and infliximab administration were factors predicting a favorable response. Infective episodes developed in 23/32 (72%) patients. All the 13 unresponsive patients died of GVHD shortly after infliximab. Thirteen of 19 responsive patients were alive at a median follow-up of 449 days (range 155-842) after infliximab, with no signs of chronic GVHD (n=5), limited (n=5) or extensive involvement (n=3). Six patients who responded subsequently died, one of chronic lung GVHD, the others of vascular complications or infections (2 fungal diseases).


CONCLUSIONS
We conclude that infliximab is active in the treatment of severe steroid-refractory acute GVHD, particularly when the intestine is involved. Infections commonly followed its administration. The clinical activity of infliximab and the possibility that it increases the risk of infections are worth investigating in prospective trials.
Patriarca
Francesca
F
Division of Haematology, Dept. of Clinical and Morphological Research, University of Udine, Italy. francesca.patriarca@med.uniud.it <francesca.patriarca@med.uniud.it>
Sperotto
Alessandra
A
Damiani
Daniela
D
Morreale
Giuseppe
G
Bonifazi
Francesca
F
Olivieri
Attilio
A
Ciceri
Fabio
F
Milone
Giuseppe
G
Cesaro
Simone
S
Bandini
Giuseppe
G
Dini
Giorgio
G
Corradini
Paolo
P
Fanin
Renato
R
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013256:Steroids / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab