N-acetylcysteine in the treatment of steroid-resistant acute graft-versus-host-disease: preliminary results. Gruppo Italiano Trapianto di Midollo Osseo (GITMO).
BACKGROUND
Acute graft-versus-host disease (GVHD) results from reactivity of donor immunocompetent cells versus host tissues. Its pathogenesis involves co-stimulatory molecules, cytokines, free radicals, and oxidative stress products. N-Acetylcysteine (NAC) is an antioxidant that inhibits the B7-1/CD28 expression in vitro, and it may contrabalance the effects of free radicals and oxidative stress; it has been tested in eight patients with steroid-resistant acute GVHD.


METHODS
NAC was given at the dose of 150 mg/kg bolus intravenously, followed by 50 mg/kg intravenous continuous infusion over 3 weeks or less up, to clinical GVHD resolution. In four patients, flow cytometric analysis of co-stimulatory molecules was performed on peripheral mononuclear cells before and after NAC therapy.


RESULTS
We achieved prompt response in six patients: four had complete response, two partial response. Two patients died of acute GVHD, and four of intercurrent disease. We noticed significant decrease in CD80, CD25, and CD8+ cells after NAC therapy.


CONCLUSIONS
NAC therapy is feasible; it may give response in steroid-resistant acute GVHD. More extensive studies are needed to confirm these data.
Colombo
A A
AA
Istituto di Ematologia, IRCCS Policlinico S. Matteo, Pavia, Italy. aa.colombo@smatteo.pv.it
Alessandrino
E P
EP
Bernasconi
P
P
Arcese
G W
GW
Rabusin
M
M
Bacigalupo
A
A
Bernasconi
C
C
D000111:Acetylcysteine / Q000627:therapeutic use*; D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged
D000305:Adrenal Cortex Hormones; D000975:Antioxidants; D000111:Acetylcysteine