Sequential use of three monoclonal antibodies in corticosteroid-resistant acute GVHD: a multicentric pilot study including 15 patients.
We previously demonstrated the potential of anti-IL-2R and anti-TNF alpha moAbs in the treatment of acute graft-versus-host disease (GVHD). However, one major problem was the recurrence of acute GVHD on treatment discontinuation. To target the two main effectors of acute GVHD lesions, T and NK cells on the one hand and TNF alpha on the other, we combined anti-CD2 and anti-TNF alpha moAbs. Then to prevent acute GVHD recurrence, we administered anti-IL-2R moAbs known for their inhibitory effect on activated cells. We included 15 patients with steroid-resistant acute GVHD. Seven were grafted from a genotypically-identical sibling, 5 from HLA-matched unrelated donors and 3 from partially-matched related donor. Prophylaxis of acute GVHD consisted of cyclosporin A +/- methotrexate or corticosteroids. Before treatment 6 patients had grade II, 2 patients grade III and 7 patients grade IV acute GVHD. Anti-TNF alpha (B-C7) moAbs (10 mg/day/4 days) were combined with anti-CD2 (B-E2) moAbs (10 mg/day/10 days) on the fifth day (day 5), anti-IL-2 receptor (B-B10) moAbs were given at 10 mg/day/10 days followed by 5 mg every other day for another 50 days. On day 15, 5 patients achieved a complete remission, 4 a very good partial response (62% a good response), 2 had a partial response and 4 did not respond. GVHD recurred in 4 of the 9 responders, although anti-IL-2R moAb treatment was maintained. Three patients are long-term survivors without chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
Racadot
E
E
Centre Régional de Transfusion Sanguine, Besançon, France.
Milpied
N
N
Bordigoni
P
P
Cahn
J Y
JY
Plouvier
E
E
Lioure
B
B
Lutz
P
P
Wijdenes
J
J
Herve
P
P
D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000276:immunology; D018801:CD2 Antigens / Q000276:immunology*; D002648:Child; D016207:Cytokines / Q000097:blood; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D016207:Cytokines; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha