Treatment of steroid-resistant acute graft-versus-host disease with an anti-IL-2-receptor monoclonal antibody (BT 563) in children who received T cell-depleted, partially matched, related bone marrow transplants.
Fifteen children with steroid-resistant acute graft-versus-host disease (GVHD, grade II-IV) were treated with a murine monoclonal antibody (BT 563) specific for the alpha subunit of the interleukin-2 receptor (IL-2R). All had inherited diseases of the bone marrow and had received T cell-depleted marrow from a partially matched related donor. BT 563 antibody was given at a daily dose of 0.2 mg/kg. Treatment was continued until GVHD was controlled and the methylprednisolone administration was tapered to < or = 2 mg/kg/day. No side-effects were noted. Eleven of the 15 patients reached complete remission and a partial remission occurred in two. This good response rate was associated with early treatment (mean time after GVHD onset 7.7 +/- 5.3 days) and prolonged treatment (mean 25.9 +/- 10.6 days) compared with previously published data on BT 563 antibody usage. Relapses occurred in six of the 13 responders but a further remission was induced by the same treatment. Chronic GVHD developed in six cases and one of them died of GVHD-associated infection. Ten of the 15 patients are long-term survivors and are free of chronic GVHD. The results of this pilot study indicate that early and lengthy treatment with anti-IL-2R monoclonal antibody is both safe and effective against steroid-resistant GVHD in young children and indicate that further trials of anti-IL-2R antibody as first-line therapy of acute GVHD are warranted.
Herbelin
C
C
Département de Pédiatrie, Hôpital des Enfants Malades, Paris, France.
Stephan
J L
JL
Donadieu
J
J
Le Deist
F
F
Racadot
E
E
Wijdenes
J
J
Fischer
A
A
D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000628:therapy*; D006801:Humans; D007223:Infant; D008212:Lymphocyte Depletion; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D010865:Pilot Projects; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2; D008775:Methylprednisolone