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 diseas e (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 contin ued until GVHD was controlled and the methylprednisolone administratio n was tapered to less than or equal to 2 mg/kg/day. No side-effects we re noted. Eleven of the 15 patients reached complete remission and a p artial remission occurred in two. This good response rate was associat ed with early treatment (mean time after GVHD onset 7.7 +/- 5.3 days) and prolonged treatment (mean 25.9 +/- 10.6 days) compared with previo usly 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 survi vors and are free of chronic GVHD. The results of this pilot study ind icate that early and lengthy treatment with anti-IL-2R monoclonal anti body is both safe and effective against steroid-resistant GVHD in youn g children and indicate that further trials of anti-IL-2R antibody as first-line therapy of acute GVHD are warranted.