PHASE-I TRIAL OF INTERLEUKIN-2 AFTER UNMODIFIED HLA-MATCHED SIBLING BONE-MARROW TRANSPLANTATION FOR CHILDREN WITH ACUTE-LEUKEMIA

Allogeneic bone marrow transplantation (BMT) for advanced acute leukem ia is associated with a high risk of relapse. It is postulated that in terleukin-2 (IL-2) administered after BMT might induce or amplify a gr aft-versus-leukemia effect and thereby reduce the relapse rate. To ide ntify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) with out active graft-versus-host disease (GVHD) off immunosuppressive agen ts after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 pa tients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m(2)/d representing levels I, II, and III) for 5 days by con tinuous intravenous infusion (CIV). After 6 days of rest, they receive d maintenance IL-2 (0.9 x 10(6) IU/m(2)/d) for 10 days by CIV infusion . Levels I and II were well-tolerated, but, of 6 patients at level III , 1 developed pulmonary infiltrates, 1 developed hypotension (both res olved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. Chronic GVHD developed in 1 patient at level I and 4 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56(+) and CD8(+) cel ls. Ten patients remain in CR at 5+ to 67+ months. Thus. a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. I ts clinical activity will be assessed in a phase II trial. (C) 1996 by The American Society of Hematology.