title: Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia.
abstract: Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/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 resolved), 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. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. 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. Its clinical activity will be assessed in a phase II trial.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Robinson
authors.forename: J E
authors.initials: JE
authors.lastname: Sanders
authors.forename: M C
authors.initials: MC
authors.lastname: Benyunes
authors.forename: K
authors.initials: K
authors.lastname: Beach
authors.forename: C
authors.initials: C
authors.lastname: Lindgren
authors.forename: J A
authors.initials: JA
authors.lastname: Thompson
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: A
authors.initials: A
authors.lastname: Fefer
mesh_terms: D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D016026:Bone Marrow Transplantation; D019002:CD56 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000008:administration & dosage*; D007951:Leukemia, Myeloid / Q000628:therapy*; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D009679:Nuclear Family; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D019002:CD56 Antigen; D006680:HLA Antigens; D007376:Interleukin-2