title: Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia.
abstract: In contrast to severe aplastic anemia (sAA), the appropriate management of patients with moderate pancytopenia is unclear. In this study, we examined the efficacy of a humanized monoclonal antibody recognizing interleukin-2 receptor (daclizumab), which has proven to be a successful immunosuppressive agent in solid organ and bone marrow transplantation. We treated 17 patients with moderate aplastic anemia (mAA) with 1 mg/kg every 2 weeks for 3 months. mAA was defined as depression of 2 of the 3 blood counts: absolute neutrophil count 1200/mm3 or less, platelet count 70,000/mm3 or less, hemoglobin level 8.5 g/dL or lower, and absolute reticulocyte count 60,000/mm3 or less. The primary end point of our protocol was a hematologic response in at least one affected peripheral blood value. Daclizumab had little toxicity. Six of the 16 (38%) evaluable patients responded to treatment. Two patients with previously chronic disease showed complete return of normal counts, which were sustained for more than 2 years following treatment. Four patients had single-lineage responses. Two previously transfusion-dependent patients became transfusion independent; one patient with many neutropenia-related infections had a normal neutrophil count following treatment. Daclizumab appears safe; its efficacy in this pilot protocol suggests that expanded study of this monoclonal antibody in immune-mediated bone marrow failure syndrome is warranted.
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Sloand
authors.forename: Olga
authors.initials: O
authors.lastname: Nunez
authors.forename: Carol
authors.initials: C
authors.lastname: Boss
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000188:drug therapy*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001772:Blood Cell Count; D002648:Child; D000077561:Daclizumab; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015375:Receptors, Interleukin-2 / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D000077561:Daclizumab