title: A pilot dose-escalating study of alemtuzumab plus cyclosporine for patients with bone marrow failure syndrome.
abstract: The pathogenesis of bone marrow failure syndrome (BMFS) involves both T- and B-cells. Since alemtuzumab (ALM) is a monoclonal anti-CD52 antibody that targets both cell types, we assessed the effects of treatment with ALM and cyclosporine (CS) on 19 patients with BMFS (median age 48 years; range, 16-74 years), including 14 with severe/very severe aplastic anemia (AA), 3 with transfusion-dependent AA and 1 each with myelodysplastic syndrome (MDS) and pure red cell aplasia (PRCA). The dose of ALM was escalated from dose cohort I (10mg on day 1, 20mg on day 2, and 30 mg on day 3) to dose cohort II (30 mg/d for 3 days) plus CS for at least 6 months. Thirteen patients were in dose cohort I and 6 were in dose cohort II. Five patients (23.5%) had a complete response (CR), 2 (11.8%) had a partial response (PR), and 12 (64.7%) had no response, making the overall response rate 36.8% (7/19). The overall response rates in dose cohorts I and II were 46.2% (6/13) and 16.7% (1/6), respectively. Among the 17 patients with AA, the ORR was 35.3% (6/17), 50.0% (6/12) in dose cohort 1 and 0 (0/5) in dose cohort II. Most responsive patients responded within 3 months. Among responders, median time to initial response was 2.07 months (95% CI, 1.40-2.75 months) and median time from initial response to complete response in complete responders was 9.33 months (95% CI, 0.0-31.71 months). The 2-year survival rate was 81.6%. These findings indicate that ALM-CS should be one option for IST in BMFS, and that 60 mg of ALM may be sufficient compared with the higher dose (90 mg).
authors.affiliation: Division of Hematology-Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714, Republic of Korea.
authors.forename: Hawk
authors.initials: H
authors.lastname: Kim
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Min
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Baek
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Shin
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Lee
authors.forename: Eui-Kyu
authors.initials: EK
authors.lastname: Noh
authors.forename: Mee-Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Jae-Hoo
authors.initials: JH
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000741:Anemia, Aplastic; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D001855:Bone Marrow Diseases / Q000188:drug therapy*; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes; D010865:Pilot Projects; D012010:Red-Cell Aplasia, Pure; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D016572:Cyclosporine