title: Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease.
abstract: BU and CY (BU/CY; 200 mg/kg) before HLA-matched sibling allo-SCT in children with sickle cell disease (SCD) is associated with ~85% EFS but is limited by the acute and late effects of BU/CY myeloablative conditioning. Alternatives include reduced toxicity but more immunosuppressive conditioning. We investigated in a prospective single institutional study, the safety and efficacy of a reduced-toxicity conditioning (RTC) regimen of BU 12.8-16 mg/kg, fludarabine 180 mg/m(2), alemtuzumab 54 mg/m(2) (BFA) before HLA-matched sibling donor transplantation in pediatric recipients with symptomatic SCD. Eighteen patients, median age 8.9 years (2.3-20.2), M/F 15/3, 15 sibling BM and 3 sibling cord blood (CB) were transplanted. Mean whole blood and erythroid donor chimerism was 91% and 88%, at days +100 and +365, respectively. Probability of grade II-IV acute GVHD was 17%. Two-year EFS and OS were both 100%. Neurological, pulmonary and cardiovascular function were stable or improved at 2 years. BFA RTC and HLA-matched sibling BM and CB allo-SCT in pediatric recipients result in excellent EFS, long-term donor chimerism, low incidence of GVHD and stable/improved organ function.
authors.affiliation: Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bhatia
authors.affiliation: 1] Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA [2] Department of Biostatistics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Baker
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Geyer
authors.affiliation: Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: K
authors.initials: K
authors.lastname: Radhakrishnan
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: Morris
authors.affiliation: Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Satwani
authors.affiliation: Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: D
authors.initials: D
authors.lastname: George
authors.affiliation: Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Garvin
authors.affiliation: Department of Pediatrics, Wyckoff Heights Medical Center, New York, NY, USA.
authors.forename: G
authors.initials: G
authors.lastname: Del Toro
authors.affiliation: Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zuckerman
authors.affiliation: Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Licursi
authors.affiliation: Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hawks
authors.affiliation: Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: Smilow
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Baxter-Lowe
authors.affiliation: Department of Pathology, Columbia University, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: 1] Department of Pediatrics, New York Medical College, Valhalla, NY, USA [2] Department of Medicine, New York Medical College, Valhalla, NY, USA [3] Department of Pathology, New York Medical College, Valhalla, NY, USA [4] Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA [5] Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000628:therapy*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D035781:Siblings; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine