title: Phase II Trial of Reduced-Intensity Busulfan/Clofarabine Conditioning with Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Acute Lymphoid Leukemia.
abstract: Clofarabine has potent antileukemia activity and its inclusion in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia could potentially improve outcomes. We conducted a phase II study of busulfan (.8 mg/kg i.v. twice daily on days -5, -4, -3, and -2) with clofarabine (40 mg/m(2) i.v. daily on days -5, -4, -3, and -2) conditioning before allogeneic 8/8 HLA-matched related or unrelated HSCT. The primary endpoint was donor neutrophil engraftment by day +40. Secondary endpoints included nonrelapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS), and overall survival (OS). Thirty-four patients (acute myeloid leukemia [AML], n = 25; myelodysplastic syndromes, n = 5; and acute lymphoid leukemia, n = 4) were enrolled. Day 40+ engraftment with donor chimerism was achieved in 33 of 34 patients with 1 patient dying before count recovery. Day 100 and 1-year NRM were 5.9% (95% confidence interval [CI], 1.0 to 17.4) and 24% (95% CI, 11 to 39), respectively. The 2-year relapse rate was 26% (95% CI, 13 to 42). Cumulative incidences of acute and chronic GVHD were 21% and 44%, respectively. The 2-year PFS was 50% (95% CI, 32 to 65) and OS was 56% (95% CI, 38 to 71). For patients with AML in first complete remission, 2-year PFS and OS were both 82% (95% CI, 55 to 94). RIC with busulfan and clofarabine leads to successful engraftment with acceptable rates of NRM and GVHD.
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Areej
authors.initials: A
authors.lastname: El-Jawahri
authors.affiliation: Division of Computational Biology and Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Shuli
authors.initials: S
authors.lastname: Li
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Ballen
authors.affiliation: Division of Hematological Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Bimalangshu R
authors.initials: BR
authors.lastname: Dey
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jessica
authors.initials: J
authors.lastname: Driscoll
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Chrisa
authors.initials: C
authors.lastname: Hunnewell
authors.affiliation: Division of Hematological Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Steven L
authors.initials: SL
authors.lastname: McAfee
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Cathleen
authors.initials: C
authors.lastname: Poliquin
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Meredith
authors.initials: M
authors.lastname: Saylor
authors.affiliation: Division of Hematological Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Spitzer
authors.affiliation: Division of Hematological Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Edwin
authors.initials: E
authors.lastname: Alyea
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: ychen6@partners.org.
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D001087:Arabinonucleosides / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage*; D002908:Chronic Disease; D000077866:Clofarabine; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy; D019172:Transplantation Conditioning
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D000077866:Clofarabine; D002066:Busulfan
keywords: Acute leukemia; Allogeneic transplant; Busulfan/clofarabine