title: A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation.
abstract: Allogeneic hematopoietic cell transplantation (HCT) may produce long-term survival in AML after relapse or primary induction failure (PIF). However, outcomes of HCT performed for AML not in remission are historically poor given high relapse rates and transplant-related mortality. Preliminary studies suggest conditioning with clofarabine and myeloablative busulfan (CloBu4) may exert significant anti-leukemic effects without excessive toxicity in refractory hematologic malignancies. A prospective multicenter phase II trial was conducted to determine the efficacy of CloBu4 for patients proceeding directly to HCT with AML not in remission. Seventy-one patients (median age: 56 years) received CloBu4. At day 30 after HCT, 90% achieved morphologic remission. The incidence of non-relapse mortality and relapse at 2 years was 25% and 55%, respectively. The 2-year overall survival (OS) and event-free survival (EFS) were 26% and 20%, respectively. Patients entering HCT in PIF had significantly greater EFS than those in relapse (34% vs 8%; P<0.01). Multivariate analysis comparing CloBu4 with a contemporaneous cohort (Center for International Blood and Marrow Transplantation Research) of AML not in remission receiving other myeloablative conditioning (n=105) demonstrated similar OS (HR: 1.33, 95% confidence interval: 0.92-1.92; P=0.12). HCT with myeloablative CloBu4 is associated with high early response rates and may produce durable remissions in select patients with AML not in remission.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: J
authors.initials: J
authors.lastname: Magenau
authors.affiliation: Washington University, St. Louis, MO, USA.
authors.forename: P
authors.initials: P
authors.lastname: Westervelt
authors.affiliation: City of Hope, Duarte, CA, USA.|University of Kansas, Westwood, KS, USA.
authors.forename: S
authors.initials: S
authors.lastname: Khaled
authors.affiliation: University of Kansas, Westwood, KS, USA.
authors.forename: J
authors.initials: J
authors.lastname: McGuirk
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: P
authors.initials: P
authors.lastname: Hari
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Eapen
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Becker
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: B
authors.initials: B
authors.lastname: Parkin
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: T
authors.initials: T
authors.lastname: Braun
authors.affiliation: Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: B
authors.initials: B
authors.lastname: Logan
authors.affiliation: Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Vanderbilt University, Nashville, TN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Jagasia
authors.affiliation: Hackensack University Medical Center, Hackensack, NJ, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Rowley
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: D D H
authors.initials: DD
authors.lastname: Kim
authors.affiliation: Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Schechter
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Frey
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Scott
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: T
authors.initials: T
authors.lastname: Churay
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lieland
authors.affiliation: City of Hope, Duarte, CA, USA.|University of Kansas, Westwood, KS, USA.
authors.forename: S
authors.initials: S
authors.lastname: Forman
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mineishi
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D064591:Allografts; D001087:Arabinonucleosides / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage*; D000077866:Clofarabine; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D019172:Transplantation Conditioning
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D000077866:Clofarabine; D002066:Busulfan