title: A novel clofarabine bridge strategy facilitates allogeneic transplantation in patients with relapsed/refractory leukemia and high-risk myelodysplastic syndromes.
abstract: Patients with relapsed/refractory leukemias or advanced myelodysplastic syndrome (MDS) fare poorly following allogeneic hematopoietic cell transplant (HCT). We report prospective phase II study results of 29 patients given clofarabine 30 mg/m(2)/day i.v. × 5 days followed immediately by HCT conditioning while at the cytopenic nadir. A total of 15/29 patients (52%) were cytoreduced according to pre-defined criteria (cellularity <20% and blasts <10%). Marrow cellularity (P<0.0001) and blast% (P=0.03) were reduced. Toxicities were acceptable, with transient hyperbilirubinemia (48%) and gr3-4 infections (10%). In all, 28/29 proceeded to transplant; 27 received ATG or alemtuzumab. Post HCT, 180 day non-relapse mortality (NRM) was 7% (95% confidence interval (CI): 1-21), relapse was 29% (95% CI: 13-46) and OS was 71% (95% CI: 51-85), comparing favorably to published data for high-risk patients. Two-year graft vs host disease incidence was 40% (95% CI: 21-58) and 2 year OS was 31% (95% CI: 14-48). Disease at the nadir correlated with inferior OS after HCT (HR=1.22 for each 10% marrow blasts, 95% CI: 1.02-1.46). For AML/MDS patients, there was a suggestion that successful cytoreduction increased PFS (330 vs 171 days, P=0.3) and OS (375 vs 195 days, P=0.31). Clofarabine used as a bridge to HCT reduces disease burden, is well tolerated, and permits high-risk patients to undergo HCT with acceptable NRM. Late relapses are common; thus, additional strategies should be pursued. NCT-00724009.
authors.affiliation: 1] Department of Blood and Marrow Transplant, H Lee Moffitt Cancer Center, Tampa, FL, USA [2] Department of Oncologic Sciences, University of South Florida, Tampa, FL, USA.
authors.forename: F
authors.initials: F
authors.lastname: Locke
authors.forename: R
authors.initials: R
authors.lastname: Agarwal
authors.forename: R
authors.initials: R
authors.lastname: Kunnavakkam
authors.forename: K
authors.initials: K
authors.lastname: van Besien
authors.forename: R A
authors.initials: RA
authors.lastname: Larson
authors.forename: O
authors.initials: O
authors.lastname: Odenike
authors.forename: L A
authors.initials: LA
authors.lastname: Godley
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: M M
authors.initials: MM
authors.lastname: Le Beau
authors.forename: S
authors.initials: S
authors.lastname: Gurbuxani
authors.forename: M J
authors.initials: MJ
authors.lastname: Thirman
authors.forename: D
authors.initials: D
authors.lastname: Sipkins
authors.forename: C
authors.initials: C
authors.lastname: White
authors.forename: A
authors.initials: A
authors.lastname: Artz
authors.forename: W
authors.initials: W
authors.lastname: Stock
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D001087:Arabinonucleosides / Q000008:administration & dosage*; D000077866:Clofarabine; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000601:surgery / Q000628:therapy; D011446:Prospective Studies; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D000077866:Clofarabine