title: G-CSF priming, clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm.
abstract: Prior study of the combination of clofarabine and high dose cytarabine with granulocyte colony-stimulating factor (G-CSF) priming (GCLAC) in relapsed or refractory acute myeloid leukemia resulted in a 46% rate of complete remission despite unfavorable risk cytogenetics. A multivariate analysis demonstrated that the remission rate and survival with GCLAC were superior to FLAG (fludarabine, cytarabine, G-CSF) in the relapsed setting. We therefore initiated a study of the GCLAC regimen in the upfront setting in a multicenter trial. The objectives were to evaluate the rates of complete remission (CR), overall and relapse-free survival (OS and RFS), and toxicity of GCLAC. Clofarabine was administered at 30 mg m(-2) day(-1) × 5 and cytarabine at 2 g m(-2) day(-1) × 5 after G-CSF priming in 50 newly-diagnosed patients ages 18-64 with AML or advanced myelodysplastic syndrome (MDS) or advanced myeloproliferative neoplasm (MPN). Responses were assessed in the different cytogenetic risk groups and in patients with antecedent hematologic disorder. The overall CR rate was 76% (95% confidence interval [CI] 64-88%) and the CR + CRp (CR with incomplete platelet count recovery) was 82% (95% CI 71-93%). The CR rate was 100% for patients with favorable, 84% for those with intermediate, and 62% for those with unfavorable risk cytogenetics. For patients with an antecedent hematologic disorder (AHD), the CR rate was 65%, compared to 85% for those without an AHD. The 60 day mortality was 2%. Thus, front line GCLAC is a well-tolerated, effective induction regimen for AML and advanced myelodysplastic or myeloproliferative disorders.
authors.affiliation: Division of Hematology, Department of Medicine, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Becker
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Medeiros
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Stein
authors.forename: Megan
authors.initials: M
authors.lastname: Othus
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Bart L
authors.initials: BL
authors.lastname: Scott
authors.forename: Paul C
authors.initials: PC
authors.lastname: Hendrie
authors.forename: Kelda M
authors.initials: KM
authors.lastname: Gardner
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.forename: Roland B
authors.initials: RB
authors.lastname: Walter
authors.forename: Cynthia
authors.initials: C
authors.lastname: Parks
authors.forename: Brent L
authors.initials: BL
authors.lastname: Wood
authors.forename: Janis L
authors.initials: JL
authors.lastname: Abkowitz
authors.forename: Elihu H
authors.initials: EH
authors.lastname: Estey
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077866:Clofarabine; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D009196:Myeloproliferative Disorders / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D055815:Young Adult
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D000077866:Clofarabine