title: Potential for improved survival with intensification of daunorubicin based induction chemotherapy in acute myeloid leukemia patients who do not receive transplant: A multicenter retrospective study.
abstract: BACKGROUND
  During induction daunorubicin intensification from 45 mg/m(2)/day to 90 mg/m(2)/day has shown improved response and survival rates in AML patients. We retrospectively reviewed outcomes of daunorubicin 60 mg/m(2)/day (DNR60) versus daunorubicin 90 mg/m(2)/day (DNR90) in adult AML patients.
  
  
  METHODS
  Newly diagnosed AML patients ≥18 years who received 7+3 with or without etoposide as frontline therapy from 1/1/2006 to 5/1/2013 were identified. Chi-square and Wilcoxon rank sum tests were used to compare characteristics. Kaplan-Meier curves were estimated for overall survival (OS). Univariate and multivariate Cox proportional hazard regression models were developed to determine independent predictors for survival.
  
  
  RESULTS
  A total of 128 patients were included (DNR90=48 patients, DNR60=80 patients). The estimated 3-year OS rate in the DNR90 group was 56% (95% CI 38-70%), while in the DNR60 group was 34% (95% CI 23-44%). Multivariate analysis (MVA) in non-allotransplanted patients showed that unfavorable cytogenetics and worse performance status were associated with decreased OS while DNR intensification, etoposide use and site were associated with improved OS. In MVA of allotransplanted patients re-induction based on day-14 marrow was associated with worse OS.
  
  
  CONCLUSIONS
  Based on our retrospective study, initial DNR based induction chemotherapy intensification improved OS in non-allotransplanted patients. Prospective studies are needed to confirm this preliminary finding.
authors.affiliation: Division of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA. Electronic address: jreagan@lifespan.org.
authors.forename: John L
authors.initials: JL
authors.lastname: Reagan
authors.affiliation: Division of Hematology and Oncology, Dartmouth Hitchcock Medical Center, Geisel School of Medicine, Lebanon, NH, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sullivan
authors.affiliation: Division of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Winer
authors.affiliation: Division of Hematology and Oncology, Dartmouth Hitchcock Medical Center, Geisel School of Medicine, Lebanon, NH, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Lansigan
authors.affiliation: Division of Pharmacy, Rhode Island Hospital Comprehensive Cancer Center, Providence, RI, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Cardin
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Jorge J
authors.initials: JJ
authors.lastname: Castillo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003630:Daunorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D003630:Daunorubicin
keywords: Acute myeloid leukemia; Acute myeloid leukemia therapy; Chemotherapy; Leukemia