title: Variations in erythropoiesis-stimulating agent administration in transfusion-dependent myelodysplastic syndromes impact response.
abstract: BACKGROUND
  Erythropoiesis-stimulating agents (ESAs) reduce red blood cell (RBC) transfusions in approximately 40% of patients with myelodysplastic syndrome (MDS) in clinical trials. We studied the association of timing of ESA initiation, agent (epoetin alfa, darbepoetin) and number of weeks of ESA use with response in MDS patients in routine practice.
  
  
  METHODS
  Patients diagnosed with MDS from 2001 to 2005 were identified in the Surveillance Epidemiology and End Results-Medicare linked database. The study cohort consisted of patients with new-onset transfusion dependence (TD). All patients received an ESA at least once during the study period, which began the week that criteria for TD were met and continued until transfusion independence (TI). Kaplan-Meier statistics and Cox Proportional Hazard models were used to assess relationships between time to ESA initiation, agent and number of weeks of ESA use and TI attainment.
  
  
  RESULTS
  Of 610 TD patients treated with ESAs, 210 (34.4%) achieved TI. Median time from ESA initiation to TI was 13 weeks. Shorter time from TD to ESA initiation and use of darbepoetin were associated with higher probability of achieving TI. The probability of achieving TI decreased beyond 8 weeks of treatment, and was very low beyond 16 weeks (8-15 weeks: HR=0.64, 16-31 weeks: HR=0.25, 32+ weeks HR=0.10).
  
  
  CONCLUSIONS
  In this observational, population-based study, variations in ESA administration impacted response in transfusion-dependent MDS patients, with higher response rates with early administration and use of darbepoetin, and low response likelihood in non-responders beyond 16 weeks of therapy.
authors: University of Maryland Marlene and Stewart Greenebaum Cancer Center and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: vduong@umm.edu.
authors: Vu H
authors: VH
authors: Duong
authors: University of Maryland Marlene and Stewart Greenebaum Cancer Center and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Maria R
authors: MR
authors: Baer
authors: Pharmaceutical Health Services Research Department, University of Maryland School of Pharmacy, Baltimore, MD, USA.
authors: Franklin
authors: F
authors: Hendrick
authors: Pharmaceutical Health Services Research Department, University of Maryland School of Pharmacy, Baltimore, MD, USA.
authors: Sheila R
authors: SR
authors: Weiss
authors: Pharmaceutical Health Services Research Department, University of Maryland School of Pharmacy, Baltimore, MD, USA.
authors: Masayo
authors: M
authors: Sato
authors: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors: Amer M
authors: AM
authors: Zeidan
authors: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors: Steven D
authors: SD
authors: Gore
authors: Agency for Healthcare Research and Quality, Rockville, MD, USA.
authors: Amy J
authors: AJ
authors: Davidoff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001803:Blood Transfusion; D000068256:Darbepoetin alfa; D016208:Databases, Factual; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006397:Hematinics / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012189:Retrospective Studies
chemical_list: D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa
keywords: Anemia; Comparative effectiveness; Erythropoiesis-stimulating agents; Myelodysplastic syndromes