title: Improved outcome in acute myeloid leukemia patients enrolled in clinical trials: A national population-based cohort study of Danish intensive chemotherapy patients.
abstract: Clinical trials are critical to improve AML treatment. It remains, however, unclear if clinical trial participation per se affects prognosis and to what extent the patients selected for trials differ from those of patients receiving intensive therapy off-trial.We conducted a population-based cohort study of newly diagnosed Danish AML patients treated with intensive chemotherapy between 2000-2013. We estimated accrual rates and compared characteristics, complete remission (CR) rates, and relative risks (RRs) of death at 90-day, 1-year, and 3-years in clinical trial patients to patients treated off-trial.Of 867 patients, 58.3% (n = 504) were included in a clinical trial. Accrual rates were similar across age groups (p = 0.55). Patients with poor performance status, comorbidity, therapy-related and secondary AML were less likely to be enrolled in trials. CR rates were 80.2% in trial-patients versus 68.6% in patients treated off- trial. Also, trial-patients had superior survival at 1-year; 72%, vs. 54% (adjusted RR of death 1.28(CI = 1.06-1.54)), and at 3 years; 45% vs. 29% (adjusted RR 1.14(CI = 1.03-1.26)) compared to patients treated off-trial.Despite high accrual rates, patients enrolled in clinical trials had a favorable prognostic profile and a better survival than patients treated off-trial. In conclusion, all trial results should be extrapolated with caution and population-based studies of "real world patients" have a prominent role in examining the prognosis of AML.
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.|Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lene Sofie Granfeldt
authors.initials: LS
authors.lastname: Østgård
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Nørgaard
authors.affiliation: Department of Hematology, The University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Sengeløv
authors.affiliation: Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Medeiros
authors.affiliation: Department of Hematology, The University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Kjeldsen
authors.affiliation: Department of Hematology, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Ulrik Malthe
authors.initials: UM
authors.lastname: Overgaard
authors.affiliation: Department of Hematology, Aalborg University Hospital, Aalborg, Denmark.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Marianne Tang
authors.initials: MT
authors.lastname: Severinsen
authors.affiliation: Department of Hematology, Odense University Hospital, Odense, Denmark.
authors.forename: Claus Werenberg
authors.initials: CW
authors.lastname: Marcher
authors.affiliation: Department of Hematology, Copenhagen University Hospital, Roskilde, Denmark.
authors.forename: Morten Krogh
authors.initials: MK
authors.lastname: Jensen
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jan Maxwell
authors.initials: JM
authors.lastname: Nørgaard
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000188:drug therapy* / Q000401:mortality*; D018579:Patient Selection; D064792:Pragmatic Clinical Trials as Topic / Q000706:statistics & numerical data; D011379:Prognosis; D012074:Remission Induction / Q000379:methods; D061665:Time-to-Treatment / Q000706:statistics & numerical data
chemical_list: D000970:Antineoplastic Agents
keywords: acute myeloid leukemia; chemotherapy; population-based; prognosis; trials