title: Epidemiology and Clinical Significance of Secondary and Therapy-Related Acute Myeloid Leukemia: A National Population-Based Cohort Study.
abstract: OBJECTIVE
  Secondary and therapy-related acute myeloid leukemia (sAML and tAML, respectively) remain therapeutic challenges. Still, it is unclear whether their inferior outcome compared with de novo acute myeloid leukemia (AML) varies as a result of previous hematologic disease or can be explained by differences in karyotype and/or age.
  
  
  METHODS
  In a Danish national population-based study of 3,055 unselected patients with AML diagnosed from 2000 to 2013, we compared the frequencies and characteristics of tAML, myelodysplastic syndrome (MDS) -sAML, and non-MDS-sAML (chronic myelomonocytic leukemia and myeloproliferative neoplasia) versus de novo AML. Limited to intensive therapy patients, we compared chance of complete remission by logistic regression analysis and used a pseudo-value approach to compare relative risk (RR) of death at 90 days, 1 year, and 3 years, overall and stratified by age and karyotype. Results were given crude and adjusted with 95% CIs.
  
  
  RESULTS
  Overall, frequencies of sAML and tAML were 19.8% and 6.6%, respectively. sAML, but not tAML, was associated with low likelihood of receiving intensive treatment. Among intensive therapy patients (n = 1,567), antecedent myeloid disorder or prior cytotoxic exposure was associated with decreased complete remission rates and inferior survival (3-year adjusted RR for MDS-sAML, non-MDS-sAML, and tAML: RR, 1.14; 95% CI, 1.02 to 1.32; RR, 1.27; 95% CI, 1.16 to 1.34; and RR, 1.16; 95% CI, 1.03 to 1.32, respectively) compared with de novo AML. Among patients ≥ 60 years old and patients with adverse karyotype, previous MDS or tAML did not impact overall outcomes, whereas non-MDS-sAML was associated with inferior survival across age and cytogenetic risk groups (adverse risk cytogenetics: 1-year adjusted RR, 1.47; 95% CI, 1.23 to 1.76; patients ≥ 60 years old: 1-year adjusted RR, 1.31; 95% CI, 1.06 to 1.61).
  
  
  CONCLUSIONS
  Our results support that de novo AML, sAML, and tAML are biologically and prognostically distinct subtypes of AML. Patients with non-MDS-sAML have dismal outcomes, independent of age and cytogenetics. Previous myeloid disorder, age, and cytogenetics are crucial determinants of outcomes and should be integrated in treatment recommendations for these patients.
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. lenoestg@rm.dk.
authors: Lene Sofie
authors: LS
authors: Granfeldt Østgård
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
authors: Bruno C
authors: BC
authors: Medeiros
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
authors: Henrik
authors: H
authors: Sengeløv
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
authors: Mette
authors: M
authors: Nørgaard
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
authors: Mette Klarskov
authors: MK
authors: Andersen
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
authors: Inge Høgh
authors: IH
authors: Dufva
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
authors: Lone Smidstrup
authors: LS
authors: Friis
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
authors: Eigil
authors: E
authors: Kjeldsen
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
authors: Claus Werenberg
authors: CW
authors: Marcher
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
authors: Birgitte
authors: B
authors: Preiss
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
authors: Marianne
authors: M
authors: Severinsen
authors: Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.
authors: Jan Maxwell
authors: JM
authors: Nørgaard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D006402:Hematologic Diseases / Q000150:complications / Q000188:drug therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000628:therapy; D009196:Myeloproliferative Disorders / Q000453:epidemiology / Q000628:therapy; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology; D011379:Prognosis; D012042:Registries; D012044:Regression Analysis; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents