title: Therapy-related myeloid neoplasms in patients with acute promyelocytic leukemia treated with all-trans-retinoic Acid and anthracycline-based chemotherapy.
abstract: OBJECTIVE
  We analyzed the incidence, risk factors, and outcome of therapy-related myeloid neoplasms (t-MNs) in patients with acute promyelocytic leukemia (APL) in first complete remission (CR).
  
  
  METHODS
  From 1996 to 2008, 1,025 patients with APL were enrolled onto three sequential trials (LPA96, LPA99, and LPA2005) of the Programa Español para el Tratamiento de Enfermedades Hematológicas and received induction and consolidation therapy with all-trans-retinoic acid (ATRA) and anthracycline-based chemotherapy.
  
  
  RESULTS
  Seventeen of 918 patients who achieved CR developed t-MN (10 with < 20% and seven with > or = 20% of bone marrow blasts) after a median of 43 months from CR. Partial and complete deletions of chromosomes 5 and 7 (nine patients) and 11q23 rearrangements (three patients) were the most common cytogenetic abnormalities. Overall, the 6-year cumulative incidence of t-MN was 2.2%, whereas in low-, intermediate-, and high-risk patients, the 6-year incidence was 5.2%, 2.1%, and 0%, respectively. Multivariate analysis identified age more than 35 years and lower relapse risk score as independent prognostic factors for t-MN. The median overall survival time after t-MN was 10 months.
  
  
  CONCLUSIONS
  t-MN is a relatively infrequent, long-term, and severe complication after first-line treatment for APL with ATRA and anthracycline-based regimens. Therapeutic strategies to reduce the incidence of t-MN are warranted.
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.forename: José D
authors.initials: JD
authors.lastname: González
authors.forename: José
authors.initials: J
authors.lastname: González
authors.forename: Chelo
authors.initials: C
authors.lastname: Rayón
authors.forename: Elena
authors.initials: E
authors.lastname: de Lisa
authors.forename: Maria L
authors.initials: ML
authors.lastname: Amigo
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: María J
authors.initials: MJ
authors.lastname: Peñarrubia
authors.forename: Manuel
authors.initials: M
authors.lastname: Pérez-Encinas
authors.forename: Juan
authors.initials: J
authors.lastname: Bergua
authors.forename: Guillermo
authors.initials: G
authors.lastname: Debén
authors.forename: María J
authors.initials: MJ
authors.lastname: Sayas
authors.forename: Javier
authors.initials: J
authors.lastname: de la Serna
authors.forename: Josep M
authors.initials: JM
authors.lastname: Ribera
authors.forename: Javier
authors.initials: J
authors.lastname: Bueno
authors.forename: Gustavo
authors.initials: G
authors.lastname: Milone
authors.forename: Concha
authors.initials: C
authors.lastname: Rivas
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Miguel
authors.initials: M
authors.lastname: Sanz
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D019046:Bone Marrow Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000453:epidemiology; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D018943:Anthracyclines; D014212:Tretinoin