title: Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis.
abstract: BACKGROUND
  The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter.
  
  
  METHODS
  Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given.
  
  
  RESULTS
  Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse.
  
  
  CONCLUSIONS
  This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors.
authors.affiliation: Hematology Department, Hospital Universitario La Fe, Avda. Campanar 21, Valencia, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.forename: Joaquín
authors.initials: J
authors.lastname: Díaz-Mediavilla
authors.forename: Guillermo
authors.initials: G
authors.lastname: Debén
authors.forename: Virginia
authors.initials: V
authors.lastname: Prates
authors.forename: Mar
authors.initials: M
authors.lastname: Tormo
authors.forename: Vicente
authors.initials: V
authors.lastname: Rubio
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Pérez
authors.forename: Isolda
authors.initials: I
authors.lastname: Fernández
authors.forename: Maricruz
authors.initials: M
authors.lastname: Viguria
authors.forename: Chelo
authors.initials: C
authors.lastname: Rayón
authors.forename: José
authors.initials: J
authors.lastname: González
authors.forename: Javier
authors.initials: J
authors.lastname: de la Serna
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
authors.forename: Juan M
authors.initials: JM
authors.lastname: Bergua
authors.forename: Concha
authors.initials: C
authors.lastname: Rivas
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Jose D
authors.initials: JD
authors.lastname: González
authors.forename: Silvia
authors.initials: S
authors.lastname: Negri
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Bob
authors.initials: B
authors.lastname: Lowenberg
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000819:agonists*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D014212:Tretinoin / Q000008:administration & dosage*
chemical_list: D000903:Antibiotics, Antineoplastic; D014212:Tretinoin; D015255:Idarubicin