title: Late-occurring neurologic sequelae in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.
abstract: OBJECTIVE
  Children with acute lymphoblastic leukemia (ALL) are often cured, but the therapies they receive may be neurotoxic. Little is known about the incidence and severity of late-occurring neurologic sequelae in ALL survivors. Data were analyzed to determine the incidence of adverse long-term neurologic outcomes and treatment-related risk factors.
  
  
  METHODS
  We analyzed adverse neurologic outcomes that occurred after diagnosis in 4,151 adult survivors of childhood ALL who participated in the Childhood Cancer Survivor Study (CCSS), a retrospective cohort of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. A randomly selected cohort of the survivors' siblings served as a comparison group. Self-reported auditory-vestibular-visual sensory deficits, focal neurologic dysfunction, seizures, and serious headaches were assessed.
  
  
  RESULTS
  The median age at outcome assessment was 20.2 years for survivors. The median follow-up time to death or last survey since ALL diagnosis was 14.1 years. Of the survivors, 64.5% received cranial radiation and 94% received intrathecal chemotherapy. Compared with the sibling cohort, survivors were at elevated risk for late-onset auditory-vestibular-visual sensory deficits (rate ratio [RR], 1.8; 95% CI, 1.5 to 2.2), coordination problems (RR, 4.1; 95% CI, 3.1 to 5.3), motor problems (RR, 5.0; 95% CI, 3.8 to 6.7), seizures (RR, 4.6; 95% CI, 3.4 to 6.2), and headaches (RR, 1.6; 95% CI, 1.4 to 1.7). In multivariable analysis, relapse was the most influential factor that increased risk of late neurologic complications.
  
  
  CONCLUSIONS
  Children treated with regimens that include cranial radiation for ALL and those who suffer a relapse are at increased risk for late-onset neurologic sequelae.
authors.affiliation: UCSF Pediatric Oncology, 505 Parnassus Ave, Box 0106, San Francisco, CA 94143-0106, USA. goldsbyr@peds.ucsf.edu
authors.forename: Robert E
authors.initials: RE
authors.lastname: Goldsby
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Paul C
authors.initials: PC
authors.lastname: Nathan
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bowers
authors.forename: Amanda
authors.initials: A
authors.lastname: Yeaton-Massey
authors.forename: Shannon H
authors.initials: SH
authors.lastname: Raber
authors.forename: Daniel
authors.initials: D
authors.lastname: Hill
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Lonnie
authors.initials: L
authors.lastname: Zeltzer
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Packer
mesh_terms: D000328:Adult; D001259:Ataxia / Q000453:epidemiology; D002648:Child; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D006311:Hearing Disorders / Q000453:epidemiology; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000453:epidemiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D018570:Risk Assessment; D035781:Siblings; D017741:Survivors; D014786:Vision Disorders / Q000453:epidemiology