Late-occurring neurologic sequelae in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.
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.
Goldsby
Robert E
RE
UCSF Pediatric Oncology, 505 Parnassus Ave, Box 0106, San Francisco, CA 94143-0106, USA. goldsbyr@peds.ucsf.edu
Liu
Qi
Q
Nathan
Paul C
PC
Bowers
Daniel C
DC
Yeaton-Massey
Amanda
A
Raber
Shannon H
SH
Hill
Daniel
D
Armstrong
Gregory T
GT
Yasui
Yutaka
Y
Zeltzer
Lonnie
L
Robison
Leslie L
LL
Packer
Roger J
RJ
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