Late-occurring neurologic sequelae in adult survivors of childhood acute lymphoblastic leukemia

A report from the childhood cancer survivor study

Robert E. Goldsby, Qi Liu, Paul C. Nathan, Daniel C. Bowers, Amanda Yeaton-Massey, Shannon H. Raber, Daniel Hill, Gregory Armstrong, Yutaka Yasui, Lonnie Zeltzer, Leslie L. Robison, Roger J. Packer

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Abstract

Purpose: 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. Patients and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)324-331
Number of pages8
JournalJournal of Clinical Oncology
Volume28
Issue number2
DOIs
StatePublished - Jan 10 2010

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Nervous System
Survivors
Neoplasms
Headache
Siblings
Seizures
Radiation
Recurrence
Incidence
Neurologic Manifestations
Retrospective Studies
Outcome Assessment (Health Care)
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Late-occurring neurologic sequelae in adult survivors of childhood acute lymphoblastic leukemia : A report from the childhood cancer survivor study. / Goldsby, Robert E.; Liu, Qi; Nathan, Paul C.; Bowers, Daniel C.; Yeaton-Massey, Amanda; Raber, Shannon H.; Hill, Daniel; Armstrong, Gregory; Yasui, Yutaka; Zeltzer, Lonnie; Robison, Leslie L.; Packer, Roger J.

In: Journal of Clinical Oncology, Vol. 28, No. 2, 10.01.2010, p. 324-331.

Research output: Contribution to journalArticle

Goldsby, RE, Liu, Q, Nathan, PC, Bowers, DC, Yeaton-Massey, A, Raber, SH, Hill, D, Armstrong, G, Yasui, Y, Zeltzer, L, Robison, LL & Packer, RJ 2010, 'Late-occurring neurologic sequelae in adult survivors of childhood acute lymphoblastic leukemia: A report from the childhood cancer survivor study', Journal of Clinical Oncology, vol. 28, no. 2, pp. 324-331. https://doi.org/10.1200/JCO.2009.22.5060
Goldsby, Robert E. ; Liu, Qi ; Nathan, Paul C. ; Bowers, Daniel C. ; Yeaton-Massey, Amanda ; Raber, Shannon H. ; Hill, Daniel ; Armstrong, Gregory ; Yasui, Yutaka ; Zeltzer, Lonnie ; Robison, Leslie L. ; Packer, Roger J. / Late-occurring neurologic sequelae in adult survivors of childhood acute lymphoblastic leukemia : A report from the childhood cancer survivor study. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 2. pp. 324-331.
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title = "Late-occurring neurologic sequelae in adult survivors of childhood acute lymphoblastic leukemia: A report from the childhood cancer survivor study",
abstract = "Purpose: 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. Patients and 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. Conclusion: 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.",
author = "Goldsby, {Robert E.} and Qi Liu and Nathan, {Paul C.} and Bowers, {Daniel C.} and Amanda Yeaton-Massey and Raber, {Shannon H.} and Daniel Hill and Gregory Armstrong and Yutaka Yasui and Lonnie Zeltzer and Robison, {Leslie L.} and Packer, {Roger J.}",
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T1 - Late-occurring neurologic sequelae in adult survivors of childhood acute lymphoblastic leukemia

T2 - A report from the childhood cancer survivor study

AU - Goldsby, Robert E.

AU - Liu, Qi

AU - Nathan, Paul C.

AU - Bowers, Daniel C.

AU - Yeaton-Massey, Amanda

AU - Raber, Shannon H.

AU - Hill, Daniel

AU - Armstrong, Gregory

AU - Yasui, Yutaka

AU - Zeltzer, Lonnie

AU - Robison, Leslie L.

AU - Packer, Roger J.

PY - 2010/1/10

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N2 - Purpose: 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. Patients and 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. Conclusion: 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.

AB - Purpose: 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. Patients and 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. Conclusion: 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.

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