Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia

A report from the St jude lifetime cohort study

Kevin R. Krull, Tara M. Brinkman, Chenghong Li, Gregory Armstrong, Kirsten K. Ness, Deo Kumar Srivastava, James G. Gurney, Cara Kimberg, Matthew J. Krasin, Ching Hon Pui, Leslie L. Robison, Melissa M. Hudson

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Abstract

Purpose To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL). Patients and Methods Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age < 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion. Results Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment. Conclusion This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature. J Clin Oncol 31:4407-4415.

Original languageEnglish (US)
Pages (from-to)4407-4415
Number of pages9
JournalJournal of Clinical Oncology
Volume31
Issue number35
DOIs
StatePublished - Dec 10 2013

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Survivors
Cohort Studies
Radiotherapy
Executive Function
Therapeutics
Drug Therapy
Unemployment
Intelligence
Dexamethasone
Medical Records
Survival
Health
Brain
Research

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia : A report from the St jude lifetime cohort study. / Krull, Kevin R.; Brinkman, Tara M.; Li, Chenghong; Armstrong, Gregory; Ness, Kirsten K.; Kumar Srivastava, Deo; Gurney, James G.; Kimberg, Cara; Krasin, Matthew J.; Pui, Ching Hon; Robison, Leslie L.; Hudson, Melissa M.

In: Journal of Clinical Oncology, Vol. 31, No. 35, 10.12.2013, p. 4407-4415.

Research output: Contribution to journalArticle

Krull, KR, Brinkman, TM, Li, C, Armstrong, G, Ness, KK, Kumar Srivastava, D, Gurney, JG, Kimberg, C, Krasin, MJ, Pui, CH, Robison, LL & Hudson, MM 2013, 'Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: A report from the St jude lifetime cohort study', Journal of Clinical Oncology, vol. 31, no. 35, pp. 4407-4415. https://doi.org/10.1200/JCO.2012.48.2315
Krull, Kevin R. ; Brinkman, Tara M. ; Li, Chenghong ; Armstrong, Gregory ; Ness, Kirsten K. ; Kumar Srivastava, Deo ; Gurney, James G. ; Kimberg, Cara ; Krasin, Matthew J. ; Pui, Ching Hon ; Robison, Leslie L. ; Hudson, Melissa M. / Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia : A report from the St jude lifetime cohort study. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 35. pp. 4407-4415.
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title = "Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: A report from the St jude lifetime cohort study",
abstract = "Purpose To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL). Patients and Methods Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age < 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8{\%}) agreed to participate, and 567 (76.8{\%}) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion. Results Impairment rates across neurocognitive domains ranged from 28.6{\%} to 58.9{\%}, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95{\%} CI, 1.11 to 4.03) and executive function (RR, 2.42; 95{\%} CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5{\%} (RR, 1.05; 95{\%} CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment. Conclusion This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature. J Clin Oncol 31:4407-4415.",
author = "Krull, {Kevin R.} and Brinkman, {Tara M.} and Chenghong Li and Gregory Armstrong and Ness, {Kirsten K.} and {Kumar Srivastava}, Deo and Gurney, {James G.} and Cara Kimberg and Krasin, {Matthew J.} and Pui, {Ching Hon} and Robison, {Leslie L.} and Hudson, {Melissa M.}",
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T1 - Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia

T2 - A report from the St jude lifetime cohort study

AU - Krull, Kevin R.

AU - Brinkman, Tara M.

AU - Li, Chenghong

AU - Armstrong, Gregory

AU - Ness, Kirsten K.

AU - Kumar Srivastava, Deo

AU - Gurney, James G.

AU - Kimberg, Cara

AU - Krasin, Matthew J.

AU - Pui, Ching Hon

AU - Robison, Leslie L.

AU - Hudson, Melissa M.

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N2 - Purpose To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL). Patients and Methods Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age < 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion. Results Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment. Conclusion This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature. J Clin Oncol 31:4407-4415.

AB - Purpose To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL). Patients and Methods Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age < 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion. Results Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment. Conclusion This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature. J Clin Oncol 31:4407-4415.

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