Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report From the Children's Oncology Group

Kristina K Hardy; Leanne Embry; John A Kairalla; Shanjun Helian; Meenakshi Devidas; Daniel Armstrong; Stephen Hunger; William L Carroll; Eric Larsen; Elizabeth A Raetz; Mignon L Loh; Wenjian Yang; Mary V Relling; Robert B Noll; Naomi Winick

doi:10.1200/JCO.2016.71.7587

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Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report From the Children's Oncology Group

Journal article

Open access

Peer reviewed

Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report From the Children's Oncology Group

Kristina K Hardy, Leanne Embry, John A Kairalla, Shanjun Helian, Meenakshi Devidas, Daniel Armstrong, Stephen Hunger, William L Carroll, Eric Larsen, Elizabeth A Raetz, …

Journal of clinical oncology, Vol.35(23), pp.2700-2707

2017-08-10

DOI: https://doi.org/10.1200/JCO.2016.71.7587

PMCID: PMC5549456

PMID: 28671857

Abstract

Adrenal Cortex Hormones - administration & dosage

Adult Survivors of Child Adverse Events

Age Factors

Antineoplastic Combined Chemotherapy Protocols - therapeutic use

Asparaginase - administration & dosage

Child

Cognition - drug effects

Dexamethasone - administration & dosage

Female

Humans

Insurance, Health

Intelligence - drug effects

Leucovorin - administration & dosage

Male

Medicaid

Memory, Short-Term - drug effects

Methotrexate - administration & dosage

Polyethylene Glycols - administration & dosage

Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy

Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - psychology

Prednisone - administration & dosage

Reaction Time - drug effects

United States

Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that are associated with treatment, individual, and environmental factors. This study examined the impact of different methotrexate (MTX) and corticosteroid treatment strategies on neurocognitive functioning in children with high-risk B-lineage ALL. Methods Participants were randomly assigned to receive high-dose MTX with leucovorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue. Patients were also randomly assigned to corticosteroid therapy that included either dexamethasone or prednisone. A neurocognitive evaluation of intellectual functioning (IQ), working memory, and processing speed (PS) was conducted 8 to 24 months after treatment completion (n = 192). Results The method of MTX delivery and corticosteroid assignment were unrelated to differences in neurocognitive outcomes after controlling for ethnicity, race, age, gender, insurance status, and time off treatment; however, survivors who were age < 10 years at diagnosis (n = 89) had significantly lower estimated IQ ( P < .001) and PS scores ( P = .02) compared with participants age ≥ 10 years. In addition, participants who were covered by US public health insurance had estimated IQs that were significantly lower ( P < .001) than those with US private or military insurance. Conclusion Children with high-risk B-lineage ALL who were age < 10 years at diagnosis are at risk for deficits in IQ and PS in the absence of cranial radiation, regardless of MTX delivery or corticosteroid type. These data may serve as a basis for developing screening protocols to identify children who are at high risk for deficits so that early intervention can be initiated to mitigate the impact of therapy on neurocognitive outcomes.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.112 Palliative Care; 1.112.1459 Childhood Cancer
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report From the Children's Oncology Group
Creators: Kristina K Hardy - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Leanne Embry - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
John A Kairalla - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Shanjun Helian - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Meenakshi Devidas - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Daniel Armstrong - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Stephen Hunger - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
William L Carroll - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Eric Larsen - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Elizabeth A Raetz - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Mignon L Loh - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Wenjian Yang - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Mary V Relling - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Robert B Noll - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Naomi Winick - Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN
Publication Details: Journal of clinical oncology, Vol.35(23), pp.2700-2707
Grant note: P30 CA021765 / NCI NIH HHS U10 CA180899 / NCI NIH HHS U10 CA098413 / NCI NIH HHS P50 GM115279 / NIGMS NIH HHS U10 CA180886 / NCI NIH HHS U10 CA098543 / NCI NIH HHS
Academic Unit: Leadership Department; Miller School of Medicine; UMMG Dept of Pediatrics - Mailman Center for Child Development
Language: English
Resource Type: Journal article
PMID: 28671857
PMCID: PMC5549456
Record Identifier: 991031614395802976