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J Clin Oncol. 2017 Aug 10;35(23):2700-2707. doi: 10.1200/JCO.2016.71.7587. Epub 2017 Jul 3.

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.

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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.


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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