Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis

Abstract

• Children treated for ALL without cranial radiation display significant IQ deficits of 6 to 8 points compared with healthy controls.• Moderate deficits occur in other neurocognitive domains including working memory, information processing speed, and fine motor functioning.Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with 5-year survival rates of ∼90% even after largely eliminating cranial radiation. This meta-analysis assesses the long-term neurocognitive functioning after chemotherapy-only regimens among survivors of childhood ALL. We conducted a systematic review to identify studies that evaluated long-term neurocognitive functioning following treatment of ALL by searching MEDLINE/PubMed, Database of Abstracts of Reviews of Effects, and secondary sources. Studies were included if ALL survivors were in continuous first remission, did not receive any radiation, were at least ‡2 years off therapy or ‡5 years since diagnosis, and were compared with a healthy control group. Weighted mean differences with 95% confidence intervals (CIs) were calculated. Ten nonexperimental studies met all eligibility criteria and included 509 patients and 555 controls. Meta-analysis demonstrated statistically significant moderate impairment across multiple neurocognitive domains evaluated, with intelligence most affected. Significant differences in standard deviation (SD) scores were found for Full Scale intelligence quotient (IQ) (20.52 SD; 95% CI, 20.68 to 20.37), Verbal IQ (20.54 SD; 95% CI, 20.69 to 20.40), and Performance IQ (20.41 SD; 95% CI, 20.56 to 20.27); these SD scores correspond to changes in IQ of 6 to 8 points. Working memory, information processing speed, and fine motor domains were moderately, but statistically significantly, impaired. Meta-analysis of ALL survivors treated without cranial radiation demonstrated significant impairment in IQ and other neurocognitive domains. Patients and their families should be informed about these potential negative effects to encourage surveillance and educational planning. Both preventive and intervention strategies are needed. (Blood. 2015;126(3):346-353) IntroductionAcute lymphoblastic leukemia (ALL) is the most common malignancy in children, accounting for 18% of all cancers and 74% of all leukemias.1 As a result of improvements in treatment and supportive care over recent decades, the current 5-year relative survival rate is 89% for children diagnosed with ALL before age 20 years 1 and exceeds 93% for children with standard risk features diagnosed before age 10 years.2 Because the vast majority of children with ALL are expected to survive their disease, it is important to understand the long-term burden of therapy.Neurocognitive and psychological difficulties as a result of chemotherapy have been documented in survivors of adult cancer across a variety of cancer types.3 However, most pediatric studies have focused on children with brain tumors or central nervous system (CNS)-directed radiation treatment. 4 Although the deleterious neurocognitive ...

Progress and Prospects in Pediatric Leukemia

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