Pediatric acute lymphoblastic leukemia (ALL) patients treated with chemotherapy alone remain at risk for attention and learning problems that persist after treatment ends, according to St. Jude Children’s Research Hospital investigators. The research appears online this week in the Journal of Clinical Oncology.
ALL is the most common childhood cancer and among the most curable. The study involved the largest and most comprehensive assessment to date of neurocognitive outcomes in pediatric ALL survivors treated with intensive chemotherapy alone rather than in combination with cranial radiation therapy.
This contemporary therapy has helped to reduce treatment-related neurocognitive deficits while maintaining high cure rates. However, although about 90 percent of young ALL patients are alive a decade after their disease was diagnosed; survivors remain at risk for problems with attention and processing speed.
Participants in this study underwent neurocognitive assessments at the beginning, end and two years after finishing contemporary ALL treatment. The research focused on neurocognitive functioning two years after survivors completed therapy, particularly changes that surfaced since the end of therapy.
Two years after therapy, survivors performed as expected for their age on measures of overall intelligence, learning and memory; however, survivors showed a higher risk for attention problems, and parents reported that their children showed increased learning difficulties. The risks were greatest for survivors who were less than 5 years old when their cancer was found and for those who received more intensive chemotherapy. Researchers also found that survivors with attention problems at the end of therapy had lower academic scores two years later.
“These findings provide additional evidence that neurocognitive functioning has improved in survivors of childhood ALL since cranial irradiation was replaced with intensified chemotherapy,” said first and corresponding author Lisa Jacola, Ph.D., a St. Jude Department of Psychology research associate. “But we also show these young people are at an elevated risk for attention problems that have real-world consequences, particularly for learning and school performance.
“Attention is a building block for learning, and in this study attention difficulties predicted academic problems later,” Jacola said. “If we know attention problems seen at the end of therapy continue and contribute to academic problems, then our goal is to intervene earlier to reduce or prevent such difficulties.”
This study built on previous St. Jude research. Participants were enrolled in the St. Jude Total XV protocol (2000 to 2007). The survivors completed standardized tests of overall intelligence, attention, learning and academic performance. Parents and other caregivers also rated survivors’ attention, learning and behavior.
Of the 339 patients eligible for the assessments, 167 completed the process at the end of therapy and two years later. Researchers found no significant differences between survivors who did and did not complete both assessments, suggesting that the results apply to everyone in the study.
“This is an important contribution to the literature because the smaller size and design of previous studies made examining the impact of treatment difficult,” Jacola said. “The findings underscore the need for neurocognitive and academic screening to be included as part of routine survivorship care for all pediatric ALL survivors.”
Meanwhile, research continues to address how ALL treatment affects brain structure and function, particularly for the vast majority of patients who are 3 to 5 years old when their disease occurs. While stimulant medications have been shown to improve survivors’ attention, the medications are not always an option. Computer-based interventions designed like video games are more acceptable to families and are proven to improve working memory in childhood cancer survivors with memory difficulties. More research is needed to determine the best time to intervene to prevent or ease problems.
About this neuroscience and cancer research
The other authors are Kevin Krull, Ching-Hon Pui, Deqing Pei, Cheng Cheng, Wilburn Reddick and senior author Heather Conklin, all of St. Jude.
Funding: Research was funded by NIH/National Cancer Institute, and ALSAC.
Source: Frannie Marmorstein – St. Jude Children’s Research Hospital Image Credit: The image is in the public domain Original Research:Abstract for “Longitudinal Assessment of Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated on a Contemporary Chemotherapy Protocol” by Lisa M. Jacola, Kevin R. Krull, Ching-Hon Pui, Deqing Pei, Cheng Cheng, Wilburn E. Reddick and Heather M. Conklin in Journal of Clinical Oncology. Published online Febraury 8 2016 doi:10.1200/JCO.2015.64.3205
Longitudinal Assessment of Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated on a Contemporary Chemotherapy Protocol
Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) treated with CNS-directed chemotherapy are at risk for neurocognitive deficits. Prospective longitudinal studies are needed to clarify the neurodevelopmental trajectory in this vulnerable population.
Methods Patients enrolled in the St. Jude Total Therapy Study XV, which omitted prophylactic cranial radiation therapy in all patients, completed comprehensive neuropsychological assessments at induction (n = 142), end of maintenance (n = 243), and 2 years after completion of therapy (n = 211). We report on longitudinal change in neurocognitive function and predictors of neurocognitive outcomes 2 years after completing therapy.
Results Neurocognitive function was largely age appropriate 2 years after completing therapy; however, the overall group demonstrated significant attention deficits and a significantly greater frequency of learning problems as compared with national normative data (all P ≤ .005). Higher-intensity CNS-directed chemotherapy conferred elevated risk for difficulties in attention, processing speed, and academics (all P ≤ .01). The rate and direction of change in performance and caregiver-reported attention difficulties differed significantly by age at diagnosis and sex. End-of-therapy attention problems predicted lower academic scores 2 years later, with small to moderate effect sizes (│r│= 0.17 to 0.25, all P ≤ .05).
Conclusion Two years after chemotherapy-only treatment, neurocognitive function is largely age appropriate. Nonetheless, survivors remain at elevated risk for attention problems that impact real-world functioning. Attention problems at the end of therapy predicted decreased academics 2 years later, suggesting an amplified functional impact of discrete neurocognitive difficulties. Age at diagnosis and patient sex may alter neurocognitive development in survivors of childhood ALL treated with chemotherapy-only protocols.
“Longitudinal Assessment of Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated on a Contemporary Chemotherapy Protocol” by Lisa M. Jacola, Kevin R. Krull, Ching-Hon Pui, Deqing Pei, Cheng Cheng, Wilburn E. Reddick and Heather M. Conklin in Journal of Clinical Oncology. Published online Febraury 8 2016 doi:10.1200/JCO.2015.64.3205