Infants with ALL
Infants with ALL are considered to be at high risk for CNS disease. In the past, infants diagnosed before age 2 years were treated with cranial irradiation. As a result, significant deficits in overall intellectual function were noted compared with those in cancer controls. Currently, most ALL treatment protocols do not specify cranial irradiation for infants or very young children. When cranial radiation is avoided, neurodevelopmental outcome improves. One long-term study of infants who received high-dose systemic methotrexate combined with intrathecal cytarabine and methotrexate for CNS leukemia prophylaxis and were tested 3 to 9 years posttreatment showed cognitive function was in the average range.
Neurocognitive abnormalities have been reported in other groups of cancer survivors besides patients with CNS tumors and ALL. In a study of adult survivors of childhood non-CNS cancers (including ALL, n = 5,937), 13% to 21% of survivors had impairment in task efficiency, organization, memory, or emotional regulation. This rate of impairment was approximately 50% higher than that in the sibling comparison. Factors such as diagnosis before age 6 years, female gender, cranial radiation therapy, and hearing impediment were associated with impairment.
Stem cell transplantation
Cognitive and academic consequences of stem cell transplantation in children have also been evaluated. In a report from the St. Jude Children's Research Hospital in which 268 patients were treated with stem cell transplant, minimal risk of late cognitive and academic sequelae was seen. Subgroups of patients were at relatively higher risk, including those undergoing unrelated donor transplantation, receiving total-body irradiation, and developing graft-versus-host disease (GVHD). However, these differences were small relative to differences in premorbid functioning, particularly those associated with socioeconomic status.
Neurocognitive function of pediatric patients with hematologic malignancies who had undergone hematopoietic stem cell transplantation (HSCT) was evaluated before HSCT and then at 1, 3, and 5 years post-HSCT. In this series of 38 patients who had all received intrathecal chemotherapy as part of their treatment, significant declines in visual motor skills and memory test scores were noted within the first year posttransplant. By 3 years posttransplant, there was an improvement in the visual motor development scores and memory scores, but there were new deficits seen in long-term memory scores. By 5 years posttransplant, there were progressive declines in verbal skills, performance skills, and new deficits seen in long-term verbal memory scores. The greatest decline in neurocognitive function occurred in patients who received cranial irradiation either as part of their initial therapy or as part of their HSCT conditioning.