Cognitive Function Following Stem Cell Transplant in Childhood

Abstract

Source: Phipps S, Rai SN, Leung WH, et al. Cognitive and academic consequences of stem-cell transplantation in children. J Clin Oncol. 2008; 26(12):2027–2033; doi: 10.1200/JCO.2007.13.6135Investigators from St. Jude Children’s Research Hospital sought to prospectively describe cognitive and academic outcomes in survivors after pediatric hematopoietic stem-cell transplantation (SCT).All patients undergoing SCT were eligible for the study, except for those with brain tumors or those for whom English was not their primary language. Patients were administered a battery of neurocognitive tests before transplant and then one, three, and five years later.From 1991 to 1999, 268 patients were enrolled. Of these, 158 who were alive one year after SCT and completed at least one posttransplant assessment comprised the study cohort. Prior to SCT the estimated IQ for the study population was low (93.7).There was a nonsignificant decline of less than two IQ points in study children, with no significant change in achievement tests over the five years following transplant. Age at SCT was not associated with neurocognitive outcome at five years posttransplant.Clinically insignificant declines in IQ were seen for patients transplanted from unrelated donors, those undergoing total body irradiation, and in those with graft versus host disease. Significant differences in outcomes were seen in children from different socioeconomic status (SES) groups, with a 20 IQ point difference between those in the highest and those in the lowest SES groups (P<.001). Dramatic differences in achievement test scores were also seen between the highest and lowest SES groups at all time points measured.The authors conclude that SCT entails minimal risk of late cognitive and academic sequelae and that SES is a much stronger predictor of poor neurocognitive outcome than medical variables. Additional research is necessary to help clinicians identify high-risk patients who may require closer surveillance of neurocognitive function.Dr. Villella has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The findings in this study are good news for pediatric transplant specialists who can now confidently inform families of children undergoing SCT that the risk of neurocognitive sequelae is minimal.This study is noteworthy because it provides prospective data on a large number of patients over the longest follow-up period yet reported. Previous studies evaluating neurocognitive outcomes have been limited by retrospective designs, small sample size, and short durations of follow-up.Several studies, including an earlier report with this same cohort, have shown age <3 years at the time of transplant to be a prominent risk factor for cognitive decline.1 Although age was not found to be a statistically significant predictor in this most recent report, several important observations should be noted.A moderate decline in IQ was seen in patients less than six years old at testing at one year. These patients, though, showed either a plateauing of IQ (for those <3 years old) or a recovery of IQ (for patients 3–5 years old at SCT) at three and five years posttransplant. Complicating these findings is the fact that the youngest subset of patients required at least one change in IQ measurement scales as they aged during the study.The investigators compared data for the subset with no change in IQ scales to the entire cohort and no significant differences were noted. Still, the investigators admitted that an artificial influence of changes in test instrumentation could not be ruled out.Although the findings regarding SES are striking, they should not be surprising. SES is well documented as the most important determinant of cognitive and academic functioning in children.2 Additionally, pretransplant cognitive functioning has previously been shown to be the best predictor of posttransplant cognitive functioning.3Given the findings of this study, close monitoring of neurocognitive functioning following SCT for all pediatric patients appears unnecessary.