title: Longitudinal Assessment of Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated on a Contemporary Chemotherapy Protocol.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors: All authors: St. Jude Children's Research Hospital, Memphis TN. lisa.jacola@stjude.org.
authors: Lisa M
authors: LM
authors: Jacola
authors: All authors: St. Jude Children's Research Hospital, Memphis TN.
authors: Kevin R
authors: KR
authors: Krull
authors: All authors: St. Jude Children's Research Hospital, Memphis TN.
authors: Ching-Hon
authors: CH
authors: Pui
authors: All authors: St. Jude Children's Research Hospital, Memphis TN.
authors: Deqing
authors: D
authors: Pei
authors: All authors: St. Jude Children's Research Hospital, Memphis TN.
authors: Cheng
authors: C
authors: Cheng
authors: All authors: St. Jude Children's Research Hospital, Memphis TN.
authors: Wilburn E
authors: WE
authors: Reddick
authors: All authors: St. Jude Children's Research Hospital, Memphis TN.
authors: Heather M
authors: HM
authors: Conklin
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001288:Attention / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects*; D005260:Female; D006801:Humans; D007223:Infant; D007360:Intelligence / Q000187:drug effects; D007361:Intelligence Tests; D007858:Learning / Q000187:drug effects; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011595:Psychomotor Agitation / Q000453:epidemiology; D017741:Survivors; D013647:Task Performance and Analysis; D055815:Young Adult