Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia
Condition: Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Cognitive Side Effects of Cancer Therapy; Long-Term Effects Secondary to Cancer Therapy in Children; Neurotoxicity Syndrome; Psychological Impact of Cancer; Untreated Childhood Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Neurotoxicity Syndromes
Study type: Observational

Summary: 
      This clinical trial is looking at brain function in young patients receiving methotrexate for
      acute lymphoblastic leukemia. Learning about the long-term effects of methotrexate on brain
      function may help doctors plan cancer treatment.
    

Detailed description: 
      OBJECTIVES:

      I. Determine the neuropsychological function in children with acute lymphoblastic leukemia
      treated with either high-dose methotrexate or escalating-dose methotrexate in the absence of
      cranial radiation and nelarabine.

      II. Identify host polymorphisms that predict an increased risk of neurocognitive dysfunction
      or acute neurotoxicity in these patients.

      III. Correlate neuropsychological outcome measures and the occurrence of acute neurotoxicity
      with host polymorphisms in these patients.

      IV. Measure concentrations of 5-methyltetrahydrofolate, homocysteine, Ado,
      S-adenosylmethionine, S-adenosylhomocysteine, and other potentially relevant compounds in
      serum and cerebrospinal fluid during interim maintenance therapy with low- or high-dose
      methotrexate regimens, respectively, and correlate these endpoints with the occurrence of
      acute neurologic toxicity and long-term neurocognitive dysfunction in these patients.

      V. Determine whether or not diffusion tensor imaging will identify areas of selective
      vulnerability in CNS and provide an imaging modality that predicts and/or correlates with
      neuropsychological outcome.

      OUTLINE: This is a prospective, cohort, multicenter study.

      Patients complete neurocognitive tests to assess thinking, memory, attention, and
      concentration. The baseline test is administered during the consolidation phase of
      chemotherapy and further tests are done at 1 year from baseline and 1 year after* the
      completion of study therapy.

      Patients undergo blood and cerebrospinal fluid collection periodically for biomarker,
      genotypic polymorphisms, and pharmacokinetic analysis. Patients undergo MRI diffusion-tensor
      imaging to correlate imaging with neuropsychological outcomes.

      NOTE: * Within 8 months to 24 months after the completion of study therapy for patients on
      AALL0232.
    

Intervention name(s): Cognitive Assessment; Diffusion Tensor Imaging; Laboratory Biomarker Analysis; Pharmacological Study; Psychosocial Assessment and Care
Intervention type(s): Procedure; Procedure; Other; Other; Procedure
Intervention description(s): Ancillary studies; Correlative studies; Correlative studies; Correlative studies; Ancillary studies
Other intervention name(s): DTI; Psychosocial Assessment; Psychosocial Care; Psychosocial Care/Assessment; Psychosocial Studies; Psychosocial Support
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with newly diagnosed acute lymphoblastic leukemia meeting other criteria.
      
Biospecimen description: 
      blood and cerebrospinal fluid