Learning Impairments Among Survivors of Childhood Cancer

Children surviving some types of cancer have a higher risk of developing learning problems after cancer treatment than do children who have not had cancer or its treatment. Cancer treatment may cause problems with learning, attention, and memory. The purpose of this study is to identify brain changes that may underlie learning problems in cancer survivors and investigate whether methylphenidate (a stimulant medication) may reduce these problems. Subjects who have had treatment for acute lymphoblastic leukemia (ALL) or a brain tumor will be asked to take part in this research study. Siblings of some subjects will also be asked to take part, so that their results can be compared with those of children who have had cancer treatment. We hypothesize that children receiving more aggressive therapy will have lower white matter brain volumes and these volumes will be significantly lower than age-matched siblings. We also hypothesize that children who take methylphenidate will show improvements on teacher and parent report measures of attention and social skills.

Sex

All

Minimum age

6 Years

Maximum age

18 Years

Inclusion Criteria:

* Age: 6 to 18 years old.
* Active subject at St. Jude Children's Research Hospital, or is an age-matched sibling control subject.
* If a subject, received treatment for brain tumor or ALL with either radiation therapy and/or chemotherapy directed at the brain.
* If a subject, at least 12 months post-completion of antineoplastic therapies
* If a subject, no evidence of malignancy, or continuously stable disease since completion of therapy
* English as a primary language
* Informed consent

Exclusion Criteria:

* Glaucoma
* Patient or immediate family member with a history of Tourette's syndrome
* Current antidepressant, anxiolytic, antipsychotic or stimulant therapy
* History of substance abuse
* Recent history of uncontrolled seizures
* Uncorrected hypothyroidism
* Previously or currently randomized on COGRM1 intervention arm
* Previously diagnosed with ADHD, or, if a patient, diagnosed with ADHD prior to diagnosis of malignancy

• BACKGROUNDMulhern RK, Khan RB, Kaplan S, Helton S, Christensen R, Bonner M, Brown R, Xiong X, Wu S, Gururangan S, Reddick WE. Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer. J Clin Oncol. 2004 Dec 1;22(23):4795-803. doi: 10.1200/JCO.2004.04.128. PMID 15570081
• BACKGROUNDReddick WE, Shan ZY, Glass JO, Helton S, Xiong X, Wu S, Bonner MJ, Howard SC, Christensen R, Khan RB, Pui CH, Mulhern RK. Smaller white-matter volumes are associated with larger deficits in attention and learning among long-term survivors of acute lymphoblastic leukemia. Cancer. 2006 Feb 15;106(4):941-9. doi: 10.1002/cncr.21679. PMID 16411228
• BACKGROUNDConklin HM, Khan RB, Reddick WE, Helton S, Brown R, Howard SC, Bonner M, Christensen R, Wu S, Xiong X, Mulhern RK. Acute neurocognitive response to methylphenidate among survivors of childhood cancer: a randomized, double-blind, cross-over trial. J Pediatr Psychol. 2007 Oct;32(9):1127-39. doi: 10.1093/jpepsy/jsm045. Epub 2007 Jun 14. PMID 17569711
• BACKGROUNDReeves CB, Palmer S, Gross AM, Simonian SJ, Taylor L, Willingham E, Mulhern RK. Brief report: sluggish cognitive tempo among pediatric survivors of acute lymphoblastic leukemia. J Pediatr Psychol. 2007 Oct;32(9):1050-4. doi: 10.1093/jpepsy/jsm063. Epub 2007 Oct 12. PMID 17933846
• DERIVEDConklin HM, Lawford J, Jasper BW, Morris EB, Howard SC, Ogg SW, Wu S, Xiong X, Khan RB. Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial. Pediatrics. 2009 Jul;124(1):226-33. doi: 10.1542/peds.2008-1855. PMID 19564304