Methylphenidate improves attention, behavior of children surviving acute lymphoblastic leukemia, brain tumors

Children who suffer from behavioral and learning problems after their central nervous systems have been exposed to chemotherapy or radiation appear to benefit from treatment with methylphenidate (MPH), the drug commonly known by the brand name Ritalin®.

These findings, from investigators at St. Jude Children's Research Hospital, are published in the current issue of the Journal of Clinical Oncology (JCO).

The study suggests that MPH can at least temporarily reduce some of the attention and social deficits among survivors of childhood acute lymphoblastic leukemia (ALL) and brain tumors (BTs), the two most common forms of childhood cancer.

Previous studies have shown that these children are likely to develop significant cognitive and behavioral problems compared to their healthy peers, according to Raymond K. Mulhern, Ph.D., chief of St. Jude Behavioral Medicine. Mulhern is lead author of JCO report.

“Our three-week study gave us promising results for children suffering from attention and behavior problems due to their cancer treatments,” Mulhern said. “Our future plans include follow-up evaluations of children who continue MPH treatment for three, six and 12 months. In addition to improvements in learning and behavior, we would also like to know if such treatment results in structural changes in the brain, as hypothesized by other researchers.”

The St. Jude study is the first to examine the ability of two doses of MPH to reduce these problems at home and in the classroom among childhood cancer survivors.

The study included 83 long-term survivors, 40 of whom had survived ALL and 43 of whom survived BTs. The children (47 males and 36 females) were identified as having attention deficits as measured by specific tests and according to both parent and teacher reports. They ranged in age from six months to 14.3 years when they were first diagnosed with cancer, and 6.7 to 17.9 years when they were in the study.

The researchers identified specific children as having attention or behavior problems through various tests, such as the Wechsler scales (IQ tests) and Conner’s Continuous Performance Test (selective and sustained attention, reaction time and level of impulsiveness). Each patient who agreed to participate was then randomly assigned to one of six sequences for a three-week course of treatment with MPH. Each sequence included a low dose of MPH (0.3 mg/kg of body weight), a moderate dose of MPH (0.6 mg/kg of body weight) and a placebo in one of the sequences (e.g., low dose, placebo, high dose). The drug and placebo were administered at school.

The effect of MPH on children in the study was measured by both teachers and parents, who used the Conners’ Rating Scales, and teachers who used the Social Skills Rating System to assess the children. Both teachers and parents reported that, compared to placebo, MPH significantly improved the attention and behavioral problems, although the moderate dose was not consistently more effective than the low dose.

“The treatment of children with ALL and brain tumor shouldn’t end after the cancer has been eradicated,” said Wilburn E. Reddick, Ph.D., director of the diagnostic and signal processing laboratory at St. Jude and co-principal investigator. “This study has shown that follow-up therapy with MPH might help resolve some of the serious side-effects of cancer treatment.”

Other authors of this paper are Raja B. Khan, Stuart Kaplan, Susan Helton, Robbin Christensen, Xiaoping Xiong and Sengjie Wu (St. Jude); Melanie Bonner and Sridharan Gururangan (Duke University, Durham, NC); and Ronald Brown (Temple University, Philadelphia, PA).

This work was supported in part by R01CA078957 from the National Cancer Institute, a Cancer Center Support (CORE) grant from the National Cancer Institute and ALSAC.