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Neurocognitive Problems Linked to Use of Dexamethasone in Survivors of Acute Lymphoblastic Leukemia

TOP - February 2011, Vol 4, No 1 published on February 17, 2011

ORLANDO—Adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with dexamethasone may have greater risk for neurocognitive impairment and poor emotional regulation than patients treated with prednisone, and they exhibited symptoms of physical stress.

A pilot study conducted by Kevin R. Krull, PhD, at St. Jude Children’s Research Hospital in Memphis, Tennessee, and colleagues found an association between the use of dexamethasone during the pediatric patients’ chemotherapy regimen and neurocognitive difficulties as adults.

The researchers used data from the St. Jude Lifetime Cohort Study involving adult survivors of childhood cancers. Patients in the study are at least 10 years from diagnosis.

The 39 participants completing the pilot had received chemotherapy, with no cranial radiation therapy. The team also excluded any patients with Down syndrome or neurologic injury.

Patients underwent neurocognitive evaluations, physical examinations, and laboratory testing after overnight fasting. The dexamethasone group demonstrated significantly lower performance on multiple measures of neurocognitive function, including mathematic problem solving, semantic verbal memory, and cognitive flexibility.

“The dexamethasone group had a significantly higher degree of difficulty regulating emotion, but there was no increase in emotional distress,” Krull said. “They had difficulty expressing emotion but not more depression and anxiety.”

Biological evaluations revealed that patients who had received dexamethasone displayed higher systolic blood pressure than those in the prednisone-exposed group, and their diastolic blood pressure trended higher. Survivors originally treated with dexamethasone also displayed significantly less suppression of cortisol following the dexamethasone-suppression test than people in the prednisone group, which Krull said suggested reactivity within the hypothalamic-pituitary-adrenal axis.

“The body understands [there is stress] but the mind might have adjusted,” Krull said. “We can teach individuals to control, recognize, and address that stress.”

Krull continues to enroll survivors in the study, with plans to bring in 210 more patients, and said that additional follow-up is needed before drawing any definitive conclusions. In the meantime, he suggested that providers not settle for patients’ response that they are fine, but should ask more in-depth questions to ensure that patients are not struggling unnecessarily.

“They have adjusted after more than 30 years of survivorship,” said Krull, explaining that what they now refer to as ‘normal’ has become “a way of life that may be different from their siblings or peer group.”

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Last modified: July 22, 2021