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Poor neurocognitive outcomes observed in survivors of childhood Hodgkin’s lymphoma
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More than half of adult survivors of childhood Hodgkin’s lymphoma developed leukoencephalopathy, according to study results.
“These results suggest that adult long-term survivors of childhood [Hodgkin’s lymphoma] are at risk for neurocognitive impairment, which is associated with radiologic indices suggestive of reduced brain integrity and which occurs in the presence of symptoms of cardiopulmonary dysfunction,” Kevin R. Krull, PhD, of the departments of epidemiology and cancer control psychology at St. Jude Children’s Research Hospital, and colleagues wrote.
Researchers from several sites in the United States conducted the study to examine neurocognitive and brain imaging outcomes among 62 adult survivors of childhood Hodgkin’s lymphoma. The mean age at diagnosis was 15.1 years (standard deviation [SD], 3.3 years) and the mean age at analysis was 42.2 years (SD, 4.77).
The study included 38 patients who had been treated with high-dose (≥30 Gy) thoracic radiation and 24 patients who had received a lower dose of thoracic radiation (<30 Gy) combined with anthracycline.
Patients underwent neurocognitive evaluation, brain MRI, echocardiograms, pulmonary function tests and physical examinations.
When compared with age-adjusted normal levels among the US population, adult survivors of Hodgkin’s lymphoma demonstrated lower performance on several neurocognitive measures, including sustained attention (P=.004), short-term memory (P=.001), long-term memory (P=.006), working memory (P<.001), naming speed (P<.001) and cognitive fluency (P=.007).
Fifty-three percent of survivors had leukoencephalopathy and 37% had evidence of cerebrovascular injury, according to MRI results.
Krull and colleagues observed a link between higher thoracic radiation dose and impaired diastolic function (E/E’; ratio of peak mitral flow velocity of early rapid filling [E] to early diastolic velocity of the mitral annulus [E’]; P=.003). Impaired pulmonary function (diffusing capacity of lungs for carbon monoxide [DLcocorr; P=.04) and leukoencephalopathy (P=.02) also were linked to higher radiation dose.
Reduce cognitive fluency occurred in survivors with leukoencephalopathy (P=.001).
The researchers reported a link between working memory impairment and E/E’, and impaired sustained attention and naming speed were linked to DLcocorr.
The researchers also observed a relationship between neurocognitive performance and academic and vocational functioning.
“Survivors of Hodgkin’s lymphoma treated with increasing doses of mantle field radiation are at risk for neurocognitive impairment that requires therapeutic interventions and, given the delayed onset, preventive interventions should be considered,” Krull and colleagues wrote. “Primary prevention has begun with the transition from mantle field radiation to modern protocols that incorporate combined-modality therapy with reduced dose, limited-volume radiation, and polychemotherapy (eg, anthracyclines and bleomycin).
“Although this approach may reduce long-term morbidity, significant risk is likely to remain, given the known associations between anthracyclines and cardiac toxicity and bleomycin and pulmonary toxicity,” the researchers added. “Longitudinal follow-up of such cohorts will be important to fully evaluate long-term neurocognitive and [central nervous system] pathology outcomes.”
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