Smaller white-matter volumes are associated with larger deficits in attention and learning among long-term survivors of acute lymphoblastic leukemia

Abstract

Background: The primary objective of this study was to test the hypothesis that survivors of childhood acute lymphoblastic leukemia (ALL) have deficits in neurocognitive performance, and smaller white-matter volumes are associated with these deficits.

Methods: The patients studied included 112 ALL survivors (84 patients who had received chemotherapy only, 28 patients who had received chemotherapy and irradiation; 63 males, 49 females; mean age +/- standard deviation, 4.1 yrs +/- 2.6 yrs at diagnosis; mean +/- standard deviation yrs since diagnosis, 6.0 +/- 3.5 yrs), and 33 healthy siblings who participated as a control group. Neurocognitive tests of attention, intelligence, and academic achievement were performed; and magnetic resonance images were obtained and subsequently were segmented to yield tissue volume measurements. Comparisons of neurocognitive measures and tissue volumes between groups were performed, and the correlations between volumes and neurocognitive performance measures were assessed.

Results: Most performance measures demonstrated statistically significant differences from the normative test scores, but only attention measures exceeded 1.0 standard deviation from normal. Patients who had received chemotherapy alone had significantly larger volumes of white matter than patients who had received treatment that also included cranial irradiation, but their volumes remained significantly smaller than the volumes in the control group. Smaller white-matter volumes were associated significantly with larger deficits in attention, intelligence, and academic achievement.

Conclusions: Survivors of childhood ALL had significant deficits in attention and smaller white-matter volumes that were associated directly with impaired neurocognitive performance. Cranial irradiation exacerbated these deficits.

FIGURE 1

The normal-appearing, sagittal, T1-weighted image on the far left shows a box that denotes the coverage of the 5 transverse sections that were used in the current study. The remaining images, from left to right, are representative transverse T1-weighted, T2-weighted, and proton density-weighted images that were used to create the segmented map on the far right.

FIGURE 2

A representative fluid-attenuated, inversion-recovery image (left) and the resulting segmented map (right) demonstrate the white matter hyperintensities that were observed during therapy in a patient with acute lymphoblastic leukemia who received treatment with chemotherapy alone.