Corticosteriods, Neurocognition and Stress In Adult Survivors of Childhood Leukemia
Authors: Krull Kevin R. , Robison Leslie L. , Ferry Robert J. , Hudson Melissa M. 
Published: October 2019

Abstract
Abstract 738
While recent research has demonstrated comparable neurocognitive outcomes in survivors of childhood leukemia (ALL) treated with different types of corticosteroids during induction therapy, the long-term impact of prolonged corticosteroid therapy has not been investigated. We compared neurocognitive and physiologic outcomes in 37 adult survivors of childhood leukemia who were treated with only chemotherapy (i.e., no cranial radiation therapy) on one of two standard therapy protocols (21 treated with 20 g/m2 HD-IV methotrexate and repeated cycles of prednisone for two years; 16 treated with either 20 or 24 g/m2 HD-IV methotrexate and repeated cycles of dexamethasone for two years). Patients underwent neurocognitive evaluations, physical exams, and laboratory tests after overnight fasting. Morning cortisol was assessed at baseline and 12 h after 1 mg dexamethasone (standard dexamethasone suppression test). Groups were similar for male:female ratio (p=0.73), current age (p=0.90), and cumulative HD-IV methotrexate exposure (p=0.68). No differences were detected in final adult height (p=0.85), body mass index (p=0.43), HDL (p=0.86) or LDL (p=0.99) cholesterol, heart rate (p=0.49), triglycerides (p=0.59), serum glucose (p=0.84), insulin (p=0.63), HgA1C (p=0.62), free T4 (p=0.78), IGF-I (p=0.77), or basal morning cortisol (p=0.72). Survivors treated with dexamethasone displayed significantly higher systolic blood pressure compared to the prednisone exposure group (mean=128.5 ± SD 11.71 vs. 117.7±13.78; p=0.02), and a trend for higher diastolic BP (mean=75.1±9.33 vs. 68.7±10.55; p=0.08). Survivors originally treated with dexamethasone displayed significantly less suppression of cortisol following the dexamethasone suppression test (mean 3.82±6.41 μg/dL) compared to those originally treated with prednisone (0.94 ± 0.75 μg/dL; p=0.05). The dexamethasone group demonstrated significantly lower performance on multiple measures neurocognitive function (Tables 1), including mathematical problem solving (p=0.002), semantic verbal memory (p=0.006) and cognitive flexibility (p=0.02). They also reported more difficulty with emotional regulation (p=0.04). These results suggest that adult survivors of childhood leukemia treated with dexamethasone are at increased risk for neurocognitive impairment and poor emotional regulation. These problems may occur in the presence of symptoms of physical stress. Surprisingly, these survivors appear to display persistent late signs of increased reactivity within the hypothalamic-pituitary-adrenal axis.
Table 1. Group comparison on neurocognitive outcomes. Neurocognitive Outcomes Prednisone (n=21) Dexamethasone (n=16) Group Comparison p-value Mean SD Mean SD Intellect 1 Vocabulary 100.2 15.56 86.4 18.72 0.02 Matrices 103.2 15.08 103.1 7.50 0.99 Academics 2 Reading 100.2 6.62 86.8 16.48 0.002 Mathematics 100.8 9.72 86.6 15.53 0.002 Processing Speed Reaction time3 45.0 9.35 50.5 10.97 0.12 Visual-Motor Speed4 11.6 3.29 8.8 3.44 0.02 Attention Focused5 102.1 17.98 96.1 19.01 0.35 Span6 101.1 11.11 97.4 16.68 0.43 Sustained3 56.2 20.41 54.3 12.73 0.76 Memory 7 Immediate Semantic 11.0 3.24 8.6 2.34 0.02 Delay Semantic 11.5 2.60 8.9 2.43 0.006 Spatial Locations 9.9 2.99 8.6 3.29 0.25 Facial Memory 10.7 3.16 9.6 2.79 0.31 Executive Function Working Memory6 101.3 9.97 94.5 14.66 0.11 Cognitive Flexibility5 103.1 14.63 84.0 31.89 0.02 Cognitive Fluency8 9.7 2.83 8.5 2.95 0.25 1 Wechsler Abbreviated Test of Intelligence; 2 Woodcock-Johnson-III; 3 Connors Continuous Performance Test-II; 4 Weschler Coding/Digit Symbol subtest; 5 Trail Making Test; 6 Wechsler Digit Span subtest (Forward=Span, Backward=Working Memory); 7 Test of Memory and Learning-II; 8 Controlled Oral Word Test.

Disclosures:
No relevant conflicts of interest to declare.