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Dexamethasone exposure and memory function in adult survivors of childhood acute lymphoblastic leukemia: A report from the SJLIFE cohort.

ABSTRACT: Dexamethasone is used in acute lymphoblastic leukemia (ALL) treatment, though long-term impact on central nervous system (CNS) function is unclear. As glucocorticoids influence hippocampal function, we investigated memory networks in survivors of childhood ALL treated with dexamethasone or prednisone.Neurocognitive assessment and functional magnetic resonance imaging (fMRI) were conducted in 38 adult survivors randomly recruited from cohorts treated on one of two standard treatment protocols, which differed primarily in the glucocorticoid administered during continuation therapy (dexamethasone [n?=?18] vs. prednisone [n?=?20]). Groups did not differ in age at diagnosis, age at evaluation, or cumulative intravenous or intrathecal methotrexate exposure.Survivors treated with dexamethasone demonstrated lower performance on multiple memory-dependent measures, including story memory (P?=?0.01) and word recognition (P?=?0.04), compared to survivors treated with only prednisone. Dexamethasone treatment was associated with decreased fMRI activity in the left retrosplenial brain region (effect size?=?1.3), though the small sample size limited statistical significance (P?=?0.08). Story memory was associated with altered activation in left inferior frontal-temporal brain regions (P?=?0.007).Results from this pilot study suggest that adult survivors of ALL treated with dexamethasone are at increased risk for memory deficits and altered neural activity in specific brain regions and networks associated with memory function.

SUBMITTER: Edelmann MN

PROVIDER: S-EPMC3928631 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Dexamethasone exposure and memory function in adult survivors of childhood acute lymphoblastic leukemia: A report from the SJLIFE cohort.

Edelmann Michelle N MN Ogg Robert J RJ Scoggins Matthew A MA Brinkman Tara M TM Sabin Noah D ND Pui Ching-Hon CH Srivastava Deo Kumar DK Robison Leslie L LL Hudson Melissa M MM Krull Kevin R KR

Pediatric blood & cancer 20130618 11

<h4>Background</h4>Dexamethasone is used in acute lymphoblastic leukemia (ALL) treatment, though long-term impact on central nervous system (CNS) function is unclear. As glucocorticoids influence hippocampal function, we investigated memory networks in survivors of childhood ALL treated with dexamethasone or prednisone.<h4>Procedure</h4>Neurocognitive assessment and functional magnetic resonance imaging (fMRI) were conducted in 38 adult survivors randomly recruited from cohorts treated on one of ...[more]

PMID: 23775832

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Project description:Study questionDoes lower dose (<26 Gy) cranial radiation therapy (CRT) used for central nervous system prophylaxis in acute lymphoblastic leukemia (ALL) adversely affect sperm concentration or morphology?Summary answerCRT doses <26 Gy had no demonstrable adverse effect on sperm concentration or morphology.What is known alreadyTreatment with alkylating agents produces oligospermia and azoospermia in some patients. No prior study has been large enough to evaluate the independent effects of alkylating agents and lower dose (<26 Gy) CRT on sperm concentration or morphology.Study design, size, durationThis cross-sectional study included male adult survivors of pediatric ALL who had received alkylating agent chemotherapy with or without CRT and who enrolled in the St. Jude Lifetime Cohort Study (SJLIFE) from September 2007 to October 2013.Participants/materials, setting, methodsThe inclusion criteria were males, ≥18 years of age, ≥10 years after diagnosis, treated at St. Jude Children's Research Hospital for ALL, and received alkylating agent chemotherapy. Semen analyses were performed on 173 of the 241 (78.1%) adult survivors of pediatric ALL who had received alkylating agent chemotherapy with or without CRT. Cumulative alkylating agent treatment was quantified using the cyclophosphamide equivalent dose (CED). Log-binomial multivariable models were used to calculate relative risks (RRs) and 95% CI.Main results and the role of chanceCompared to those without CRT, risk of oligospermia or azoospermia was not increased for CRT <20 Gy (P = 0.95) or 20-26 Gy (P = 0.58). Participants 5-9 years of age at diagnosis compared to those 0-4 years of age (RR = 1.30, 95% CI, 1.05-.61) or those treated with 8-12 g/m2 CED (RR = 2.06, 95% CI, 1.08-3.94) or ≥12 g/m2 CED (RR = 2.12, 95% CI, 1.09-4.12) compared to those treated with >0 to <4 g/m2 CED had an increased risk for oligospermia or azoospermia.Limitations, reasons for cautionOur study relied on the results of one semen analysis. ALL survivors who did not participate in SJLIFE or who declined to submit a semen analysis may also have biased our results regarding the proportion with azoospermia or oligospermia, since those who provided a semen specimen were less likely to have previously fathered children compared to those who did not. The lower rate of previous parenthood among participants may have resulted in a higher observed frequency of azoospermia and oligospermia.Wider implications of the findingsTreatment with <26 Gy CRT did not increase the risk of oligospermia or azoospermia, although a CED exceeding 8 g/m2 and an age at diagnosis of 5-9 years did increase risk of oligospermia and azoospermia. These findings can be used to counsel adult survivors of pediatric ALL.Study funding/competing interest(s)This work was supported by the National Institutes of Health (grant numbers CA 21765, CA 195547, CA00874) and the American Lebanese Syrian Associated Charities (ALSAC). The authors have no competing interests to declare.

Dataset Information

Dexamethasone exposure and memory function in adult survivors of childhood acute lymphoblastic leukemia: A report from the SJLIFE cohort.

Publications

Dexamethasone exposure and memory function in adult survivors of childhood acute lymphoblastic leukemia: A report from the SJLIFE cohort.

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