Growth hormone deficiency and neurocognitive function in adult survivors of childhood acute lymphoblastic leukemia Journal Article


Authors: Krull, K. R.; Li, C.; Phillips, N. S.; Cheung, Y. T.; Brinkman, T. M.; Wilson, C. L.; Armstrong, G. T.; Khan, R. B.; Merchant, T. E.; Sabin, N. D.; Srivastava, D.; Pui, C. H.; Robison, L. L.; Hudson, M. M.; Sklar, C. A.; Chemaitilly, W.
Article Title: Growth hormone deficiency and neurocognitive function in adult survivors of childhood acute lymphoblastic leukemia
Abstract: Background: The impact of growth hormone deficiency (GHD) on neurocognitive function is poorly understood in survivors of childhood acute lymphoblastic leukemia (ALL). This study examined the contribution of GHD to functional outcomes while adjusting for cranial radiation therapy (CRT). Methods: Adult survivors of ALL (N = 571; 49% female; mean age, 37.4 years; age range, 19.4-62.2 years) completed neurocognitive tests and self-reported neurocognitive symptoms, emotional distress, and quality of life. GHD was defined as a previous diagnosis of GHD or a plasma insulin-like growth factor1 level less than −2.0 standard deviations for sex and age at the time of neurocognitive testing. Hypothyroidism, hypogonadism, sex, age at diagnosis, CRT dose, and intrathecal and high-dose intravenous methotrexate were included as covariates in multivariable linear regression models. Results: Of the 571 survivors, 298 (52%) had GHD, and those with GHD received higher doses of CRT (P =.002). Survivors who had GHD, irrespective of prior growth hormone treatment, demonstrated poorer vocabulary (z-score, −0.84 vs −0.61; P =.02), processing speed (z-score, −0.49 vs −0.30; P =.04), cognitive flexibility (z-score, −1.37 vs −0.94; P =.01), and verbal fluency (z-score, −0.74 vs −0.44; P =.001), and they self-reported more neurocognitive problems and poorer quality of life compared with survivors who did not have GHD. Multivariable and mediation models revealed that GHD was associated with small effects on quality of life (general health, P =.01; vitality, P =.01; mental health, P =.01); and CRT dose accounted for the lower neurocognitive outcomes. Conclusions: Adult survivors of childhood ALL who receive CRT are at risk for GHD, although poor neurocognitive outcomes are determined by CRT dose and not by the presence of GHD. © 2019 American Cancer Society
Keywords: adult; cancer survival; controlled study; leukemia; major clinical study; cancer radiotherapy; methotrexate; drug megadose; protein blood level; quality of life; growth hormone; acute lymphoblastic leukemia; growth hormone deficiency; age; cancer survivor; self report; survivors; cognition; somatomedin c; childhood leukemia; mental health; emotional stress; human; male; female; priority journal; article; neurocognitive; verbalization
Journal Title: Cancer
Volume: 125
Issue: 10
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2019-05-15
Start Page: 1748
End Page: 1755
Language: English
DOI: 10.1002/cncr.31975
PUBMED: 30690723
PROVIDER: scopus
PMCID: PMC6486430
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Charles A Sklar
    283 Sklar