Risk factors for steroid-induced adverse psychological reactions and sleep problems in pediatric acute lymphoblastic leukemia: A systematic review

Objective: Steroids play an essential role in treating pediatric acute lymphoblastic leukemia (ALL). The downside is that these drugs can cause severe side effects, such as adverse psychological reactions (APRs) and sleep problems, which can compromise health-related quality of life. This study aimed to systematically review literature to identify risk factors for steroid-induced APRs and sleep problems in children with ALL. Methods: A systematic search was performed in six databases. Titles/abstracts were independently screened by two researchers. Data from each included study was extracted based on predefined items. Risk of bias and level of evidence were assessed, using the Quality in Prognosis Studies tool and the Grading of Recommendations Assessment, Development and Evaluation tool, respectively. Results: Twenty-four articles were included. APR measurement ranged from validated questionnaires to retrospective record retrieval, sleep measurement included questionnaires or actigraphy. Overall, quality of evidence was very low. Current evidence suggests that type/dose of steroid is not related to APRs, but might be to sleep problems. Younger patients seem at risk for behavior problems and older patients for sleep problems. No studies describing parental stress or medical history were identified. Genetic susceptibility associations remain to be replicated. Conclusions: Based on the current evidence, conclusions about risk factors for steroid-induced adverse psychological reactions or sleep problems in children with ALL should be drawn cautiously, since quality of evidence is low and methods of measurement are largely heterogeneous. A standardized registration of steroid-induced APRs/sleep problems and risk factors is warranted for further studies in children with ALL.