Nutritional interventions in children with acute lymphoblastic leukemia undergoing antineoplastic treatment: a systematic review

Abstract

Background: A compromised nutritional status jeopardizes a positive prognosis in acute lymphoblastic leukemia (ALL) patients. In low- and middle-income countries, ~ 50% of children with ALL are malnourished at diagnosis time, and undergoing antineoplastic treatment increases the risk of depleting their nutrient stores. Nutrition interventions are implemented in patients with cancer related malnutrition. We aimed to evaluate the effect of nutrition interventions in children diagnosed with ALL under treatment.

Methods: Using a predefined protocol, we searched for published or unpublished randomized controlled trials in: Cochrane CENTRAL, MEDLINE, EMBASE, LILACS, and SciELO, and conducted complementary searches. Studies where at least 50% of participants had an ALL diagnosis in children ≤ 18 years, active antineoplastic treatment, and a nutrition intervention were included. Study selection and data extraction were conducted independently by three reviewers, and assessment of the risk of bias by two reviewers. Results were synthesized in both tabular format and narratively.

Results: Twenty-five studies (out of 4097 records) satisfied the inclusion requirements. There was a high risk of bias in eighteen studies. Interventions analyzed were classified by compound/food (n = 14), micronutrient (n = 8), and nutritional support (n = 3). Within each group the interventions and components (dose and time) tested were heterogeneous. In relation to our primary outcomes, none of the studies reported fat-free mass as an outcome. Inflammatory and metabolic markers related to nutritional status and anthropometric measurements were reported in many studies but varied greatly across the studies. For our secondary outcomes, fat mass or total body water were not reported as an outcome in any of the studies. However, some different adverse events were reported in some studies.

Conclusions: This review highlights the need to conduct high-quality randomized controlled trials for nutrition interventions in children with ALL, based on their limited number and heterogeneous outcomes.

Registration of the review protocol: Guzmán-León AE, Lopez-Teros V, Avila-Prado J, Bracamontes-Picos L, Haby MM, Stein K. Protocol for a Systematic Review: Nutritional interventions in children with acute lymphoblastic leukemia undergoing an tineoplastic treatment. International prospective register of systematic reviews. 2021; PROSPERO CRD:42,021,266,761 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=266761 ).

Keywords: Malnutrition; Nutrition intervention; Pediatric acute lymphoblastic leukemia; Systematic review.

Fig. 1

PRISMA flow diagram for the systematic review. ALL, acute lymphoblastic leukemia

Fig. 2

Risk of bias graph. Judgements about each risk of bias item presented as percentages across all included studies. In the x axis are the percentages, and the y axis shows the different types of bias. In green are classified the studies that meet the criteria for a low risk of bias, in yellow those with an unclear risk of bias, and in red the ones with high risk of bias