The gut microbiome (GM) has emerged as a key factor in the genesis and progression of many diseases. The intestinal bacterial composition is also able to influence treatment-related side effects and even efficacy of oncological therapies. Acute leukemia (AL) is the most common cancer among children and the most frequent cause of death from cancer during childhood. Outcome has improved considerably over the past four decades, with the current long-term survival for acute lymphoblastic leukemia being approximately 90%. However, several acute toxicities and long-term sequela are associated with the multimodal therapy-protocols applied in these patients. Specific GM configurations could contribute in the multistep developmental hypothesis for leukemogenesis. Moreover, GM alterations occur during the AL therapeutic course and are associated with treatment-related complications, especially during hematopoietic stem cell transplantation. The GM perturbation could last even after the removal of microbiome-modifying factors, like antibiotics, chemotherapeutic drugs or allo-immune reactions, contributing to several health-related issues in AL survivors. The aim of this paper is to provide a comprehensive review of the chronological changes of GM in children with AL, from predisposition to cure. The underpinning biological processes and the potential interventions to modulate the GM towards a potentially health-promoting configuration are also highlighted.

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