Hepcidin in Children and Adults with Acute Leukemia or Undergoing Hematopoietic Cell Transplantation: A Systematic Review

SIMPLE SUMMARY: In this systematic review, we summarized the observational studies on hepcidin in patients treated for acute leukemia or undergoing hematopoietic cell transplantation (AL/HCT). Thanks to the rigorous methodology used, we were able to trace the available literature conscientiously and draw the following conclusions: (1) in both children and adults with AL and qualified for HCT, hepcidin levels are high regardless of the phase of the disease or iron resources;, (2) AL therapy, and HCT in particular, may affect hepcidin levels, but the data, especially for children, are fragmented; (3) pre-HCT hepcidin levels may help predict post-HCT outcomes; (4) there is a need to standardize the determination of hepcidin levels in the clinical setting. We find a very large discrepancy in the reported mean and median hepcidin levels, both in healthy subjects and in AL. This significantly hinders the interpretation and comparison of the results. ABSTRACT: Objectives: The association between hepcidin and acute leukemia (AL) or hematopoietic cell transplantation (HCT) in children and adults remains obscure. We aimed to assess this potential relationship through a systematic review of observational studies. Methods: An electronic search of three databases, including PubMed, Scopus, and Web of Science Core Collection, was performed up to 31 March 2022. Two independent reviewers assessed the search results according to predetermined inclusion and exclusion criteria, following PRISMA guidelines. Results: Of the 3607 titles identified, 13 studies published between 2008 and 2021 met the inclusion criteria. Most studies included a moderate number of participants and controls and used enzyme-linked immunosorbent assay (ELISA) to determine serum hepcidin levels. The principal findings: (1) serum hepcidin levels in patients with AL or undergoing HCT are increased compared to controls, regardless of the patient’s age and the phase of disease treatment; (2) AL therapy and HCT significantly influence serum hepcidin levels; (3) serum hepcidin may predict a worse outcome in patients with AL and post-HCT. Conclusions: This systematic review provides an overview of observational studies that deal with the association of hepcidin with AL and HCT. Although disturbances in iron metabolism are common in AL and HCT, and hepcidin seems to play a cardinal role in their modulation, more extensive research is needed.