Unbalance in Iron Metabolism in Childhood Leukemia Converges with Treatment Intensity: Biochemical and Clinical Analysis.

Monika Łęcka,Katarzyna Albrecht,Jan Styczyński,Ewa Żekanowska,Michał Romiszewski,Artur Słomka

doi:10.3390/cancers13123029

Monika Łęcka, Katarzyna Albrecht + Show 4 more

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https://doi.org/10.3390/cancers13123029

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Abstract

Simple SummaryIn children undergoing therapy for acute leukemia or after hematopoietic cell transplantation, the following iron metabolism parameters were analyzed in the context of iron overload: (1) parameters measuring functional and storage iron pools: non-transferrin-bound iron (NTBI) and labile plasma iron (LPI) levels, iron, transferrin, total iron-binding capacity, ferritin, ferritin heavy and light chains; (2) proteins regulating iron absorption and its release from tissue stores: hepcidin, soluble hemojuvelin, soluble ferroportin-1; (3) proteins regulating the erythropoietic activity of bone marrow: erythroferrone, erythropoietin, soluble transferrin receptor. It has been shown that the occurrence of NTBI and LPI in the circulation and the intensification of disturbances in iron metabolism were associated with the intensity of anti-leukemic treatment and were the highest in the transplant group followed by the acute leukemia after treatment and de novo groups. In patients after transplantation, the most significant changes were found in NTBI, LPI, iron, ferritin, hepcidin, and ferroportin-1 levels.Objective: The aim of this study was to evaluate non-transferrin-bound iron (NTBI) and labile plasma iron (LPI) levels and other parameters of iron metabolism in children undergoing therapy for acute leukemia or after hematopoietic cell transplantation (HCT), in the context of iron overload. Patients: A total number of 85 children were prospectively included into four groups: controls, acute leukemia de novo, acute leukemia after intensive treatment, and after HCT. Methods: The following iron metabolism parameters were analyzed: (1) parameters measuring functional and storage iron pools: NTBI, LPI, iron, transferrin, total iron-binding capacity, ferritin, ferritin heavy and light chains; (2) proteins regulating iron absorption and its release from tissue stores: hepcidin, soluble hemojuvelin, soluble ferroportin-1; (3) proteins regulating the erythropoietic activity of bone marrow: erythroferrone, erythropoietin, soluble transferrin receptor. Results: Intensive treatment of leukemia in children was associated with the presence of serum NTBI and LPI, which was the highest in the HCT group followed by the acute leukemia after treatment and de novo groups. In patients after HCT, the most significant changes were found in NTBI, LPI, iron, ferritin, hepcidin, and ferroportin-1 levels. Conclusions: The occurrence of NTBI and LPI in the circulation and the intensification of disturbances in iron metabolism were associated with the intensity of the anti-leukemic treatment.

Highlights

Iron overload is a common secondary complication in patients treated for acute leukemia or undergoing hematopoietic cell transplantation (HCT), resulting from frequent red blood cell transfusions [1,2,3]
To assess iron metabolism as comprehensively as possible, 14 laboratory parameters were analyzed in this study. They included three categories of markers: (1) parameters measuring functional and storage iron pools (NTBI, labile plasma iron (LPI), iron, transferrin, total iron-binding capacity (TIBC), ferritin, ferritin heavy chain (FTH1), and ferritin light chain (FTL)); (2) proteins regulating the absorption of iron and its release from the tissue stores (hepcidin (25-amino acid isoform), soluble hemojuvelin, and soluble ferroportin-1); (3) proteins regulating the erythropoietic activity of bone marrow (erythroferrone (ERFE), erythropoietin (EPO), and soluble transferrin receptor)
non-transferrin-bound iron (NTBI) was detected in all three patient groups, with the highest frequency in children after HCT, and this iron fraction was not found in the control group of healthy children (Table 3)

Summary

Introduction

Iron overload is a common secondary complication in patients treated for acute leukemia or undergoing hematopoietic cell transplantation (HCT), resulting from frequent red blood cell transfusions [1,2,3]. The toxicity of iron results from the Fe2 + forms of iron, which are highly reactive and cause rapid oxidant damage of proteins and DNA, permanently changing the structure of proteins and genetic material [7,8]. This process is mainly caused by the excess of NTBI and its fraction LPI [2]

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