Non‐transferrin‐bound iron induced by myeloablative chemotherapy

Abstract

Summary. Previous studies have suggested that nontransferrin-bound plasma iron (NTBI) is present in patients undergoing cytotoxic chemotherapy, and that this may exacerbate untoward organ damage and increase the risk of bacterial infections following chemotherapy. However, the source of NTBI during myelosuppressive chemotherapy is controversial. In this study we have examined the kinetics of the appearance and disappearance of NTBI with chemotherapy. NTBI was present in only two out of 24 patients prior to chemotherapy but, following chemotherapy, was present in 19 patients, with peak NTBI levels at 5 d after onset of chemotherapy (mean 3 . 06 mM). Thereafter levels fell, but were still detectable in seven patients 14 d after the end of chemotherapy. The appearance of NTBI was associated with a sudden rise in transferrin saturation, but NTBI was detected on four occasions in the absence of full transferrin saturation. We have also established that daunorubicin cannot itself liberate NTBI from serum. There was no relationship between induced NTBI levels and serum iron or ferritin levels, previous or current blood transfusions, disease stage, or the type of chemotherapy given. The appearance of NTBI following chemotherapy was inverserely related to the fall in reticulocytes and serum transferrin receptor (TfR) levels, suggesting that NTBI formation is a consequence of suspension of erythropoietic activity.

Non Transferrin Bound Iron: Nature, Manifestations and Analytical Approaches for Estimation

“…Mingwei et al suggested that glycated proteins whose concentration is high in diabetics, do not only bind to iron and copper with higher affinity but also have the tendency to extract the iron from the traditional iron carriers [23]. In case of cancer patients undergoing for chemotherapy the reasons for the existence of NTBI are due to temporary shutdown of bone marrow and associated reduced demand of iron [24][25][26][27]. The other clinical conditions in which the presence of NTBI is indicated are acute coronary syndrome, liver disease, end stage kidney disease patients who are undergoing dialysis, in chronic alcoholics, myelodysplastic syndrome etc.…”

“…Since mature RBCs are devoid of TFR this uptake is necessary of non Tf iron [115]. NTBI is also found in patients of hematologic malignancies undergoing high-dose chemotherapy, particularly those treated with myeloablative therapy and stem cell transplantation [24,27,55].…”

Genomic screening and complications of hematopoietic stem cell transplantation: has the time come?

“…[93][94][95] Prevalent iron-loading genetic mutations such as HFE C282Y may also augment organ toxicity (eg HVOD) by promoting infection, increasing reactive iron levels, and/or impairing the re-uptake of iron that is released during myeloablation. 32,[96][97][98][99][100][101][102][103] These mutations may also predispose HSCT survivors to secondary myelodysplasia and other malignancies. [104][105][106][107][108][109] The effects of iron in the HSCT setting deserve further investigation, since they contribute to long-term morbidity and are potentially modifiable by antioxidant therapy, phlebotomy, and chelation.…”

Improved quantification for non-transferrin-bound iron measurement using high-performance liquid chromatography by reducing iron contamination

“…However, various methods have been reported (19). As sensitivities have been improving, it was noted that NTBI is likely to exist even under physiological conditions when Tf is not fully saturated (5,20). This observation suggests that NTBI was not merely excess iron above the iron binding capacity of Tf.…”