Assessmet of Labile Plasma Iron and Hepcidin in Patients Who Undergo Hematopoietic Stem Cell Transplantation

Abstract

Nontransferrin-bound iron (NTBI) has been reported shortly after myeloablative conditioning in patients undergoing hematopoietic stem cell transplantation (HSCT), and it is assumed that the appearance of unbound iron in this nontransfusion setting possibly reflects a major disturbance in body iron distribution, which is related mainly to its underutilization due to erythropoiesis suppression. There is a concern that labile plasma iron (LPI), the most toxic fraction of NTBI that includes the redox-active forms of iron, can be involved in the occurrence of toxicity and other complications commonly observed in the early post-HSCT period. Recently, we demonstrated that LPI levels, albeit normal at baseline measurements, increased substantially 48 hours after the start of conditioning in HSCT patients and remained increased until engraftment, when it returned to normal levels (Acta Haematol 2014;131:222-226). Here we provide a more detailed analysis of iron status in HSCT patients by adding determinations of hepcidin and standard iron parameters along with LPI in 25 adult patients undergoing first autologous HSCT following myeloablative conditioning. All iron parameters were determined before the start of conditioning (baseline), on day 0 (before stem cells infusion) and upon documented engraftment (Table). The fast and substantial increase in LPI levels on day 0, indeed reflected a disruption of iron homeostasis by conditioning, that was accompanied by a response in hepcidin and TfS levels. However, reutilization of iron by a restored erythropoiesis upon engraftment lead to a substantial drop in LPI, but not in hepcidin levels, possibly due to the fact that production of hepcidin by the liver is not only modulated by iron loading and erythropoietic activity, but also inflammation. Ferritin baseline levels were already increased and did not change throughout the study. Considering all determinations (baseline, day 0 and engraftment), hepcidin levels correlated positively with ferritin (r=0,43; p=0,01; Figure Panel A) and TfS (r=0,37; p=0,02; Figure Panel B); and LPI correlated positively with TfS (r=4,3; p=0,002; Figure Panel C), although increased LPI levels were observed with normal TfS levels in some patients. A tendency of correlation between hepcidin and LPI was found considering only baseline and day 0 levels (r=0,30; p=0,05; Figure Panel D). These results indicate that LPI reflected better the changes in iron status caused by cytotoxic chemotherapy in HSCT patients, and could serve as a target in the eventuality of chelation therapy in the early period of HSCT. The other iron parameters were probably influenced by inflammation, even upon engraftment, and would not behave as appropriate surrogate markers for increased LPI levels.*LPI levels <0.5μM are considered normal.† p<0,05 in relation to baseline levels. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.