Assessment of Labile Plasma Iron in Patients Who Undergo Hematopoietic Stem Cell Transplantation

Abstract

Body iron disorders have been reported after myeloablative conditioning in patients undergoing hematopoietic stem cell transplantation (HSCT). There is a concern that labile plasma iron (LPI), the redox-active form of iron, can be involved in the occurrence of toxicity and other complications commonly observed in the early post-HSCT period. In order to better understand the LPI kinetics and its determinants and implications, we undertook sequential LPI determinations before and after conditioning until engraftment in 25 auto-HSCT patients. Increased LPI was present in only 5 patients before starting conditioning. Shortly after conditioning, LPI levels were increased in 23 patients, with peak at day 0, returning to normal range upon engraftment in 21 patients. Overall, LPI levels correlated weakly with serum ferritin and more strongly with transferrin saturation; however, both parameters were apparently not applicable as surrogate markers for increased LPI. Although this was a small cohort, logistic regression suggested that baseline LPI levels could predict occurrence of grade III or IV toxicity. In conclusion, LPI kinetics is influenced by aplasia following conditioning and engraftment. Measuring LPI before starting conditioning can offer an opportunity to predict toxicity and, perhaps, the need for chelation therapy.

Design and Validation of an Augmented Hematopoietic Cell Transplantation-Comorbidity Index Comprising Pretransplant Ferritin, Albumin, and Platelet Count for Prediction of Outcomes after Allogeneic Transplantation

“…This interpretation is consistent with results of previous studies showing that adjustment for hypoalbuminemia did not attenuate the risk of NRM associated with high serum ferritin concentrations [19]. Other investigators have suggested that high ferritin levels may correlate with the effects of acute iron toxicity, and that pre-HCT transfusion burden [30] or specific biomarkers measuring circulating free iron may serve as more reliable prognostic variables [20,36]. Additional studies are needed to better characterize the physiologic basis of ferritin’s prognostic impact as it could have significant implications for the incorporation of iron chelation as part of peri-HCT care [37,38].…”

Serum ferritin is not a reliable predictor to determine iron overload in thalassemia major patients post‐hematopoietic stem cell transplantation

“…Based on intensive red cell transfusion and massive mobilization of iron deposits from marrow cell destruction following HSCT, non-transferrin-bound iron (NTBI) and labile plasma iron (LPI) are increased in the peritransplant period. 5,34 Recently, Wemke and colleagues could show that enhanced LPI prior to HSCT had a significantly increased incidence of non-relapsed mortality in patients with AML and MDS. 35 New findings in the understanding of iron metabolism in the peri-and post-transplant period may be useful to treat patients with IO in the HSCT setting more accurately, but specific and prospective studies are needed.…”

Management of iron overload in hemoglobinopathies: what is the appropriate target iron level?

“…For example, LPI goes up within 3–4 days of starting preparative chemotherapy for bone marrow transplant owing to loss of marrow activity, even in patients who are not transfused. The levels of NTBI/LPI return to normal after transplant as engraftment occurs and erythropoiesis resumes . Transferrin saturation can be very elevated for years in nontransfused, low‐risk myelodysplastic syndrome (MDS) patients owing to marked ineffective erythropoiesis.…”