Iron overload in the HCT patient: a review

Abstract

Iron overload (IO) is common in hematologic malignancies and hemoglobinopathies, largely due to red cell transfusion burden. End-organ damage from IO occurs via reactive oxygen species-mediated pathways. The impact of pretransplant IO on hematopoietic cell transplant (HCT) morbidity and mortality remains contentious; studies have shown mixed results, possibly due to variability in study population and design, as well as markers of IO. Ferritin has served as a traditional circulating marker of total body IO, but liver iron content by MRI appears to be a better marker of end-organ involvement. Novel surrogate markers including hepcidin, marrow Prussian blue staining, and labile plasma iron levels may prove to be more specific for HCT complications. Posttransplant phlebotomy, chelation, or both in combination remains the mainstays of treatment, though may ultimately be supplanted by pretransplant or peri-transplant use of bone marrow maturation agents or targeted chelation at time of highest IO risk. This review discusses the pathophysiology of IO in hematologic disease, the evidence supporting and refuting its negative impact on HCT outcomes, as well as current and future therapies.