Iron Toxicity and Hemopoietic Cell Transplantation: Time to Change the Paradigm

The issue of iron overload in hemopoietic cell transplantation has been first discussed in the field of transplantation for thalassemia. Thalassemia major is characterized by ineffective erythropoiesis and hemolysis leading to severe anemia. Patients require regular blood transfusion therefore they develop iron overload causing organ damage and hematopoietic cell transplantation (HCT) is a consolidated reliably curative option. In this category of patients an important issue for transplant outcome is the iron burden before transplant and in the long-life post-transplant. Nevertheless today the concept of the impact of iron overload / toxicity on the outcome of HCT has been extended to other diseases characterized by periods of variable duration of transfusion dependence. Recent preclinical data has shown how increased production of reactive oxygen species (ROS) resulting under iron overload condition, could impair the stem cells clonality capacity, proliferation and maturation. Also, microenvironment cells could be affected through this mechanism. For this reason, iron overload is becoming an important issue also in the engraftment period post-transplant. The aim of this review is to update consolidated knowledge about the role of iron overload/iron toxicity in the HCT setting in non-malignant and in malignant diseases introducing the concept of exposition of free toxic iron forms and related cellular damage in the different stage of transplant.