Iron overload, hematopoietic cell transplantation, and graft-versus-host disease

Abstract

Many patients who undergo hematopoietic cell transplantation (HCT) present with anemia and have received red blood cell transfusions before HCT. As a result, iron overload is frequent and appears to be particularly prominent in patients with myelodysplastic syndromes (MDS). There is evidence that peritransplant events contribute to further iron accumulation, although the mechanism that disrupts normal iron homeostasis remains to be determined. Recent studies suggest that iron overload, as determined by ferritin levels, a surrogate marker for iron, is a risk factor for increased non-relapse mortality after HCT. Iron overload is associated with an increased rate of infections, in particular with fungal organisms. Furthermore. anecdotal data suggest that increased hepatic iron may mimic the clinical picture of (chronic) graft-versus-host-disease (GVHD). Whether excess iron contributes to GVHD and whether iron depletion, be it by phlebotomy or chelation, reduces the posttransplantation complication rate and improves transplant outcome has yet to be determined.

Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging

“…In the clinical setting, one of the risk factors for IA in immunocompromised patients is a high iron load [38], which is frequently occurs due to blood transfusions or iron supplementation during the course of their underlying disease. As 68 Ga-siderophores mimic iron-transporting mechanisms in microorganisms, we wanted to see whether an iron preload would have an effect on the uptake of 68 Ga-labelled siderophores in the IA rat model.…”

Hepatic veno-occlusive disease may develop in secondary iron overloaded mice after allogeneic hematopoietic stem cell transplantation with total body irradiation

“…Hepatic iron overload induced liver damage by ROS [ 1 2 9 19 23 ], and radiation in HSCT contributed to hepatic injury caused by ROS and free radicals [ 16 21 23 ]. In HSCT, iron accumulation in the liver plays a major role in the development of hepatic VOD, while radiation has also been associated with VOD [ 6 7 8 ]. Our study has some limitations in terms of the evaluation for long-term biological effects between iron overload and hepatic injury in SIO mice after allogeneic HSCT.…”

“…Our study has some limitations in terms of the evaluation for long-term biological effects between iron overload and hepatic injury in SIO mice after allogeneic HSCT. As previously mentioned, we need to study the relationship between iron overload and graft-versus-host disease, and whether iron overload induces inflammation and aggravates GVHD in allogeneic HSCT [ 6 7 ].…”

“…In patients with transfusion dependency, the mortality and morbidity after HSCT were related to the iron burden [ 5 ]. HSCT in patients with SIO resulted in high infection rates, acute graft-versus-host disease (GVHD), and hepatic veno-occlusive disease (VOD) in the early post-trans plant period, and high infection, cardiac fibrosis, and abnormal liver function in the late post-transplant period [ 6 7 8 9 ]. High level of serum ferritin as a surrogate marker of SIO was related to risk of acute GVHD and VOD [ 7 10 ].…”

Iron Overload in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

“…In fact, iron overload is a well-established adverse prognostic factor in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) for thalassemia [1,2], but more recently it appears to play a similar role in patients with other hematological disorders [3][4][5][6][7]. In this respect, there are studies indicating that iron overload may be considered as a risk factor contributing to post-transplant liver toxicity, veno-occlusive disease (VOD), infection susceptibility and graft-versus-host disease (GVHD) and may negatively impact survival as well [8][9][10].…”