Iron overload as a risk factor for poor graft function following allogeneic hematopoietic stem cell transplantation

Abstract

Hematological malignancies are increasingly treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, iron overload is a frequent adverse effect of allo-HSCT and is associated with poor prognosis. In the present study, we investigated hematopoiesis in iron-overloaded mice and elucidated the effects of iron overload on the bone marrow (BM) microenvironment. Ironoverloaded BALB/C mice were generated by injecting 20 mg/mL saccharated iron oxide intraperitoneally. Hematoxylin-eosin staining was performed to evaluate the effects of an iron overload in mice. BM cells obtained from C57BL/6 mice were transplanted into irradiated BALB/C mice (whole-body irradiation of 4 Gy, twice with a 4-hours interval) by tail vein injection. Two weeks after allo-HSCT, the hematopoietic reconstitution capacity was evaluated in recipients by colony-forming assays. Histopathological examinations showed brown-stained granular deposits, irregularly arranged lymphocytes in the liver tissues, and blue-stained blocks in the BM collected from mice received injections of high-dose saccharated iron oxide (20 mg/mL). Ironoverloaded mice showed more platelets, higher-hemoglobin (HGB) concentration, fewer granulocyte-macrophage colony-forming units (CFU-GM), erythrocyte colonyforming units (CFU-E), and mixed granulocyte/erythrocyte/monocyte/megakaryocyte colony-forming units (CFU-mix) than healthy mice. Iron-overloaded recipients presented with reduced erythrocytes and HGB concentration in peripheral blood, along with decreased marrow stroma cells, CFU-GM, CFU-E, and CFU-mix relative to healthy recipients. Taken together, our findings demonstrate that iron overload might alter the number of red blood cells after transplantation in mice by destroying the

Granulocyte colony-stimulating factor and decitabine-containing conditioning improves survival in myelodysplastic syndrome patients with iron overload undergoing allogeneic hematopoietic stem cell transplantation

“…Besides, oxidative stress plays an important role in the mechanism of iron overload, affecting not only HSCs but the stromal component of the hematopoietic niche (24)(25)(26)(27). According to our data, patients with iron overload have a slower platelet engraftment than those without, which was also observed in basic researches (28,29). Abnormal bone marrow microenvironment and altered function of bone marrow mesenchymal stromal cells might be implicated in delayed platelet engraftment.…”

The effectiveness of deferasirox to prevent from the occurrence of liver fibrosis in balb/c mice with iron overload

“…Mice administered with IS intraperitoneally for 4 weeks with a low dose (5 mg/mL) did not show any pathological change in the liver's structure, the damage started occurring and there was minimum iron deposit with a medium dose (10 mg/mL). Meanwhile a high dose of iron sucrose (20 mg/mL) showed strong damage to liver structure with the thick brown iron deposit in hepatocyte 44 . Therefore, it is necessary to consider using a variety of doses of iron sucrose to trigger iron overload within the liver.…”

Impact of iron overload on poor graft function after allo-HSCT in a patient with transfusion-dependent low-risk MDS: A case report and literature review

“…[1] IOL may have a deleterious effect on the outcomes of HSCT including HSCT toxicity, relapse risk, and even survival. [2] Moreover, several pre-clinical [3][4][5] and clinical data [6][7][8] suggested that IOL might also affect graft function after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the exact impact of IOL on poor graft function (PGF) and its underlying mechanism have not been fully elucidated.…”