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

Wu, Xueqiong; Lin, Kangni; Chen, Minmin; Jiang, Peifang; Zhang, Yuxin; Yongquan, Chen; Chen, Qiuru; Xiao, Min; Zhu, Haojie; Issa, Hajji Ally; Chen, Shaozhen; Luo, Xiaofeng; Ren, Jinhua; Li, Qian; Zeng, Yanwei; Xu, Jingjing; Lin, Yifeng; Zheng, Rong; Zheng, Zhihong; Chen, Zhizhe; Hu, Jianda; Yang, Ting

doi:10.1002/kjm2.12238

Cited by 3 publications

(2 citation statements)

References 26 publications

(41 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Sarosa

Wajiih

Indrayani

2023

Bangladesh J Med Sci

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Background: Oxidation of hepatocyte mitochondria due to iron overload led to hepatocyte injury, elevated Transforming growth factor- β (TGF- β), and fibrosis. Fibrosis starts with stellate cell fibrogenesis activated by chronic hepatocyte injury. Liver fibrosis is the main cause of morbidity and mortality in iron overload. Deferasirox is an iron chelation drug serving to bind iron overload and have an antifibrotic effect. Aim: To examine the effect of deferasirox on liver fibrosis prevention due to iron overload. Methods: This experimental research used a post-test only control group design on male Balb/c mice that were randomly divided into 3 groups, each n=5. Group 1 (NaCl+S) was administered with 0.3 cc Na Cl 0.9% through intra peritoneal (I.P) injection and drug solvent (Aquabidest, CMC and Nipagin) per oral (P.O) intermittently. Group 2 (Fe+S) was administered with 0.3 cc 1.5 mg Fe+sucrose (Venofer®) through I.P injection and drug solvent (Aquabidest, CMC and Nipagin) P.O intermittently. Group 3 (Fe+Dfx) 0.3 cc 1.5 mg Fe+sucrose (Venofer®) I.P injection, and deferasirox 20 mg/kgBW/day P.O intermittently. All of the treatments were given for 60 days. The fibrosis area fraction of the liverwas assessed using software ImageJ. Results: The average fibrosis area fraction of group 1 was 0.00 ± 0.00%, group 2 was 9.17 ± 8.54% and group 3 was 1.38 ± 0.20%. The fibrosis area fractions between groups 2 and 3 were significantly different with p value 0.000 (p<0.05). The body weight of group 2 was higher than that of groups 3 and 1. Conclusions: Iron overload causes liver fibrosis in male Balb/c mice. Deferasirox administration may lower the area of liver fibrosis in male Balb/c mice due to iron overload. Bangladesh Journal of Medical Science Vol. 22 No. 01 January’23 Page : 84-90

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Section: Discussionmentioning

confidence: 99%

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

Sarosa

Wajiih

Indrayani

2023

Bangladesh J Med Sci

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“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Rationale: Poor graft function (PGF) occurs in 5% to 27% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high life-threatening complications. The etiology of PGF is complex and multifactorial, and iron overload (IOL) is considered as a predictive factor. Patient concern: A 45-years-old woman who was diagnosed as low-risk myelodysplastic syndrome in 2012 has been transfusion dependent and developed severe IOL. Diagnoses: Due to transfusion dependency and also ineffective erythropoiesis, this patient was diagnosed as IOL and developed PGF after allo-HSCT. Interventions: Deferasirox (20mg/kg/d) was administered regularly after allo-HSCT for 2 years. Outcomes: Hematopoiesis was gradually recovered during iron chelation therapy treatment after allo-HSCT and PGF was reverted. Lessons: IOL, as a prognostic factor for PGF, is a common problem in Transfusion dependent myelodysplastic syndrome patients undergoing HSCT. IOL issues should be considered at the time of diagnosis and throughout the treatment course for patients who are potential candidates for HSCT.

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

Zhao

Pan

Xuan

et al. 2023

Preprint

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Background: Iron overload is considered as an unfavorable prognosis in myelodysplastic syndrome (MDS) even in those undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although iron chelation therapy has improved the prognosis of these patients to some extent, the effect has not yet been satisfactory. This study aimed to investigate whether granulocyte colony-stimulating factor and decitabine (G-DAC)-containing conditioning improve the prognosis of iron-overloaded MDS patients undergoing allo-HSCT. Methods: One hundred and ninety-seven patients were enrolled in this retrospective study. Based on the level of serum ferritin (SF) and conditioning regimen, all patients enrolled were divided into 4 groups: SF﹤1000µg/L with G-DAC conditioning (cohort 1), SF﹤1000µg/L with non-G-DAC conditioning (cohort 2), SF ≥ 1000µg/L with G-DAC conditioning (cohort 3) and SF ≥ 1000µg/L with non-G-DAC conditioning (cohort 4). The clinical features and prognosis between cohorts were analyzed. Results: The 2-year overall survival (OS) was 77.0%, 72.1%, 73.8% and 38.7% (P = 0.001), and disease-free survival (DFS) was 75.7%, 62.8%, 71.7% and 35.5% (P= 0.001), and the cumulative incidence of non-relapse mortality (NRM) was 17.3%, 25.0%, 15.2% and 53.1% (P = 0.001), and the incidence of relapse was8%, 13.6%, 13.1% and 12.5% (P = 0.592), respectively, in the four groups. To be specific, cohort4 had worse OS and DFS and higher NRM than the other three groups (all P﹤0.05). Multivariate analysis revealed that SF ≥ 1000µg/L was a risk factor for OS, DFS and NRM (P = 0.022, P = 0.025, P = 0.036), while G-DAC-containin g conditioning was a protective factor (P = 0.009, P = 0.003, P = 0.004). Intriguingly, when cohort 1 to cohort4 were included in the multivariate analysis, only cohort4 was a risk factor for OS, DFS and NRM (all P﹤0.05), but cohort3, namely iron-overloaded patients who received G-DAC-containing conditioning had no difference in prognosis compared with patients with SF﹤1000µg/L. Conclusions: The poor prognosis of patients with iron overload could be overcome byG-DAC-containing conditioning partly.

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

Cited by 3 publications

References 26 publications

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

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

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

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

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