Iron overload in hematopoietic cell transplantation

Majhail, Navneet S.; Lazarus, Hillard M.; Burns, Linda J.

doi:10.1038/bmt.2008.99

Cited by 128 publications

(127 citation statements)

References 67 publications

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“…28 In addition to the adverse impact of iron overload on early infection-related complications, several studies have suggested that high ferritin levels are adversely associated with overall survival and treatment-related mortality. 16,[29][30][31] In agreement with these studies, our results showed that high ferritin levels are associated with a 2.5-fold increased risk of overall mortality and a 5-fold increased risk of higher treatment-related mortality, compared with low ferritin levels. These studies collectively suggest that iron overload is an important and strong prognostic factor in various clinical outcomes of allogeneic HCT.…”

Section: Category Bacterial Isolatessupporting

confidence: 81%

Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation

Kanda

Mizumoto

Ichinohe

et al. 2010

Bone Marrow Transplant

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Although fluoroquinolones or other antibiotics are commonly used to prevent bacterial infections after hematopoietic cell transplantation (HCT), because of the growing presence of multidrug-resistant microorganisms, it is important to identify patients who are more likely to benefit from antibacterial prophylaxis. To evaluate risk factors for early bacterial infection after allogeneic HCT, we retrospectively analyzed clinical data for 112 consecutive adult patients with hematological malignancies who received transplants without any antibacterial prophylaxis. The cumulative incidence of bacterial infection at 30 days after transplantation was 16%. Among various pre-transplant factors, only high serum ferritin (4700 ng/mL, 47 patients) and high C-reactive protein (CRP) (40.3 mg/dL, 28 patients) levels were significantly associated with the development of bacterial infection in a multivariate analysis (hazard ratio (95% confidence interval): ferritin, 4.00 (1.32-12.17); CRP, 3.64 (1.44-9.20)). In addition, septic shock and sepsis with organ failure were exclusively observed in patients who had high ferritin and/or high CRP levels. These results suggest that pretransplant serum ferritin and CRP levels can be useful markers for predicting the risk of early bacterial infection after allogeneic HCT. It may be prudent to limit antibacterial prophylaxis to patients with predefined risk factors to ensure the safety of HCT with the use of fewer antibiotics.

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Section: Category Bacterial Isolatessupporting

confidence: 81%

Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation

Kanda

Mizumoto

Ichinohe

et al. 2010

Bone Marrow Transplant

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“…1 Thus, it is not surprising that elevated serum ferritin (SF) is commonly found after allogeneic hematopoietic stem cell transplantation (HSCT). 2 No physiologic mechanism for iron excretion exists in humans and excess iron could persist for years after HSCT. [2][3][4][5] Additionally, iron homeostasis is frequently complicated by factors known to modulate hepcidin expression such as ineffective erythropoiesis, inflammation, infections and hypoxia.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4][5] Additionally, iron homeostasis is frequently complicated by factors known to modulate hepcidin expression such as ineffective erythropoiesis, inflammation, infections and hypoxia. 6 The negative impact of hyperferritinemia on survival after allogeneic HSCT is well recognized, 1,2,7,8 hepatic dysfunction may be exacerbated [9][10][11] and pre-HSCT iron chelation may be associated with improved survival and reduced non-relapse mortality. 13 Data suggest that post-HSCT SF is comparable to pre-HSCT values, 12 and hyperferritinemia up to day +720 post HSCT could significantly be associated with decreased survival.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

Jaekel

Lieder

Albrecht

et al. 2015

Bone Marrow Transplant

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Elevated serum ferritin contributes to treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The multicenter DE02 trial assessed the safety, efficacy and impact of deferasirox on iron homeostasis after allogeneic HSCT. Deferasirox was administered at a starting dose of 10 mg/kg per day to 76 recipients of allogeneic HSCT, with subsequent dose adjustments based on efficacy and safety. Deferasirox was initiated at a median of 168 days after HSCT, with 84% of patients still on immunosuppression. Baseline serum ferritin declined from 2045 to 957 ng/mL. Deferasirox induced a negative iron balance in 84% of patients. Hemoglobin increased in the first 3 months, and trough serum cyclosporine levels were stable. Median exposure was 330 days, with a median compliance rate of 480%. The most common investigator-reported drug-related adverse events (AEs) were increased blood creatinine (26.5%), nausea (9.0%) and abdominal discomfort (8.3%). Fifty-four (71.1%) patients experienced drug-related AEs, which occasionally resulted in discontinuation (gastrointestinal (n = 6), skin (n = 3), elevated transaminases (n = 1) and creatinine (n = 1)). The incidence of AEs appeared to be dose related, with 7.5 mg/kg per day being the best-tolerated dose. Low-dose deferasirox is an effective chelation therapy after allogeneic HSCT, with a manageable safety profile, even in patients receiving cyclosporine.

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“…Although improvement of the outcome has been achieved in recent decades via advances in many procedures, such as the prevention of graft-versus-host disease (GVHD), infectious complications remain an important contributor to transplant-related mortality [1,2]. It has recently been reported that iron overload increases the risk of veno-occlusive disease, hepatic dysfunction, and infections after transplantation [3]. It has also been shown that elevated serum levels of pre-transplant ferritin, which is a reliable marker of iron overload, are associated with increased nonrelapse mortality in patients having undergone allo-HSCT [4][5][6].…”

mentioning

confidence: 99%

Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation

Şıvgın

Baldane²,

Kaynar³

et al. 2012

neo

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Iron overload increases the risk of infections, veno-occlusive disease and hepatic dysfunction in post-transplant period. Our objective was to investigate the association of pre-transplant ferritin levels with complications and survival after allogeneic hematopoietic stem cell transplantation (alloHSCT).We retrospectively analysed 84 patients' data who had undergone allogeneic HSCT into two groups: patients with a serum ferritin level≥1000ng/ml, and patients with <1000 ng/ml at the time of HSCT.Cox-regression analysis showed that pre-transplant serum ferritin levels were significantly higher in patients who had at least one infectious event compared with those who had no any infectious event in the post-transplant 100 days (p<0.023). Overall survival (OS) and disease-free survival (DFS) rates were significantly higher in patients with a time-to-tx interval <12 months compared with group time-to-tx interval>12 months (p=0.002 and p=0.008 respectively). A higher risk of death was observed in high-ferritin group (hazard ratio=2.27, CI:1.01-5.09, p=0.023 for OS and hazard ratio=2.49, CI:1.12-5.53 p=0.039 for DFS). No significant effect on OS and DFS among groups was observed for variables conditioning regimen, gender and diagnosis. Acute GVHD was more common in patients with a ferritin level ≥1000 ng /mL, but this was not statistically significant (p>0.05). There was no statistical significance in both groups (ferritin≥1000ng /mL and ferritin<1000ng/mL) for relapse rates (p>0.05). Platelet and neutrophil engaftment day was not found statistically significant compared with both groups (p=0.273 and p=0.882, respectively).Pre-transplant ferritin levels may predict poor outcomes in patients who had undergone allogeneic hematopoietic stem cell transplantation.

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Iron overload in hematopoietic cell transplantation

Cited by 128 publications

References 67 publications

Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation

Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation

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Iron overload in hematopoietic cell transplantation

Cited by 128 publications

References 67 publications

Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation

Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation

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Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation