Effect of iron overload and iron-chelating therapy on allogeneic hematopoietic SCT in children

Lee, J W; Kang, Hyoung Jin; Kim, E K; Kim, H; Shin, Hee Young; Ahn, Hyo Seop

doi:10.1038/bmt.2009.88

Cited by 78 publications

(66 citation statements)

References 14 publications

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“…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. 8 Hence, lowering ferritin after HSCT through phlebotomy 10,[14][15][16][17] and/or iron chelation 15,[17][18][19][20][21] seems rational, although the impact on survival is not yet known and needs to be studied in controlled trials.…”

Section: Introductionmentioning

confidence: 70%

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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Section: Introductionmentioning

confidence: 70%

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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“…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]. The pathogenetic mechanisms for iron overload in hematological malignancies are: prolonged dyserythropoiesis, hemolysis, increased intestinal iron absorption, and multiple red blood cell transfusions [7].…”

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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“…Przed rozpoczęciem leczenia wskazane jest wykonanie badań okulistycznego i audiometrycznego. Do najczęstszych działań niepożądanych należą: odczyny skórne w miejscu podania leku (rumień, pokrzywka, świąd), zawroty głowy, drgawki, nudności, wymioty, bóle brzucha, uszkodzenia siatkówki i zaburzenia widzenia, powstanie zaćmy, uszkodzenie słuchu, hipotonia, niemiarowość serca, a także zaburzenia wzrostu u dzieci [33]. Dlatego, gdy deferoksaminę stosuje się u dzieci, konieczne są regularne kontrole wzrostu -co 3 miesiące.…”

Section: Deferoksaminaunclassified

“…Należy zwrócić uwagę, że wiele danych dotyczących IO pochodzi z populacji chorych na talasemie i są one ekstrapolowane na populacje innych chorych [33]. W randomizowanym badaniu, przeprowadzonym wśród dzieci z TDT, porównywano deferoksaminę z placebo, uzyskując zmniejszenie wartości LIC do 25,9 mg/g suchej tkanki wątroby w porównaniu z 42,2 mg/g w grupie kontrolnej [60].…”

Section: Monoterapia Chelatorami żElaza a Leczenie Skojarzoneunclassified

Znaczenie terapii chelatującej u pacjentów z przeładowaniem żelaza w wyniku częstych transfuzji krwi

Dwilewicz‐Trojaczek¹,

Waszczuk‐Gajda²

2016

Hematologia

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Effect of iron overload and iron-chelating therapy on allogeneic hematopoietic SCT in children

Cited by 78 publications

References 14 publications

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

Znaczenie terapii chelatującej u pacjentów z przeładowaniem żelaza w wyniku częstych transfuzji krwi

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Effect of iron overload and iron-chelating therapy on allogeneic hematopoietic SCT in children

Cited by 78 publications

References 14 publications

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

Znaczenie terapii chelatującej u pacjentów z przeładowaniem żelaza w wyniku częstych transfuzji krwi

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