Prognostic Impact of Posttransplantation Iron Overload after Allogeneic Stem Cell Transplantation

Meyer, Sara C.; O'Meara, Alix; Buser, Andreas; Thewis, André; Passweg, Jakob; Stangel, Martin

doi:10.1016/j.bbmt.2012.10.012

Cited by 53 publications

(58 citation statements)

References 11 publications

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“…The authors concluded that IOL occurs in a sizeable proportion of SCT patients, persists long term, and organ function may be affected [56]. If not quantified by MRI, the incidence of IOL in the context of allo SCT for MDS appears to be more frequent in the early post-transplant phase and to decrease over time, suggesting that confounding factors become less prevalent over time [57].…”

Section: Iron Overload and Allogeneic Stem Cell Transplantation (Sct)mentioning

confidence: 99%

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Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

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Section: Iron Overload and Allogeneic Stem Cell Transplantation (Sct)mentioning

confidence: 99%

“…(2) Even if IOL is assessed by MRI to measure liver iron content, results regarding the prognostic impact of IOL are not consistent [57][58][59][60]. Armand et al concluded that the results presented in their meta-analysis should not be interpreted to imply that iron is irrelevant in HSCT.…”

Section: Iron Overload and Allogeneic Stem Cell Transplantation (Sct)mentioning

confidence: 99%

Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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“…[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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“…1 Little is known of the effects of iron overload on hematopoietic recovery after transplant. In fact, several patients present impaired recovery of hemopoiesis after transplant, with transfusion dependence and/or neutropenia and thrombocytopenia.…”

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confidence: 99%