Iron Overload in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation: Quantification of Iron Burden by a Superconducting Quantum Interference Device (SQUID) and Therapeutic Effectiveness of Phlebotomy

Busca, Alessandro; Falda, Michele; Manzini, Paola; D’Antico, Sergio; Valfrè, Adriano; Locatelli, Franco; Calabrese, R.; Chiappella, Annalisa; D’Ardia, Stefano; Longo, Filomena; Piga, Antonio

doi:10.1016/j.bbmt.2009.09.011

Cited by 55 publications

(42 citation statements)

References 31 publications

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“…67 Iron overload has also been associated with the risk of invasive fungal infections after allogeneic HCT. [77][78][79][80] Finally, increasing infectious risk may be one of the mechanisms whereby iron overload negatively impacts on the prognosis of allogeneic HCT in patients with MDS. 74,81,82 Whether iron chelation could decrease the risk of infection in MDS has not been demonstrated.…”

Section: Role Of Iron Overload In the Risk Of Infectionmentioning

confidence: 99%

Infections in myelodysplastic syndromes

et al. 2012

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Myelodysplastic syndromes are associated with a risk of severe infections. While neutropenia is likely to be the main predisposing factor, several other immune defects have been reported, including impaired neutrophil function, B-, T-and NK-cell defects and the possible consequences of iron overload due to red blood cell transfusions. The advanced age of most patients, their frequent comorbidities, and the fact that drugs such as hypomethylating agents and lenalidomide, which are effective in myelodysplastic syndromes but can transiently worsen neutropenia, may increase the risk of infection and their severity in this context. The majority of infections in myelodysplastic syndromes are bacterial, while the incidence of fungal infections is not well known and viral infections seem to be rare. No prophylactic measures against infections have demonstrated efficacy in myelodysplastic syndromes. However, pending more data, we propose here some recommendations for the management of patients with myelodysplastic syndromes. In the future, an important contribution can be made by prospective trials testing the efficacy of prophylactic and therapeutic approaches to infection in these patients, especially in the context of the new drugs available for myelodysplastic syndromes. ABSTRACTand respective bacterial, fungal, and viral causes of infection in MDS. Most of these data are retrospective. Some are compromised by inconsistencies in the definition of the infectious events or, although taken from therapeutic trials, may be biased by patient eligibility criteria. In a recent US retrospective series of 273 untreated low-or intermediate-1 risk MDS patients who died in the period from 1980 to 2004, infection was the primary cause of death, accounting for 38% of the total, followed by AML transformation (15%) and hemorrhage (13%).9 Pneumonia was the most common infection, responsible for 40% of infectious deaths. Infection, mostly of a bacterial origin, was microbiologically documented in 30% of the cases of pneumonia in these MDS patients. As this study covered three decades, it was possible to show a significant decrease in the incidence of infectious deaths over time, likely attributable to improved supportive care. Another US survey of the Medicare population (an insurance covering more than 97% of all US citizens aged 65 years or over) indicated that, in a population of 1.3 million people over the age of 65 years followed between the years 2003 and 2005, patients with MDS had a higher prevalence of infections than the non-MDS Medicare population (22.5% vs. 6.

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Section: Role Of Iron Overload In the Risk Of Infectionmentioning

confidence: 99%

Infections in myelodysplastic syndromes

et al. 2012

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“…Nineteen of the 24 eligible patients (defined by the absence of disease recurrence and/or poor performance status) for iron-depletion therapy underwent regular phlebotomy (at 7-14-day interval until a serum ferritin level <500 ng/ml) and 13 completed the program in a median of 287 days, reaching the target of a ferritin level <500 ng/ml. LIC was significantly reduced in 8 of the 9 patients who were revaluated by SQUID at the end of the phlebotomy program [57].…”

Section: Statementmentioning

confidence: 99%

“…Busca et al [57] retrospectively analyzed for the presence of iron overload a series of 102 consecutive patients who underwent allo-SCT (including 17 subjects affected with MDS). Nineteen of the 24 eligible patients (defined by the absence of disease recurrence and/or poor performance status) for iron-depletion therapy underwent regular phlebotomy (at 7-14-day interval until a serum ferritin level <500 ng/ml) and 13 completed the program in a median of 287 days, reaching the target of a ferritin level <500 ng/ml.…”

Section: Statementmentioning

confidence: 99%

Iron overload and iron chelation therapy in patients with myelodysplastic syndrome treated by allogeneic stem‐cell transplantation: Report from the working conference on iron chelation of the Gruppo Italiano Trapianto di Midollo Osseo

Alessandrino

Angelucci²,

Cazzola

et al. 2011

American J Hematol

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“…Phlebotomy is generally well tolerated with minimal toxicities and has been used in HSCT patients successfully. 10 We undertook a prospective cohort study in HSCT patients with iron overload to evaluate the safety, feasibility and efficacy of decreasing total body iron by phlebotomy.Institutional Research Ethics Board approval was obtained to perform this study and all patients provided informed consent. We enrolled patients who were between the ages of 18 and 65 and who were at least 60 days after HSCT.…”

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confidence: 99%

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confidence: 99%

A prospective cohort study of the feasibility and efficacy of iron reduction by phlebotomy in recipients of hematopoietic SCT

Clarke

Ridler

et al. 2014

Bone Marrow Transplant

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Transfusional iron overload is common in hematopoietic SCT (HSCT) patients and is a potential cause of morbidity and mortality. Iron overload, estimated by increased ferritin, appears to be associated with adverse outcomes and decreased survival. [1][2][3][4] There are several unanswered questions in this area. First, it is not clear how to best measure iron overload in these patients. Second, the exact mechanism whereby iron overload causes increased mortality has not been definitively established. Finally, the impact of reducing iron and the best method to achieve iron reduction in these patients are unknown.The simplest method to estimate iron overload is by measurement of serum ferritin. However, this strategy is not specific because ferritin is an acute phase reactant and can be elevated in a variety of inflammatory conditions. 5 In the pre-and posttransplant setting, patients may have an elevated ferritin for reasons other than iron overload. Interestingly, a recent study demonstrated that elevated ferritin was associated with decreased survival, but there was no survival impact of iron overload as measured by magnetic resonance imaging (MRI). 6 A meta-analysis also found that there was no association between the iron overload measured by MRI and whilst a serum ferritin of 41000 ng/mL was associated with increased mortality, an even higher ferritin of 42500 ng/mL was not. 7 The 'gold standard' for the measurement of total body iron is the liver biopsy stained with Perls' Prussian blue 8 but MRI is increasingly used to measure the liver iron content and correlates with the liver biopsy. 9 There are two approaches to remove excess iron: phlebotomy and iron chelation. Phlebotomy is generally well tolerated with minimal toxicities and has been used in HSCT patients successfully. 10 We undertook a prospective cohort study in HSCT patients with iron overload to evaluate the safety, feasibility and efficacy of decreasing total body iron by phlebotomy.Institutional Research Ethics Board approval was obtained to perform this study and all patients provided informed consent. We enrolled patients who were between the ages of 18 and 65 and who were at least 60 days after HSCT. Patients were eligible for the study if they were red cell transfusion independent and had a serum ferritin of at least 1000 μg/L at study entry. Patients underwent phlebotomy of 500 mL of whole blood for 12 procedures. Initially, phlebotomies were done monthly. If the ferritin remained significantly elevated (41000 μg/L) after six phlebotomies, the frequency of phlebotomies was increased to weekly as tolerated. Complete blood count was assessed before each phlebotomy and if the Hb level was o 100 g/L, the phlebotomy was not performed. Iron stores were estimated biochemically by measuring serum ferritin and transferrin saturation levels in each patient before the start of phlebotomy and at 6 and 12 months. Total body iron was estimated from hepatic iron concentration as measured by MRI (signal intensity ratio method) at the same time points. Ser...

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Iron Overload in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation: Quantification of Iron Burden by a Superconducting Quantum Interference Device (SQUID) and Therapeutic Effectiveness of Phlebotomy

Cited by 55 publications

References 31 publications

Infections in myelodysplastic syndromes

Infections in myelodysplastic syndromes

Iron overload and iron chelation therapy in patients with myelodysplastic syndrome treated by allogeneic stem‐cell transplantation: Report from the working conference on iron chelation of the Gruppo Italiano Trapianto di Midollo Osseo

A prospective cohort study of the feasibility and efficacy of iron reduction by phlebotomy in recipients of hematopoietic SCT

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