Quantification by magnetic resonance imaging and liver consequences of post-transfusional iron overload alone in long-term survivors after allogeneic hematopoietic stem cell transplantation

Rosé, Christian; Ernst, Olivier; Hecquet, B; Maboudou, Patrice; Renom, Pascale; Noel, Marie Pierre; Yakoub-Agha, Ibrahim; Bauters, F; Jouet, Jean Pierre

doi:10.3324/haematol.11063

Cited by 51 publications

(31 citation statements)

References 16 publications

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“…The median LIC was 7.7 mg per gram, dry weight, and LIC of 45.6 mg per gram was present in 40% patients. In a cross-sectional study in allogeneic HCT survivors (median followup 9 years) conducted by Rose et al, 30 38/65 (58%) patients had above normal ferritin. Increased LIC (median 117 mmol/g (B6.5 mg per gram), dry weight) was seen in 31/32 patients with elevated ferritin who underwent a T2* MRI of the liver.…”

Section: -31mentioning

confidence: 94%

Iron overload in hematopoietic cell transplantation

Majhail

Lazarus

Burns

2008

Bone Marrow Transplant

124

116

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Section: -31mentioning

confidence: 94%

Iron overload in hematopoietic cell transplantation

Majhail

Lazarus

Burns

2008

Bone Marrow Transplant

124

116

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“…[70][71][72] In heavily transfused patients (eg, thalassemia, myelodysplastic syndrome, severe aplastic anemia, poor red cell engraftment), assessment of iron overload should occur periodically. Ferritin is the most sensitive screening test, although it may be elevated because of hepatic inflammation or as an acute phase reactant.…”

Section: Iron Overloadmentioning

confidence: 99%

How I treat late effects in adults after allogeneic stem cell transplantation

Savani

Griffith

Jagasia

et al. 2011

Blood

104

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More than 25 000 allogeneic hematopoietic stem cell transplantations (allo-HCTs) are expected to be performed worldwide in 2010, a number that has been increasing yearly. With broadening indications, more options for allo-HCT, and improvement in survival, by 2020 there may be up to half a million long-term survivors after allo-HCT worldwide. These patients have increased risks for various late complications, which can cause morbidity and mortality. Most long-term survivors return to the care of their local hematologists/oncologists or primary care physicians, who may not be familiar with specialized monitoring recommendations for this patient population. The purpose of this article is to describe practical approaches to screening for and managing these late effects, with the goal of reducing preventable morbidity and mortality associated with allo-HCT. (Blood. 2011;117(11):3002-3009) IntroductionSince the first 3 cases of successful allogeneic stem cell transplantation (allo-HCT) in 1968, the number of allo-HCTs performed annually has increased steadily over the past 3 decades. [1][2][3][4] Since 2007, more allo-HCT procedures have been performed using alternative donor stem cell sources, such as volunteer unrelated donors or cord blood than related donors. [3][4][5] With less early mortality and more widespread use of HCT, the number of long-term survivors will continue to grow. Yet, among long-term survivors after allo-HCT, mortality rates are 4-to 9-fold higher than observed in an age-adjusted general population for at least 30 years after HCT, yielding an estimated 30% lower life expectancy compared with someone who has not been transplanted. Among long-term survivors, the most common causes of excess deaths other than recurrent malignancy are chronic graft-versus-host disease (GVHD), infections, second malignancies, respiratory diseases, and cardiovascular disease (CVD). [6][7][8][9][10][11] This article summarizes the medical late effects observed in long-term allo-HCT survivors to frame our recommendations for evaluation and management. Given that there are no randomized trials testing diagnostic and treatment approaches for late effects within the HCT population and only limited published guidelines, we turned to general medicine studies for guidance, augmented by our personal experiences. Therefore, this article offers practical advice and outlines our personal approaches in monitoring longterm survivors after allo-HCT. Management of chronic GVHD is beyond the scope of this article and is often managed in conjunction with transplantation physicians. 12 Second malignanciesAfter allo-HCT, survivors have an increased risk of developing new solid cancers, with the cumulative incidence ranging from 2% to 6% at 10 years after transplantation. [13][14][15][16][17] A study of 28 874 allo-HCT survivors published in 2009 reported that new solid cancers developed at twice the rate expected in the general population, 13 with the risk increasing over time, reaching 3-fold among patients followed for 15 years or more...

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“…Sixty-five of 104 patients survived beyond four years post-SCT, of whom 38 (58%) had an elevated SF and 31 of 32 had increased LIC by MRI. 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%

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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Quantification by magnetic resonance imaging and liver consequences of post-transfusional iron overload alone in long-term survivors after allogeneic hematopoietic stem cell transplantation

Cited by 51 publications

References 16 publications

Iron overload in hematopoietic cell transplantation

Iron overload in hematopoietic cell transplantation

How I treat late effects in adults after allogeneic stem cell transplantation

Iron overload in myelodysplastic syndromes (MDS)

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