scholarly journals Iron overload‐related heart failure in a patient with transfusion‐dependent myelodysplastic syndrome reversed by intensive combined chelation therapy

2015 ◽  
Vol 3 (11) ◽  
pp. 952-954 ◽  
Author(s):  
Valeria Pinto ◽  
Manuela Balocco ◽  
Ilaria Ambaglio ◽  
Giorgio Derchi ◽  
Luca Malcovati ◽  
...  
Keyword(s):  
Heart Failure ◽  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Chelation Therapy

scholarly journals The impact of chelation therapy on survival in transfusional iron overload: a meta-analysis of myelodysplastic syndrome

2014 ◽  
Vol 167 (5) ◽  
pp. 720-723 ◽  
Author(s):  
Arch G. Mainous ◽  
Rebecca J. Tanner ◽  
Mary M. Hulihan ◽  
Mirna Amaya ◽  
Thomas D. Coates
Keyword(s):  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Meta Analysis ◽  
The Impact

scholarly journals A case of transfusion independence in a patient with myelodysplastic syndrome using deferasirox, sustained for two years after stopping therapy

2015 ◽  
Vol 22 (2) ◽  
pp. 128 ◽  
Author(s):  
D. Sanford ◽  
C.C. Hsia
Keyword(s):  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Red Blood Cell Transfusion ◽  
Transfusion Independence ◽  
Clinical Complications ◽  
Increased Risk ◽  
History Of

Patients with myelodysplastic syndrome (mds) experience clinical complications related to progressive marrow failure and have an increased risk of developing acute myeloid leukemia. Frequent red blood cell transfusion can lead to clinical iron overload and is associated with decreased survival in mds patients. Iron chelation therapy reduces markers of iron overload and prevents end-organ damage.Here, we present the case of a patient with lowrisk mds with transfusional iron overload. He was treated for 2 years with an oral iron chelator, deferasirox, and after 12 months of treatment, he experienced a hemoglobin increase of more than 50 g/L, becoming transfusion-independent. He has remained transfusion-independent, with a normal hemoglobin level, for more than 2 years since stopping chelation therapy. Hematologic and erythroid responses have previously been reported in mds patients treated with iron chelation. The durability of our patient’sresponse suggests that iron chelation might alter the natural history of mds in some patients.

Cardiac Iron Overload Causes Clinically Evident Heart Failure and Arrhythmia in Sickle Cell Anemia Patients: Evidence From Three Cases

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4846-4846
Author(s):  
Bhakti P. Mehta ◽  
Vasilios Berdoukas ◽  
Mammen Puliyel ◽  
Adam Bush ◽  
Thomas Hofstra ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Overload ◽  
Sickle Cell ◽  
Research Funding ◽  
Chelation Therapy ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Cardiac Iron Overload ◽  
Clinical Heart Failure ◽  
Symptoms And Signs

Abstract Abstract 4846 Transfusional iron overload is associated with poor outcomes in sickle cell disease (SCD). Unlike in thalassemia major (TM), there is no evidence that the iron overload per se causes morbidity in SCD. We present two patients with clear evidence of heart failure and arrhythmia secondary to transfusion induced cardiac iron overload, whose symptoms and signs completely resolved after a short period of intensive iron chelation. We studied 134 patients with SCD with magnetic resonance imaging (MRI). Over 50% of patients with TM and 70% of patients with transfusion dependent Diamond Blackfan Anemia demonstrate cardiac iron overload. We reviewed 472 MRIs in 134 patients with SCD. The median liver iron concentration (LIC) was 10.2 mg/g dry weight (dw). Ten percent of the patients had liver iron > 35mg/g dw. Three (2.2%) demonstrated cardiac iron overload. Patient 1 is now 27 years old and began transfusions at the age of 15 years because of pulmonary hypertension. The first MRI performed at the age of 22 years showed LIC >50 mg/g dw and a cardiac R2* of 128 sec−1 (T2* 7.8 ms) that indicates severe cardiac iron load. At this time she was changed from deferasirox to continuous infusion of desferrioxamine. After 6 months the LIC was 47 mg/g dw and her cardiac R2* was 123sec−1 (T2* 8.1ms). She had dyspnea on mild exertion, ankle edema, and orthopnea. Her left ventricular ejection fraction (LVEF) by MRI at that time was 45%. She started intensive chelation therapy with deferiprone (on compassionate basis) 100mg/kg/day and deferasirox 40mg/kg/day. Her symptoms and signs of clinical heart failure resolved within two months. She remains asymptomatic. After 7 months cardiac R2* is 88 sec−1 (T2*11.3ms) with an LVEF of 55% and LIC of 36 mg/g dw. Patient 2 is now 32 years of age. She started regular blood transfusions at the age of 9 years. Her first MRI at the age of 27 years showed a LIC of >60 mg/g dw and no evidence of cardiac iron overload with a cardiac R2* of 29 sec−1(T2* 34.9ms) with an LVEF of 61%. After 2.5 years her cardiac R2* was 68 sec−1 (T2* 14.7 ms) with an LVEF of 65.7% and 18 months later it was 123 sec−1(T2* 8.1 ms) with an LVEF of 72%. She developed significant arrhythmias coincident with her rapid cardiac iron loading. She was started on compassionate use deferiprone and deferoxamine, with which she is poorly compliant. Repeat cardiac MRI showed a worsening of cardiac iron with R2* of 204 sec−1 (T2* 4.9ms) after 8 months with an improved LVEF of 72%. She currently continues of her regular transfusions and deferiprone and is awaiting repeat MRI. Her LVEF improved while on the chelation therapy despite the deterioration in her cardiac iron content. This is consistent with our observation that LVEF tends to improve even with intermittent chelation although the cardiac iron may not decrease. Patient 3 died of numerous complications of SCD at the age of 19 years. She had started transfusions at the age of 10 years, because of a cerebrovascular accident. At the age of 14 years her first abdominal MRI demonstrated a LIC of 12.8 mg/g dw. She had her first cardiac MRI at the age of 16 years which showed no evidence of cardiac iron with a R2* of 30 sec−1 (T2* 32.7ms), which worsened to 57 (T2* 17.4ms) at the age of 17, reflecting a small but rapid increase in cardiac iron. Patient 1 and 2 demonstrate that transfusional iron overload can directly cause life threatening complications in patients with SCD. Patient 1 in particular, was in overt clinical heart failure that responded dramatically to intensification of chelation therapy. These data underscore the importance of direct measurement of tissue iron concentrations and points out that though uncommon, cardiac iron overload can occur in patients with sickle cell anemia with serious consequences. Disclosures: Berdoukas: ApoPharma Inc.: Consultancy. Carson:ApoPharma Inc.: Honoraria; Novartis Inc: Speakers Bureau. Wood:Cooleys Anemia Foundation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ferrokin Biosciences: Consultancy; Novartis: Research Funding. Coates:Novartis Inc: Speakers Bureau.

4326Reduction of cardiac outcomes in thalassemia major thanks to a ten-year national Italian networking

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Meloni ◽  
L Pistoia ◽  
N Giunta ◽  
N Schicchi ◽  
P Giuliano ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Overload ◽  
Cause Of Death ◽  
Chelation Therapy ◽  
Thalassemia Major ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Cardiac Iron ◽  
Cardiac Outcomes ◽  
Number Of Patients

Abstract Introduction The MIOT (Myocardial Iron Overload in Thalassemia) Network was a network of thalassemia and CMR centers built in 2006 in order to assure homogeneous and standardized cardiac iron overload assessment for a significant number of patients. Purpose We describe the impact of this ten-year Network on cardiac iron, complications and deaths in patients with thalassemia major (TM). Methods 1746 TM patients (911 F; age 31.17±9.09 yrs) were enrolled in the MIOT Network. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2* technique. Biventricular function was quantified by cine images. Results 1392 TM patients performed an end-of-study CMR. At the last CMR significantly higher global heart T2* values (35.44±10.69 ms vs 29.16±12.02 ms; P<0.0001) and a significant lower number of patients with global heart T2*<20 ms (26.3% vs 12.0%; P<0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2*≥20 ms), heterogeneous MIO and global heart T2*≥20 ms, heterogeneous MIO and global heart T2*<20 ms, and homogeneous MIO (all T2*<20 ms). At the last CMR a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were found (Figure 1). In patients with global heart T2*<20 ms a significant increase in left ventricular ejection fraction (EF) (difference: 3.2±8.5%, P<0.0001) as well as in right ventricular EF (difference: 1.2±8.9%, P=0.002) were detected. Based on CMR results the 75% of the patients changed the chelation therapy. At the last CMR the percentage of patients with an excellent/good compliance was significantly higher (94.8% vs 92.2%%; P<0.0001). The complete history of cardiac complications-CC (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, peripheral vascular disease) was present for 1062 patients. Out of the 1001 patients with resolved CC or without CC before the enrolment in the project, the 6.6% had a CC before the enrolment in the project. During the study, the frequency of CC was 4.4%, significantly lower (P=0.023). In particular, the frequency of heart failure (HF) was significantly lower (3.5% vs 0.8%, P<0.0001). Forty-six patients died during the study. HF continues to be the leading cause of death (30.4% of all causes), but there was a consistent decline in HF mortality rate, that was 60.2% in an Italian study dated 2004. No patients died for arrhythmias while cancer was the second leading cause of death. Conclusion Over a period of 10 years, the continuous monitoring of cardiac iron levels and a tailored chelation therapy allowed a reduction of MIO in the 70% of patients, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. So, a national networking was effective in improving the care and reducing cardiac outcomes of TM patients.

Clinical Relevance of Anemia and Transfusion Iron Overload in Myelodysplastic Syndromes

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 166-175 ◽  
Author(s):  
Mario Cazzola ◽  
Matteo G. Della Porta ◽  
Luca Malcovati
Keyword(s):  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Negative Impact ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Thalassemia Major ◽  
Suppressive Effect ◽  
Clinical Consequences ◽  
Production Body

AbstractMost patients with myelodysplastic syndrome eventually become dependent on regular red cell transfusions. This dependency has a negative impact on clinical outcome, primarily because it may be associated with more severe marrow failure. In addition, however, transfusion dependency may involve clinical consequences of chronic anemia and iron overload. Although transfusion iron is primarily taken up by the reticuloendothelial cells, the metal is later redistributed to parenchymal cells. This redistribution is modulated by several factors, including the degree of ineffective erythropoiesis through its suppressive effect on hepcidin production. Body iron status is routinely assessed by serum ferritin and transferrin saturation, but there is a need of reliable tools for locating iron accumulation in patients. Magnetic resonance imaging T2* provides a non-invasive method for detecting and quantifying both liver and myocardial iron overload. Clinical consequences of parenchymal iron overload have been reported not only in thalassemia major, but also in patients with myelodysplastic syndrome. Transfusion-dependent patients with isolated erythroid dysplasia and low risk of leukemic evolution are more likely to develop parenchymal iron overload and its toxicity, and therefore may benefit from chelation therapy. There may also be a benefit of chelation therapy in patients with transfusion iron overload undergoing allogeneic stem cell transplantation. Deferoxamine and deferasirox are currently available for treatment of transfusion iron overload in patients with myelodysplastic syndrome.

Acute Kidney Injury in Patients Receiving Subcutaneous Deferoxamine Therapy.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3851-3851
Author(s):  
Arjuna Ponnampalam ◽  
Donald S Houston
Keyword(s):  
Acute Kidney Injury ◽  
Renal Impairment ◽  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Bolus Injection ◽  
Chelation Therapy ◽  
Kidney Injury ◽  
Refractory Anemia ◽  
The Third ◽  
Intermittent Bolus

Abstract Iron chelation is an important modality in treating patients with iron overload syndromes to minimize end-organ damage. The greatest experience has been in young patients with thalassemia, but there is growing use of chelation therapy in patients with acquired transfusion-dependent disorders such as myelodysplastic syndrome. Deferoxamine is a clinically proven and effective therapy for long term chelation, but the standard mode of administration by subcutaneous pump-driven infusion is burdensome for patients and leads to poor adherence. Intermittent bolus injection (1g in 10ml of water injected subcutaneously twice daily) has been advocated as an alternative protocol that may facilitate compliance. Acute kidney injury has been described previously in patients receiving high dose intravenous deferoxamine, but not in patients receiving subcutaneous therapy, and nephrotoxicity is not listed as an adverse effect in the product monograph. Here we report a series of three patients who developed acute kidney injury when receiving subcutaneous deferoxamine by intermittent bolus injection. CASES: All three patients were elderly adults. The first was a 64 year old man who developed iron overload secondary to hemoglobin H disease, the second was a 78 year old woman with transfusion-dependent myelodysplastic syndrome (refractory anemia with ring sideroblasts), and the third was an 83 year old man with transfusion-dependent smoldering multiple myeloma. These patients had preexisting mild renal impairment: the first was a kidney transplant recipient taking cyclosporine, the second had a prior nephrectomy for renal carcinoma, and the third had longstanding renal impairment from renovascular disease. All three patients had resolution of their acute kidney injury on discontinuation of therapy and have had stable creatinine values subsequently. Rechallenge with deferoxamine led again to a reversible rise in creatinine in the first patient. The most striking effect was in the second patient: her creatinine level rose from a baseline of 154μmol/l to 280μmol/l one month after starting deferoxamine, and fell to 138μmol/l two weeks after discontinuing the drug. DISCUSSION: We conclude that renal dysfunction can be an important side effect of deferoxamine chelation. The toxicity appears to be reversible on discontinuation of therapy. Older patients and patients with pre-existing renal impairment may be more susceptible to this effect, and subcutaneous bolus dosing may increase the risk, possibly due to higher peak drug levels. Careful monitoring of creatinine values and minimization of other nephrotoxic agents is appropriate and prudent when managing iron overload syndromes with deferoxamine chelation therapy.

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