A Prospective Study of Iron Overload in Patients Undergoing Ablative Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3332-3332
Author(s):  
Philippe Armand ◽  
Joanna Rhodes ◽  
Haesook Kim ◽  
Corey Cutler ◽  
Vincent T. Ho ◽  
...  
Keyword(s):  
Iron Overload ◽  
Prospective Study ◽  
Serum Ferritin ◽  
Hepatic Iron ◽  
Prior Chemotherapy ◽  
Cardiac Iron ◽  
Hepatic Iron Overload ◽  
Cardiac Iron Overload ◽  
A Prospective Study ◽  
Transfusion History

Abstract Abstract 3332 Poster Board III-220 Introduction Iron overload is a recently recognized problem for patients undergoing hematopoietic stem cell transplantation (HSCT). Hyperferritinemia is common and is associated with significantly increased treatment-related mortality (TRM) and poorer overall survival after HSCT. However, serum ferritin may be a poor surrogate for total body iron burden, and no prospective study of parenchymal iron overload has yet been reported. We initiated a prospective study of adult patients with acute leukemia or myelodysplastic syndrome (MDS) undergoing myeloablative HSCT, in order to estimate the prevalence of iron overload in this population. We measured pre-HSCT serum ferritin, C-reactive protein (CRP), iron, total iron binding capacity, and genotyped patients for HFE mutations. All patients also underwent liver and cardiac MRI with measurement of T2*, from which liver iron content (LIC) and cardiac iron loading were inferred. Results 41 of 45 planned patients have been enrolled to date. Median age was 46 years (range, 18-63). 24 patients had AML, 11 had ALL, and 6 had MDS. They had received a median of 2 prior chemotherapy courses (range, 0-6). Among the 39 patients with available transfusion history, the median number of prior RBC transfusions was 19 (range, 0-59). 88% of patients had a pre-HSCT serum ferritin above normal; the median value was 1432 (range, 20-6989). Higher ferritin values were associated with more advanced disease stage, number of prior chemotherapy regimens, and number of transfusions. The median LIC was 3 g/g dry weight (g/gdw) (range, 0.6-12.9). 85% of patients had an LIC above the upper limit of normal (1.8 g/gdw), and 17% had an LIC above 7 g/gdw. Only 1 patient had cardiac iron overload (cardiac T2*<20 msec). Pre-HSCT LIC correlated best with serum ferritin (r=0.7), although it also correlated with transfusion history (r=0.56) and with transferrin saturation (r=0.50). The correlation improved further (r=0.76) when ferritin was divided by log(CRP), when CRP was above normal (see Figure). Median follow-up after HSCT is 4.5 months (range, 0.2-13.5), precluding full analysis of clinical outcomes at this point. Conclusion Hepatic iron overload is very common in patients with acute leukemia or MDS undergoing HSCT, and is strongly correlated with transfusion history. Cardiac iron overload is rare. Pre-HSCT serum ferritin, adjusted for CRP, is a good surrogate marker for hepatic iron overload. This close relationship lends support to prior studies that used serum ferritin to assess the impact of pre-HSCT iron overload on transplantation outcome. Moreover, it provides the basis for the assessment of iron chelation strategies to reduce TRM. Disclosures Armand: Novartis: Consultancy, Research Funding.

scholarly journals A T2* MRI Prospective Survey on Cardiac and Hepatic Iron in Non-Trasfusion-Dependent Thalassemia Intermedia Patients Treated with Desferrioxamine

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4900-4900
Author(s):  
Antonella Meloni ◽  
Aurelio Maggio ◽  
Carlo Cosmi ◽  
Alfonso D'Ambrosio ◽  
Elena Facchini ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Real Life ◽  
Hepatic Iron ◽  
Thalassemia Intermedia ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Hepatic Iron Overload ◽  
Cardiac Iron Overload

Abstract Background. In thalassemia intermedia (TI) patients no observational study prospectively evaluated in the real life the efficacy of the desferrioxamine (DFO) therapy in removing or preventing iron overload from the heart and the liver by T2* Magnetic Resonance Imaging (MRI). The efficacy endpoint of this study is represented by the changes in cardiac T2* and MRI LIC (liver iron concentration) values in non-transfusion dependent (NTD) TI patients after 18 months of desferrioxamine therapy. Methods. Among the 325 TI patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we selected 129 TI patients NTD. We considered 29 patients who had been received DFO alone between the two MRI scans. Cardiac iron overload was assessed by the T2* multiecho technique. Hepatic T2* values were converted into liver iron concentration (LIC) values. Results. Mean age was 39.69 ± 8.12 years and 14 (48.3%) patients were females. Patients started regular chelation therapy at a mean age of 21.92 ± 15.89 years. The mean administered dosage of DFO via subcutaneous route was 38.46 ± 10.27 mg/kg body weight on 3.32 ± 1.54 days/week. The percentage of patients with excellent/good levels of compliance to the chelation treatment was 82.1%. At baseline only one patient showed cardiac iron overload (global heart T2*=15.23 ms) but he recovered at the FU (global heart T2*=26.93 ms). All patients without cardiac iron maintained the same status at the follow-up (FU). Eighteen patients (62.1%) had hepatic iron overload (MRI LIC ≥3 mg/g/dw) at the baseline. For this subgroup, the baseline and the FU LIC values were, respectively, 9.15 ± 7.97 mg/g/dw and 7.41 ± 6.28 mg/g/dw. The reduction in MRI LIC values was not significant (P=0.102). Out of the 11 patients with a baseline MRI LIC <3 mg/g/dw, only one (9.1%) showed hepatic iron at the FU. The Figure shows the evolution of different hepatic iron overload risk classes between the baseline and the FU. Conclusions. In this small population of sporadically or non transfused TI patients, DFO showed 100% efficacy in maintaining a normal global heart T2* value. As regards as the hepatic iron overload, the DFO therapy did not prevent the transition to a worst class in 2 patients. Figure 1 Figure 1. Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

Magnetic Resonance Imaging (MRI) Detection of Iron Overload In Patients with Myelodysplastic Syndrome (MDS)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4960-4960
Author(s):  
Fabio PS Santos ◽  
Claudia Bley ◽  
Ricardo Helman ◽  
Guilherme Fleury Perini ◽  
Iracema Esteves ◽  
...  
Keyword(s):  
Iron Overload ◽  
Transferrin Saturation ◽  
Low Risk ◽  
Refractory Anemia ◽  
Categorical Variables ◽  
Hepatic Iron ◽  
Cardiac Iron ◽  
Hepatic Iron Overload ◽  
Cardiac Iron Overload ◽  
T2 Mri

Abstract Abstract 4960 Introduction: Transfusion dependent anemia and iron overload are associated with reduced survival in patients with MDS. Increased iron absorption at the gastrointestinal tract may also contribute to iron overload. Serum ferritin is the most common method of assessing body iron content, but it can be elevated in patients with inflammatory conditions, and may not correlate with iron overload in specific organs such as the heart. T2* MRI is a non-invasive method for detecting iron overload in patients with transfusion-dependent anemia, and its efficacy has been validated in patients with thalassemia major. There are few studies reporting on the efficacy of T2* MRI for detection of iron overload in patients with MDS. Objective: To evaluate the efficacy of T2* MRI in detection of iron overload in patients with MDS, the prevalence of iron overload in this disease and correlate MRI findings with iron indexes (ferritin, transferrin and non-transferrin bound iron [NTBI]). Methods: Patients with MDS or chronic myelomonocytic leukemia (CMML), independent of transfusion requirements, were recruited into a prospective, single center trial to assess the efficacy of T2* MRI for detection of iron overload in this scenario. Patients receiving iron chelation therapy were excluded. Iron indexes were measured at the time of T2* MRI evaluation. Hepatic iron overload was considered in patients with a hepatic iron concentration (HIC) ≥ 2 g/mg. Cardiac iron overload was considered in patients with a T2* value < 20 milliseconds. Mann-Whitney and Fischer exact tests were used to compare baseline continuous and categorical variables among patients with and without iron overload as assessed by HIC. Correlation between HIC and iron indexes was assessed with Spearman correlation. Results: A total of 37 patients with MDS and one patient with CMML were recruited. Three patients were not evaluated by MRI due to claustrophoby, so 35 patients remain for the analysis. Median age was 68 years (range 18–84). MDS subtypes by the WHO classification include refractory anemia (N=3), refractory anemia with ring sideroblasts (N=5), 5q- syndrome (N=3), refractory cytopenias with multilineage dysplasia (N=13), refractory anemia with excess blasts-I (N=6) and –II (N=3) and unclassifiable MDS (N=1). Information about transfusion requirement was available for 28 patients, and 14 (50%) were transfusion dependent. Twenty-two patients could be classified by the WHO Prognostic Score System (WPSS) and were categorized as very low-risk (N=6), low-risk (N=3), intermediate risk (N=6) and high risk (N=7). Median ferritin, transferrin saturation and NTBI values were 1079.6 ng/mL (range 21.8–12738 ng/mL), 63% (range 6–100%) and 0.34 microM (range 0–12.93 microM), respectively. Median cardiac T2* value was 45.3 ms (range 19.7–70.1 ms), and only one patient had a T2* value indicative of cardiac iron overload. Median HIC value was 3.31 g/mg (range 0.2–9.97 g/mg), and 66% of patients had hepatic iron overload. Patients with hepatic iron overload had higher ferritin levels (1181 ng/mL vs. 131 ng/mL, p=0.007) and transferrin saturation (64% vs. 39%, p=0.02), but no differences in NTBI (0.29 microM vs. 0.22 microM, p=0.42). Patients with elevated HIC had a higher prevalence of transfusion dependency but the difference was not significant (50% vs. 33%, p=0.67). Ferritin levels and transferrin saturation correlated with HIC (r = 0.552, p=0.001 [ferritin]; r = 0.609, p=0.001 [transferrin saturation]). Conclusion: T2* MRI can detect iron overload in patients with MDS. Iron overload in MDS cannot be solely explained by transfusion dependent anemia. The study is currently ongoing and updated results will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The impact of magnetic resonance imaging in the assessment of iron overload in heart and liver in transfusion-dependent thalassemic children: Minia experience

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Ashraf M. El Sherif ◽  
Ahmed S. Ibrahim ◽  
Mohamed A. Elsayed ◽  
Ahmed S. Abdelhakim ◽  
Ahlam M. Ismail
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Deposition ◽  
Hepatic Iron ◽  
Resonance Imaging ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Background Thalassemia is the most prevalent single-gene disorder. Myocardial and hepatic iron depositions lead to complications and eventually death. We aimed to assess the diagnostic efficacy of magnetic resonance imaging T2* (MRI T2*) in quantifying iron overload in liver and heart in transfusion-dependent B-thalassemia major (TDT) children. Methods Prospective clinical study was carried on sixty children diagnosed with TDT. All of them underwent laboratory investigations, including CBC, serum iron, and ferritin levels. MRI T2* of the heart and liver was carried out to measure the iron overload and estimate the left ventricular ejection fraction (LVEF). Results Thirty-eight males and 22 females with TDT with a mean age of 13.23 years were included. Twenty cases (33.3%) had severe liver iron overload, while 36 (60%) had normal cardiac iron. There was a moderate significant negative association between hepatic and cardiac iron deposition (P = 0.03). All cases with severe cardiac iron overload had impaired LVEF below 56%. A non-significant positive association was noticed between cardiac iron deposition and LVEF in T2* (P = 0.08). A moderate negative significant association was detected between hepatic iron deposition and serum ferritin, while a fair negative significant association was found between serum ferritin and cardiac iron deposition with P values of 0.04 and 0.02, respectively. Conclusion MRI T2* is the gold standard for monitoring and follow-up of iron overload in the heart and liver. It should be routinely performed in all TDT children as liver iron, and serum ferritin do not reflect cardiac iron overload.

scholarly journals Plasma level of matrix metalloproteinase-9 in patients with sickle cell disease and its correlation to myocardial iron overload

2020 ◽  
Author(s):  
Tamer Hassan ◽  
Mohamed Badr ◽  
Mohamed Arafa ◽  
Doaa Abdel Rahman ◽  
Manar Fathy ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Plasma Levels ◽  
Restrictive Cardiomyopathy ◽  
Myocardial Iron ◽  
Cell Disease ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Cardiac iron overload is secondary to chronic blood transfusion in patients with sickle cell disease (SCD). Iron overload cardiomyopathy is a restrictive cardiomyopathy associated with systolic and diastolic dysfunction. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling. Many studies offer strong evidence for the role of MMP-9 in LV remodeling. We aimed to detect plasma levels of MMP-9 in patients with SCD and its correlation to myocardial iron overload. A case control study was carried out on 50 patients with SCD and 50 age and sex matched healthy controls. Assessment of cardiac iron overload in patients by MRI T2* was performed. Plasma MMP-9 levels were measured for patients and controls using ELISA. SCD patients had significantly higher levels of MMP-9 than controls. There was highly significant correlation between plasma levels of MMP-9 and serum ferritin. Patients with vaso-occlusive crises (VOC) > 5/year had significantly higher levels of MMP-9 than those with VOC ≤ 5 /year. No significant correlation was found between MMP-9 and cardiac T2*. MMP-9 seems to be a useful marker in SCD patients. Patients with serum ferritin > 1000 ng/ml, recurrent VOC > 5 /year had significantly higher MMP-9 serum levels than others.

Update in Combined Chelation Therapy with Deferoxamine and Deferiprone in Brazilian Patients with Thalassemia Major: Assessment of Three Years

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5415-5415
Author(s):  
Sandra Regina Loggetto ◽  
Mônica Veríssimo ◽  
Antônio Fabron Júnior ◽  
Giorgio Roberto Baldanzi ◽  
Nelson Hamerschlak ◽  
...  
Keyword(s):  
Adverse Events ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Combined Therapy ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Introduction: Cardiac failure is a main cause of morbidity and mortality in patients with thalassemia major (TM) who are receiving regular blood transfusion due to iron overload. So, effective and adequate iron chelation is extremely important. Deferoxamine (DFO), the most widely used iron chelator, has poor compliance. Combined therapy with Deferiprone (DFP) increases chelation efficacy, decreases iron-induced complications, improves compliance increasing survival in thalassemia. Objectives: Assessment of efficacy and safety in combined chelation with DFP and DFO in thalassemic patients with iron overload. Methods and results: We have 50 thalassemia major patients in 4 Brazilian Centers (Boldrini Hospital, Sao Paulo Hematology Center, HEMEPAR and FAMEMA) receiving combined chelation therapy with follow up to three years. DFP (75–100 mg/kg/daily) and DFO (30–60 mg/kg, 4–7 days/week) are being administered during one to three years. Median age of this group is 21,5 y/o (range 8–35), with 48% female. Median age to start regular transfusions was 12 months (range 2–140) and to begin chelation therapy was 57 months (range 17–216). All patients were screened for Hepatitis C and 26% had positive sorology and/or PCR. Statistical analysis were made with Spearman test and Fisher test. All patients, except two, did cardiac and liver MRI in the initial phase of the study, resulting in 60,5% with cardiac iron overload (T2*&lt;20ms), being severe in 31,2%. Assessment of liver iron concentration (LIC) showed 95,7% with liver iron overload (&gt;3ug/g dry weight), being severe in 17,4%. During follow up, only 43 patients (86%) was screened with MRI. From these, 67,4% had cardiac iron overload (severe in 32,5%) and 78,6% had liver iron overload (severe in 11,9%). Mean serum ferritin before and after three years were 3095,7 ±1934,5 ng/ml and 2373,9±1987,6 ng/ml, respectively. Our data showed positive correlation between serum ferritin, LIC and ALT, even in initial data and after combined chelation therapy (p&lt;0,001), but there is no correlation between cardiac T2* and LIC and between cardiac T2* and ferritin. DFP adverse events included 8% agranulocytosis, 22% neutropenia, 20% arthralgia and 38% gastric intolerance. DFO adverse events were 2,6% deafness, 2,0% cataract and 12% growth deficit. Hepatic toxicity was found in 6%, but without necessity to stop treatment. Compliance in this group was excellent in 48%, good in 22% and poor in 30%. Conclusions: This is the first multicenter study to evaluate combined chelation therapy in Brazil based on cardiac MRI and LIC. Most patients had cardiac and hepatic iron overload probably because they began iron chelation lately, due to difficult access to iron chelators in the past. Cardiac iron overload didn’t have correlation with ferritin and LIC and these data need more understanding. Age of initial regular blood transfusion, increased transfusional requirement, inadequate chelation or delayed chelation may play a role in this question. Combined therapy with DFO and DFP is effective to decrease serum ferritin and LIC. Follow up and improving compliance may decrease cardiac iron overload. Adverse events are similar to literature. Combined therapy is safety in TM patients with transfusional iron overload.

Oral Chelator Deferiprone in Adult with Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4615-4615
Author(s):  
Ruben Nzouakou ◽  
Anoosha Habibi ◽  
Ketty Lee ◽  
Alain Luciani ◽  
Jean-François Deux ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Cardiac Iron ◽  
Median Level ◽  
Cardiac Iron Overload ◽  
The Mean

Abstract Abstract 4615 INTRODUCTION Long-term blood transfusion is essential for patients with sickle cell disease (SCD) in case of cerebral vasculopathy, organ dysfunction, leg ulcer, failure or intolerance of hydroxyurea treatment. Secondary iron overload is a factor of morbidity and mortality by organ damage. In practice, three chelators are available: deferoxamine (DFO) which is administrated by subcutaneous infusion and therefore source of poor compliance in SCD. Deferasirox (DFX), the new oral chelator is the first line therapy since 2007. Deferiprone (DFP) is an option when DFX or DFO are contraindicated or inadequate. However, DFP has no approval for SCD. The purpose of this study is to describe the characteristics of SCD patients treated by DFP. METHODOLOGY The patients included in this study arise from the group of the patients with long-term blood transfusion by manual exchange in Henri Mondor's SCD center, and in whom iron overload is treated by DFP. The monitoring of iron overload is obtained by regular serum ferritin level, combined liver and heart MRI. Only one iron measure by MRI is available for each patient throughout the study. RESULTS Nine patients (8 SS and 1 Sβ0thal) are included: 5 men and 4 women. The mean age is 44.2 years (22 to 64 years). The median duration of chronic transfusion is 10 years (4 to 27 years). The average dose of DFP is 68 mg / kg / day (50 to 93 mg / kg / day). The median follow-up under DFP is 30 months (7 to 60 months). The median level of serum ferritin before the initiation of DFP is 5830 μg / l (1800 to 9300 μg / l); and the median level of serum ferritin at the end point is 7940 μg / l (4540 to 11300 μg / l). MRI shows an important hepatic iron overload (up to 320 μmol) in all patients and one cardiac iron overload (T2* = 12 ms). Three patients stopped DFP and switch to deferasirox (DFX) as soon as DFX was available. For the other patients, the reason of prescribing DFP instead of DFX was renal failure in 5 patients and DFX related GI symptoms in one patient. No agranulocytosis is observed. The weekly then monthly monitoring of blood count is insured for all patients. No cytolysis by drug's toxicity is observed, except for one patient with liver transplant and who has an active HCV infection. DISCUSSION Serum ferritin level is the easiest marker of iron overload follow-up, but is subject of important variations due to inflammation, hemolysis, and cytolysis. Indeed, MRI is the only one reliable measure. The evidence of cardiac iron overload is proved in one patient, and confirms the importance of this measure on SCD patients. This motivates the edition of guidelines concerning the prevention and monitoring of iron overload among these patients. The dosage of DFP remains reasonable compared to the mean dosage use in other pathologies. This dosage depends of the degree of iron overload and the individual tolerance. Data are not sufficient at these days to evaluate the efficacy of DFP to reduce or to stabilize the level of iron overload. However, we observe globally a good clinical and biological tolerance, even in patients who have organ transplant and therefore have several concomitant treatments. CONCLUSION DFP in patients with SCD is globally well-tolerated, but its efficiency is not proved yet. Approval of DFP for SCD is needed. As life expectancy improves in SCD, more patients will require long-term transfusion and thus iron chelation therapy. Cardiac Iron overload is possible in patients with SCD. So, it would be systematically looked after. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prospective Changes of Cardiac and Hepatic Iron and Cardiac Function in Low and Intermediate-1 Risk MDS Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1911-1911
Author(s):  
Alessia Pepe ◽  
Antonella Meloni ◽  
Giancarlo Carulli ◽  
Esther Natalie Oliva ◽  
Francesco Arcioni ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Iron Overload ◽  
Myocardial Fibrosis ◽  
Chelation Therapy ◽  
Mean Difference ◽  
Volume Index ◽  
Hepatic Iron ◽  
Cardiac Iron ◽  
Biventricular Function ◽  
Hepatic Iron Overload

Abstract Background: In patients with myelodysplastic syndrome (MDS) no longitudinal studies on myocardial and hepatic iron and on cardiac function and fibrosis are available in literature. So, the aim of our study was to assess the changes in cardiac and hepatic iron overload and the morpho-functional cardiac parameters by Magnetic Resonance Imaging (MRI) in MDS patients enrolled in the MIOMED (Myocardial Iron Overload in MyElodysplastic Diseases) study who performed the follow-up (FU) MRI at 12 months. Methods: MIOMED is an observational, MRI multicentre study in low and intermediate-1 risk MDS patients who have not received regular iron chelation therapy. Out of the 51 MDS patients enrolled, 48 underwent the baseline MRI exam and 28 performed the MRI FU. This analysis was limited to patients who performed both the MRIs. Mean age was 72.8±7.6 years and 8 patients were females. MIO was assessed using a multislice multiecho T2* approach. Hepatic T2* values were assessed in a homogeneous tissue area and converted into liver iron concentration (LIC). Biventricular function parameters were quantified by cine sequences. Myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) acquisitions. Results: The FU MRI was not performed for the following reasons: 4 deaths and 16 patient refusal. At baseline only one patient showed cardiac iron overload (global heart T2*=14.8 ms) but he recovered at the FU (global heart T2*=28.8 ms). He was not transfused. Out of the 27 patients without significant cardiac iron at the baseline, 26 maintained the same status at the FU while one showed cardiac iron (global heart T2*=12.3 ms). Thirteen patients (8 transfusion-dependent - TD) had hepatic iron overload (MRI LIC≥3mg/g/dw) at the baseline.For this subgroup, the baseline and the FU LIC values were, respectively, 14.9±12.0 mg/g/dw and 20.1±16.1 mg/g/dw. The increase in MRI LIC values was not significant (P=0.196). Out of the 11 patients with a baseline MRI LIC<3 mg/g/dw, two (13.3%) showed hepatic iron at the FU. Only one patient was TD but both patients had not received any chelation therapy. Serum ferritin levels were comparable at both the MRIs (923±618 vs 1168±1004 ng/ml; P=0.150). Due mainly to technical reasons, biventricular function was assesses at both baseline and FU MRIs in 22 patients. At baseline 6 patients showed a reduced left ventricular ejection fraction (LVEF) and 4 of them recovered at the FU. All patients had a baseline global heart T2*>20 ms (one with 2 segmental T2* values<20 ms). At baseline 5 patients showed a reduced right ventricular EF (RV EF) and all recovered at the FU. One patient with normal LV EF at baseline showed pathological LV EF at the and 2 patients with normal RV EF at baseline showed reduced RV EF at the FU (one patient suffered from pulmonary hypertension). At the FU we detected a significant increase in the LV end-diastolic volume index (EDVI) (mean difference: 6.5±11.3 ml/m2; P=0.015) as well as in the RV EDVI (mean difference: 7.8±9.3 ml/m2; P=0.002). The change in the LV mass index between the 2 MRIs was not significant. For 18 patients the presence of myocardial fibrosis was investigated at both baseline and FU MRIs, and this subgroup was considered. Eight patients had myocardial fibrosis at the baseline. One patient showed a subendocardial ischemic pattern and seven patients showed a non-ischemic pattern and myocardial fibrosis was detected for all of them also at the FU. At the FU one new occurrence of non-ischemic myocardial fibrosis was detected. Conclusion. The new occurrences of cardiac iron, reduced cardiac function, increased LV and RV EDVI and myocardial fibrosis and the worsening in MRI LIC values suggest the need of performing periodic MRI scans, in order to better manage these patients. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures Oliva: Celgene: Consultancy, Honoraria; Novartis: Consultancy, Speakers Bureau.

From Renal Siderosis Due to Perpetual Hemosiderinuria to Possible Liver Overload Due to Extravascular Hemolysis: Changes in Iron Metabolism in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients On Eculizumab.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4031-4031 ◽  
Author(s):  
Antonio M. Risitano ◽  
Elisa Seneca ◽  
Ludovica Marando ◽  
Massimo Imbriaco ◽  
Ernesto Soscia ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Metabolism ◽  
Renal Cortex ◽  
Transferrin Saturation ◽  
Iron Loss ◽  
Hepatic Iron ◽  
Intravascular Hemolysis ◽  
Hepatic Iron Overload ◽  
Spin Echo Sequence

Abstract Abstract 4031 Poster Board III-967 Iron metabolism in PNH patients is dominated by perpetual iron loss consequent to the chronic complement-mediated intravascular hemolysis; thus, they are prone to develop iron deficiency rather than iron overload, even in presence of large transfusional requirement. Eculizumab (Ecu) has proven effective for the treatment of intravascular hemolysis in PNH patients, resulting in reduction and even abolishment of transfusion requirement and improvement of signs and symptoms of intravascular hemolysis; however, Hb gain is heterogeneous among patients, in most cases due to residual C3-mediated extravascular hemolysis hampering Hb normalization. The goal of our study was to identify possible modifications in iron compartmentalization associated with Ecu treatment and possible clinical consequences. We evaluated iron metabolism in 5 untreated PNH patients and 23 who were receiving Ecu (of whom 4 have been also studied before treatment), combining biochemical parameters with a semiquantitative T2* MRI technology. MRI was performed using four gradient-echo sequences and one spin-echo sequence; signal intensity (SI) was measured on images obtained with each sequence by means of three regions of interest placed in the renal cortex, liver, spleen and at the level of the para-spinal muscle, resulting in a semiquantitative SI value (Grandon et al., Radiology 1994). Within the total patient cohort (regardless they were or were not on Ecu), there was a significant correlation between liver SI and serum ferritin (P<0.001), while kidney SI correlated with the presence of hemosiderinuria (HS, P<0.001). All untreated PNH patients showed similar MRI findings, with significant renal cortex siderosis and normal SI in liver and spleen. This was consistent with overt intravascular hemolysis, as confirmed by biochemical routine testing, and consequent perpetual hemosiderinuria; as expected, all these patients had abundant HS. In contrast, the 23 PNH patients on Ecu showed a distinct and heterogeneous pattern. All patients showed a normal renal SI, with the exception of 2 cases who have recently started Ecu and 2 experiencing Ecu breakthrough; these 4 patients had normal hepatic and splenic SI. All of them (but none of those with normal renal SI) had persistent HS, while only the latter 2 had increased LDH; we conclude that these 4 patients have had residual intravascular hemolysis, and that HS was more sensitive than LDH to identify recent history of intravascular hemolysis. In contrast, the majority of patients showed increased hepatic SI: we found 6 cases with moderate and 5 cases with severe iron overload; in some patients, high hepatic SI was associated with increased SI in the spleen. The 4 patients evaluated before and during treatment showed pre-treatment renal siderosis which progressively disappeared after months of Ecu therapy; in 2 of them, who had a longer exposition to Ecu, moderate hepatic iron overload was demonstrated. Hepatic SI significantly correlated with serum ferritin (P<0.05), but not with transferrin saturation nor with LDH. Iron overload was predictable as a result of persistent transfusional need only in two patients with partial response to Ecu; however, within the whole cohort, patients with suboptimal hematological response (i.e., those with persistent Hb<11) were more likely to develop severe hepatic iron overload (P=0.02). Thus, we hypothesized that iron overload in these patients may be pathophysiilogically linked to persistent extravascular hemolysis; we found a direct correlation between liver SI and both % of C3+ PNH RBCs (P=0.02) and absolute reticulocyte count (P=0.02), which were considered markers of extravascular hemolysis (Risitano et al, Blood 2009). In conclusion, we show by T2* RMI that untreated PNH patients have significant renal siderosis, which tends to disappear during Ecu treatment as a result of the blockade of intravascular hemolysis. However, such blockade of urinary iron loss may render PNH patients susceptible to liver iron overload resulting from transfusions, as well as from residual extravascular hemolysis. While is still not clear the proportion of patients developing clinically significant iron overload requiring specific treatment, we provide evidence that iron metabolism substantially changes during eculizumab treatment, and C3-mediated extravascular hemolysis may play a major role in this process. Disclosures: Risitano: Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Highly Transfused MDS Patients Often Have Cardiac Iron Overload, as Shown by MRI Assessment

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2906-2906
Author(s):  
Laurent Pascal ◽  
Odile Beyne Rauzy ◽  
Sabine Brechignac ◽  
Dominique Vassilieff ◽  
Olivier Ernst ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Cardiac Failure ◽  
Cardiac Disease ◽  
Cardiac Mri ◽  
Iron Content ◽  
Cardiac Iron ◽  
Cardiac Symptoms ◽  
Cardiac Iron Overload ◽  
The Impact

Abstract Abstract 2906 Background: Cardiac complications of transfusional iron overload are well documented in various inherited anemias. In regularly transfused MDS, the deleterious role of iron overload on cardiac disease is more disputed, due in particular to frequent concomitant causes of cardiac failure. Cardiac MRI T2* allows accurate and specific measurement of iron content. Methods: We prospectively evaluated in 4 centers of the GFM by standardized and transferable MRI methods both cardiac T2* according to Anderson (Eur Heart J. 2001Dec;22(23):2171-9) and liver iron content (LIC) according to Gandon (Lancet. 2004 Jan 31;363(9406):357-62), as well as cardiac function by routine echocardiography or MRI in regularly transfused MDS patients. Results: From Dec 2005 to March 2010, 73 patients (pts) were included (14 of them had more than one MRI evaluation over time): 38 M/35F, Median age 68 (24-86); WHO : RA=5, RARS=33, RMCD-RS=3, RMCD=1, RAEB1=9, RAEB2=5, RAEB-T/AML=1, 5q- syndrome=8 and unclassified=8; Karyotype: fav n=50, Int n=9, unfav n=4, failure n=10; IPSS: low n=29, Int-1 n=28, Int-2 n=5 and High n=1, unknown n=10. Median interval from MDS diagnosis and MRI T2* assessment was 49 months (range 0–324). Median serum ferritin at MRI assessment was 1750 ng/ml (range 282–7339) and 54/73 pts were on chelation therapy (CT) (median duration of CT prior to first MRI: 18 months, range 1–125). 37/73 pts had cardiac symptoms and 28 were on cardiac therapy. At first MRI T2* analysis, the median number of RBC units transfused was 68 (range 5–574). Median LIC was 330 micromoles/g/dw (range 40–908). Median Cardiac T2* was 27 ms (range 6–74). 14/73 pts had cardiac iron overload defined by MRI T2* ≤20 ms (19%) and among them 3/73 (4%) had severe cardiac iron overload (T2*≤ 10 ms). LVEF was below normal (55%) in 13/59 cases evaluated. A correlation was found between cardiac T2*and the number of RBC units transfused (Pearson correlation =-0.342, p=0.004) but not with LIC (p= 0.65) and serum ferritin (p=0.21). Cardiac overload was seen in 1/19 (5.5%) pts transfused <50 RBC units, 4/37(12.1%) pts transfused 50–150 units, 9/17 (52.9%) pts transfused >150 units (p= 0.0005). Those 3 pt subgroups also differed in median LIC (μmoles/g/dw) (<50 units= 250, 50–150 units=340, > 150 units=414) (p=0.044 Kruskall-Wallis' test), but not significantly in serum ferritin (p= 0.085). No significant correlation was found between decreased LVEF (< 55%) and cardiac T2* <20 ms (p=0.5), or T2*≤10 ms (p=0.23). In particular, 5/13 pts (38%) with LVEF <55% had T2*<20ms, vs versus 8/46 pts (17%) with LVEF >55% (p= 0.13). However, 1/14, 0/30 and 3/12 pts having received <50, 50–150 and > 150 RBC units had severe cardiac failure (ie LVEF≤35%)(p=0.012). 3/4 pts with severe cardiac failure had T2*< 20ms,compared to 8/54 pts without severe cardiac failure (p=0.023). 14 pts had another cardiac MRI 6 to 34 months (median 18) after the first. All were on CT and had received a median of 60 and 214 PRBC units at first and last MRI, resp. Median Cardiac T2* was 21.6 ms (range 8.5–35.3) and. 28 ms (range 6.4–41) at last and at first assessment, respectively (p=0.3) Conclusions: Moderate and severe post transfusional cardiac iron overload was seen in 19% and 4% of regularly transfused MDS, respectively. The level of cardiac iron overload was well correlated to the number of RBC transfused. The impact of cardiac overload on LVEF was unclear except in pts with severe cardiac impairment (LVEF <35%), possibly suggesting that iron overload is only one of the factors responsible for cardiac disease in many of those elderly patients. Disclosures: No relevant conflicts of interest to declare.

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