Longitudinal analysis of heart and liver iron in thalassemia major

Abstract High hepatic iron concentration (HIC) is associated with cardiac iron overload. However, simultaneous measurements of heart and liver iron often demonstrate no significant linear association. We postulated that slower rates of cardiac iron accumulation and clearance could reconcile these differences. To test this hypothesis, we examined the longitudinal evolution of cardiac and liver iron in 38 thalassemia major patients, using previously validated magnetic resonance imaging (MRI) techniques. On cross-sectional evaluation, cardiac iron was uncorrelated with liver iron, similar to previous studies. However, relative changes in heart and liver iron were compared with one another using a metric representing the temporal delay between them. Cardiac iron significantly lagged liver iron changes in almost half of the patients, implying a functional but delayed association. The degree of time lag correlated with initial HIC (r = 0.47, P < .003) and initial cardiac R2* (r = 0.57, P < .001), but not with patient age. Thus, longitudinal analysis confirms a lag in the loading and unloading of cardiac iron with respect to liver iron, and partially explains the weak cross-sectional association between these parameters. These data reconcile several prior studies and provide both mechanical and clinical insight into cardiac iron accumulation.

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Efficacy of deferasirox in reducing and preventing cardiac iron overload in β-thalassemia

Blood ◽

10.1182/blood-2009-04-217455 ◽

2010 ◽

Vol 115 (12) ◽

pp. 2364-2371 ◽

Cited By ~ 119

Author(s):

Dudley J. Pennell ◽

John B. Porter ◽

Maria Domenica Cappellini ◽

Amal El-Beshlawy ◽

Lee Lee Chan ◽

...

Keyword(s):

Iron Overload ◽

Iron Reduction ◽

Geometric Mean ◽

Iron Concentration ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Liver Iron ◽

Ventricular Ejection Fraction ◽

Cardiac Iron ◽

Cardiac Iron Overload

Cardiac iron overload causes most deaths in β-thalassemia major. The efficacy of deferasirox in reducing or preventing cardiac iron overload was assessed in 192 patients with β-thalassemia in a 1-year prospective, multicenter study. The cardiac iron reduction arm (n = 114) included patients with magnetic resonance myocardial T2* from 5 to 20 ms (indicating cardiac siderosis), left ventricular ejection fraction (LVEF) of 56% or more, serum ferritin more than 2500 ng/mL, liver iron concentration more than 10 mg Fe/g dry weight, and more than 50 transfused blood units. The prevention arm (n = 78) included otherwise eligible patients whose myocardial T2* was 20 ms or more. The primary end point was the change in myocardial T2* at 1 year. In the cardiac iron reduction arm, the mean deferasirox dose was 32.6 mg/kg per day. Myocardial T2* (geometric mean ± coefficient of variation) improved from a baseline of 11.2 ms (± 40.5%) to 12.9 ms (± 49.5%) (+16%; P < .001). LVEF (mean ± SD) was unchanged: 67.4 (± 5.7%) to 67.0 (± 6.0%) (−0.3%; P = .53). In the prevention arm, baseline myocardial T2* was unchanged from baseline of 32.0 ms (± 25.6%) to 32.5 ms (± 25.1%) (+2%; P = .57) and LVEF increased from baseline 67.7 (± 4.7%) to 69.6 (± 4.5%) (+1.8%; P < .001). This prospective study shows that deferasirox is effective in removing and preventing myocardial iron accumulation. This study is registered at http://clinicaltrials.gov as NCT00171821.

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

Blood ◽

10.1182/blood.v112.11.5415.5415 ◽

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*<20ms), being severe in 31,2%. Assessment of liver iron concentration (LIC) showed 95,7% with liver iron overload (>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<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.

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Association of Liver Iron Concentration Levels with Myocardial T2* Responses in Transfusion-Dependent Thalassemia Major Patients Treated with Deferasirox and Deferoxamine- Extension of Cordelia Study

Blood ◽

10.1182/blood.v126.23.2155.2155 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2155-2155 ◽

Cited By ~ 1

Author(s):

Dudley J Pennell ◽

John B Porter ◽

Antonio Piga ◽

Jackie Han ◽

Alexander Vorog ◽

...

Keyword(s):

Research Funding ◽

Iron Concentration ◽

Thalassemia Major ◽

Iron Removal ◽

Liver Iron Concentration ◽

Liver Iron ◽

Time Points ◽

Cardiac Iron ◽

Time Point

Abstract Background: Beta thalassemia major patients (pts) are at an increased risk of heart failure, due to the deposition of iron in the heart causing myocardial siderosis. Intensive long-term iron chelation therapy (ICT) is required to obtain a normal myocardial T2* (mT2* >20 ms). Previously published studies suggested that cardiac iron removal lags changes in liver iron, and liver iron concentration (LIC) may affect the rate of removal of cardiac iron (Porter et al, ASH 2013). The objective of these analyses was to evaluate the association of the severity of LIC levels with the change in mT2* responses in pts with myocardial siderosis when treated with deferasirox (DFX) and deferoxamine (DFO) for up to 24 months (mo) in the CORDELIA study. Due to the very low pt numbers in the DFO arm, the results for these pts are not presented here. Methods: The study design, inclusion, and exclusion criteria have been reported previously (Pennell et al, Am J Hematol. 2015). Pts were categorized into LIC <7, 7 to <15 and ≥15 mg Fe/g dry weight (here after mg/g) both at baseline (BL) and specific visits, to assess the relation of absolute LIC and changes in LIC overtime, with mT2* and cardiac iron concentration (CIC), respectively. During the study, mT2* (ms), and LIC (mg/g) were measured every 6 mo at the same time point. CIC (mg/g) was analyzed as a post hoc parameter derived from mT2*. The change in mT2* was assessed as geometric mean (Gmean)±coefficient of variation (CV), ratio of the Gmean at specific time points divided by that at BL (Gmean at specific time point/Gmean BL) and both CIC and LIC as mean±SD, unless otherwise specified. Results: Of 197 pts, 160 (81.2%) completed 12 mo of treatment and 146 (74.1%) entered into the extension study whereas 103 pts continued on initially assigned treatment. Pts completing 24 mo of treatment included 65 (87.8%) of 74 pts (mean age 20.1±6.9 years, 59.5% male) on DFX and the results for these pts are presented as follows. Average actual doses (mg/kg/d) were 26.7±8.9, 31.5±7.4, 38.0±2.9 for LIC <7, 7 to <15, ≥15, respectively, during the extension study. The LIC levels for pts categorized by LIC <7, 7 to <15 and ≥15 improved from BL to Mo 24 as follows: 72% decrease (mean absolute change, -15.1±14.1), 66% decrease (-26.6±13.0), and 19% decrease (-10.2±15.7), respectively. For pts with BL LIC <7, 7 to <15, ≥15, mT2* improved from BL to Mo 24 as follows: 43% increase (14.0±18.1 to 21.6±31.1; mean abs change, 7.8±4.0), 50% increase (12.3±34.4 to 19.1±46.4; 8.0±6.0), and 30% increase (11.1±30.8 to 14.5±40.8; 4.1±5.0). The CIC values improved from BL to Mo 24 by 38% (1.8±0.4 to 1.1±0.5), 40% (2.3±0.9 to 1.4±0.7), and 23% (2.6±1.0 to 1.9±1.0), respectively. The mT2* responses for pts categorized according to visit specific LIC levels (LIC <7, 7 to <15, ≥15) from BL to Mo 12 were 22% increase (mean abs change, 3.7±4.3) in LIC <7, 21% increase (2.7±2.0) in LIC 7 to <15, and 7% increase (1.5±3.2) in LIC ≥15. From BL to Mo 24, mT2* increased by 51% (mean abs change, 7.8±5.3), 35% (4.1±2.5), and 11% (2.0±4.4), respectively. The CIC levels improved from BL to Mo 24 by 40% (mean abs change, -1.0±0.8) in LIC <7, 31% (-1.0±0.6) in LIC 7 to <15, and 6% (-0.1±0.8) in LIC ≥15. The change in mT2* (Gmean ratio) at Mo 6, 12, 18 and 24 are shown in the Figure A. The mT2* response was higher in pts who achieved a lower LIC category (LIC <7) at respective time points and this change in mT2* was more apparent at 18 and 24 mo of treatment with DFX. Discussion: Overall, DFX treatment resulted in a substantial decrease in LIC and improved mT2*. These results suggest a greater difference in mT2* improvement and CIC reduction in pts who achieved lower LIC during treatment with DFX. This divergence was progressive with time, being maximal at Mo 24. Thus, a therapeutic response in LIC with DFX may be associated with a greater likelihood of improving mT2*. Pts with high LIC ≥15 may require an effective long-term treatment with higher doses of ICT to have an improvement in mT2*, suggesting that cardiac iron removal is likely to be slow in heavily iron overloaded pts. These results are consistent with the previous report which showed a significant decrease in LIC and increased mT2* responses at Mo 36 in pts who attained lower end-of-year LIC levels when treated with DFX (Porter et al, ASH 2013) and highlight the potential value of monitoring the liver and cardiac responses during ICT. To further understand the kinetics between liver and cardiac iron removal, prospective investigation is warranted. Disclosures Pennell: Novartis: Consultancy, Research Funding; Apotex: Consultancy, Research Funding. Porter:Celgene: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria. Piga:Acceleron: Research Funding; Cerus: Research Funding; Apopharma: Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding; Celgene Corporation: Honoraria. Han:Novartis: Employment. Vorog:Novartis: Employment. Aydinok:Cerus: Research Funding; Sideris: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Stratification for Age in Transfusion-Dependent Thalassemia

Blood ◽

10.1182/blood-2018-99-112042 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3638-3638

Author(s):

Alessia Pepe ◽

Laura Pistoia ◽

Mario Rocca ◽

Giovanni Palazzi ◽

Francesco Sorrentino ◽

...

Keyword(s):

Iron Overload ◽

Iron Concentration ◽

Cardiac Complications ◽

Liver Iron ◽

Number Of Patients ◽

Cardiac Iron Overload ◽

Group 2 ◽

Magnetic Resonance Imaging Mri ◽

Group 1

Abstract Introduction. Transfusion-dependent β-thalassemia (TDT) is the most severe clinical form of β-thalassemia and requires regular long-term red cell transfusions for survival. This study aimed to examine the association of age with the presence of iron overload assessed by Magnetic Resonance Imaging (MRI) and cardiovascular and endocrine complications in TDT patients. Methods. We considered all TDT patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project at the first MRI examination. Iron concentrations were measured by T2* multiecho technique. All complications were classified according to international guidelines. Results. Three groups of patients were identified: age<12 years (group 0, N=53), age between 12-17 years (group 1, N=100) and age≥18 years (group 2, N=1857). The number of transfusional units in the 12 months before the MRI scan resulted significantly lower in group 0 versus both group 1 (20.8±5.3 vs 34.8±10.6; P<0.0001) and group 2 (20.8±5.3 vs 39.2±10.9; P>0.0001) and in group 1 versus group 2 (P=0.021). The Table shows the comparison of clinical characteristics among the 3 groups. Serum ferritin levels were significantly higher in both groups 0 and 1 when compared to group 2. Liver aminotransferases were significantly lower in group 1 than in group 2. The number of patients with MRI LIC (liver iron concentration) >3 mg/g dw was significantly higher in group 1 than in group 2 and the number of patients with global heart T2*<20 ms was significantly lower in group 0 than in group 2. Among the endocrinopathies, hypogonadism, hypothyroidism and osteoporosis were significantly less frequent in groups 0 and 1 than in group 2 while diabetes was significantly less frequent only in group 1 when compared to group 2. Frequency of heart failure was comparable among the groups while the frequency of arrhythmias was significantly lower in group 1 than in group 2. The types of chelation regimens were significantly different among groups (<0.0001) (see Figure). Conclusions. Younger patients had more hepatic iron, despite the significant lower transfusional burden. Cardiac iron overload occurs early in TDT patients but it is more frequent in older patients. Endocrinopathies (excluding diabetes) and cardiac complications become clinically evident during the second decade and are time-dependent processes. Our data suggest the need for an effective strategy to prevent iron overload since early childhood, in order to reduce its toxic effect and prevent the development of long-term complications. Figure. Figure. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

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Optimizing Iron Chelator Treatment in Cardiac and Hepatic Siderosis: Efficacy of Divided Deferasirox (EXJADER) – Doses

Blood ◽

10.1182/blood.v118.21.2110.2110 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2110-2110

Author(s):

Regine Grosse ◽

Andrea Jarisch ◽

Jin Yamamura ◽

Peter Nielsen ◽

Roland Fischer ◽

...

Keyword(s):

Iron Overload ◽

Treatment Period ◽

Iron Concentration ◽

Iron Chelator ◽

Liver Iron ◽

Once Daily ◽

Cardiac Iron ◽

Cardiac Siderosis ◽

Cardiac Iron Overload ◽

The Mean

Abstract Abstract 2110 Introduction: Iron chelation is the life-saving therapy in patients with chronic transfusion therapy. Treatment with deferoxamine, deferiprone or deferasirox has dramatically improved the life expectancy, but still myocardial siderosis and hepatic siderosis is cause of morbidity and mortality in regularly transfused patients with ß-thalassemia major (TM) or Diamond-Blackfan Anemia (DBA). Deferasirox (DSX) a once-daily oral iron chelator has demonstrated efficacy in reducing hepatic iron and body iron burden, as well as cardiac iron. But in patients with severe cardiac siderosis (T2* ≤ 10ms) a combination therapy with deferiprone (Ferriprox®) and deferoxamine (Desferal®) is the recommended therapy. However, some patients will not benefit from this treatment due to unacceptable toxicity, poor response or noncompliance. Method: We tested a twice-daily deferasirox (Exjade®) -dose with special respect to its efficacy on reducing cardiac iron overload. A group of six patients with severe secondary siderosis was studied, TM (n=5) and DBA (n=1), (5 females, age 8–37 years, mean age 27.7 years). In all patients the liver iron concentration was measured repeatedly by SQUID biosusceptometry or by magnetic resonance imaging (MRI) using the MRI-R2 technique (St. Pierre et al, 2005). In 4 patients with severe cardiac siderosis (T2* ≤ 10ms) we also followed the cardiac iron concentration by MRI using a single breath-hold, multi-echo T2* method. Patients received a daily DSX dose of 19 mg/kg/d – 45 mg/kg/d, with a mean dose of 32 mg/kg/d. Results: The mean initial liver iron concentration of 2.7 mg/g-liver (0.96 – 5.5mg/g) decreased to 1.5 mg/g-liver (0.6 – 3.9 mg/g). The mean monthly liver iron clearance was 6.8%/month (1.7 – 16.8%/month) in a treatment interval of 4 – 26 months (mean: 9.8 months), the patients demonstrated a significant liver iron reduction of 44.4%. The mean serum ferritin was reduced from 3048 μg/l to 1786 μg/l. The mean monthly cardiac iron clearance was 3.1%/month (1.2 – 4.7%/month) and the mean T2* value improved from 9.5 ms to 14.3 ms (+50%). We showed a substantial improvement in patients with severe cardiac siderosis with a T2* improvement of 50 % after a mean treatment period of 12 months with a mean DSX dose of 32 mg/kg/d. In comparison, an improvement of 23.8% was found in 6 patients with T2* < 10 ms, after a treatment period of 18 months with a once daily DSX mean dose of 38 mg/kg/d (Pathare et al, 2010). Other authors reported an improvement of 10.8% in 47 patients (T2* < 10 ms, treatment period 12 months) with a once daily DSX mean dose of 32 mg/kg/d (Pennell et al, 2009). No severe side effects were seen in our patients and only minor increases in creatinine values, which were reversible with dose reduction. Conclusion: Deferasirox divided in twice daily doses is a safe and effective therapy for patients with severe cardiac iron overload (T2* < 10ms) or hepatic iron overload, who do not well tolerate a combination therapy with deferiprone and deferoxamine. Disclosures: Off Label Use: Deferasirox (Exade)is given instead of a once daily dose, in a twice daily divided dose. The daily dose of Deferasirox is in recommended range.

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Association Between Cardiac Iron Clereance and Hepatic Siderosis

Blood ◽

10.1182/blood.v128.22.4833.4833 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4833-4833

Author(s):

Alessia Pepe ◽

Laura Pistoia ◽

Domenico D'Ascola ◽

Maria Rita Gamberini ◽

Francesco Gagliardotto ◽

...

Keyword(s):

Iron Overload ◽

Iron Concentration ◽

Thalassemia Major ◽

Hepatic Iron ◽

Liver Iron Concentration ◽

Liver Iron ◽

Cardiac Iron ◽

Follow Up Study ◽

Hepatic Iron Overload

Abstract Introduction. The aim of this multicenter study was to evaluate in thalassemia major (TM) if the cardiac efficacy of the three iron chelators in monotherapy was influenced by hepatic iron levels over a follow up of 18 months. Methods. Among the 2551 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we evaluated prospectively the 98 patients those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans and who showed evidence of significant cardiac iron (global heart T2*<20 ms) at the basal MRI. Iron overload (IO) was measured by T2* multiecho technique. We used cardiac R2* (equal to 1000/T2*) because cardiac R2* is linearly proportional to cardiac iron and hepatic T2* values were converted into liver iron concentration (LIC) values. Results. We identified 3 groups of patients: 47 treated with deferasirox (DFX), 11 treated with deferiprone (DFP) and 40 treated with desferrioxamine (DFO). Percentage changes in cardiac R2* values correlated with changes in LIC in both DFX (R=0.469; P=0.001) and DFP (R=0.775; P=0.007) groups. All patients in these 2 groups who lowered their LIC by more than 50% improved their cardiac iron (see Figure 1). Percentage changes in cardiac R2* were linearly associated to the log of final LIC values in both DFX (R=0.437; P=0.002) and DFP groups (R=0.909; P<0.0001). Percentage changes in cardiac R2* were not predicted by initial cardiac R2* and LIC values. In each chelation group patients were divided in subgroups according to the severity of baseline hepatic iron overload (no, mild, moderate, and severe IO). The changes in cardiac R2* were comparable among subgroups (P=NS) (Figure 2). Conclusion. In patients treated with DFX and DFP percentage changes in cardiac R2* over 18 months were associated with final LIC and percentage LIC changes. In each chelation group percentage changes in cardiac R2* were no influenced by initial LIC or initial cardiac R2*. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc..

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Association between serum ferritin and liver iron concentration with cardiac iron in pediatric thalassemia major patients

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/1532-429x-18-s1-p295 ◽

2016 ◽

Vol 18 (S1) ◽

Cited By ~ 1

Author(s):

Antonella Meloni ◽

Maddalena Casale ◽

Aldo Filosa ◽

Maria Giovanna Neri ◽

Lorella Pitrolo ◽

...

Keyword(s):

Serum Ferritin ◽

Iron Concentration ◽

Thalassemia Major ◽

Liver Iron Concentration ◽

Liver Iron ◽

Cardiac Iron

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Mobilization of Auto-Stem Cells in the Thalassemia Major and Relationship with Iron Overload

Blood ◽

10.1182/blood-2020-141775 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 7-7

Author(s):

Xiaoqin Feng ◽

Yuelin He ◽

Bindanda Mvuama Van Timothee ◽

Jing Du ◽

Chunfu Li ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Iron Overload ◽

Thalassemia Major ◽

Severe Liver ◽

Liver Iron ◽

Cardiac Iron ◽

Significant Difference ◽

Cardiac Iron Overload ◽

Liver Iron Overload

Objectives: The hematopoietic stem cells transplantation (HSCT) is the only curable treatment in current for thalassemia major (TM).The quantity of auto stem cell of TM patients are very important for rescue the patients in case of failure of HSCT, and auto stem cells of TM will be used as target cells for gene therapy (GT) in the near future. Iron overload (IOL) can damage the hematopoiesis of TM. How to collect the auto stem cells in TM patients? How about the affects of iron overload in the mobilization and collection of auto stem cell? The aim of this study was to analyze quantity of auto stem cells in the TM and the affects of iron overload (IOL). Methods: We retrospectively analyzed a total of 134 patients and 25 normal donors undergoing PBSCs collection between January 2012 and December 2019. Patients with serum ferritin levels over 1,000 ng/mL and with a history of red blood cell transfusions prior to stem cell collection were defined as a group having transfusion-associated iron overload (IOL). In total one hundred and thirty-four patients and twenty-five donors were subcutaneous administrated G-CSF (Granulocyte Colony Stimulating Factor) 10 mg/kg/d Injection for 5 days, PBSCs was collected using a large volume leukapheresis (LVL) procedure. The data of WBC, MNC and CD34+ in product were analyzed by SPSS 20 software. Results: In 134 patients, median age is 8.60 range: (1-17),and 25 Normal donors, median age is 7.5 range: (1-18). The results demonstrated that cells either in patients with thalassemia or normal donors were effectively mobilized by G-CSF (10 mg / kg/d),as these children showed a marked increase in white blood cells and MNC cells in peripheral blood, reaching a peak in 4 to 5 days after the injection of G- CSF alone. Comparison of the MNC [(6.7±3.5) ×10⁸/kg vs (7.2±4.77) ×10⁸/kg] and CD34+cells [(10.29±4.5)×10⁶/kg vs (10.9±6.8)×10⁶/kg] in collected product in TM patients and normal donors groups revealed no significant difference. There was no significant difference between different Ferritin level (Mild, Intermediate and Severe) on WBC, MNC, and CD34+ in each group at the time point studied. But there was significant difference on MNC number (Normal liver iron (7.73±2.69)×10⁸/kg, Mild liver iron overload (7.66±4.64)×10⁸/kg, Intermediate (6.18± 2.84) ×10⁸/kg compared to Severe liver iron (4.45±3.34)×10⁸/kg, P=0.039. Significant difference was also can be seen in number of MNC of product in patients with intermediate cardiac iron overload compared to normal cardiac iron overload and mild cardiac iron overload (2.76±0.97) ×10⁶/kg vs(6.86±3.39) ×10⁶/kg and (6.88±3.72)×10⁶/kg, P=0.030. There was a statistically significant difference positive correlation between median age (P=0.011) and MNC/Kg (P=0.030). Conclusion:The quantity of mobilization of PBSC in TM patients had no significant difference compare to normal donor. The MNC in product was statistically decreased in intermediate cardiac iron overload and severe liver iron overload (IOL) subgroup. It indicated that iron overload (IOL) in organs may negatively relate to proliferation and mobilization of stem cells in TM. Further quality study of PBSC such as stem cell culture and ability of proliferation should be more evaluated. The sufficient quantity and high quality auto stem cell from TM patient can be more used in the future. Disclosures No relevant conflicts of interest to declare.

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MRI Evaluation of Liver and Cardiac Iron Overload Impact on Hematopoietic Stem Cell Transplantation with β-Thalassemia Major

Blood ◽

10.1182/blood-2019-128903 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5738-5738

Author(s):

Libai Chen ◽

Yuelin He ◽

Jianyun Wen ◽

Wenjing Yang ◽

Xuan Liu ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Iron Overload ◽

Hematopoietic Stem Cell ◽

Serum Ferritin ◽

Iron Concentration ◽

Thalassemia Major ◽

Liver Iron ◽

Hematopoietic Stem ◽

Cardiac Iron

OBJECTIVE: To assess the effects of liver and cardiac iron overload detected by magnetic resonance imaging (MRI) T2* on hematopoietic stem cell transplantation in children with β-thalassemia major. METHODS:Summary of 380 cases of β-thalassemia major patients more than 5 years old in Nanfang hospital, southern medical university from 2012 to 2019.Iron concentrations in the liver and heart were calculated based on MRI T2* test results of liver and heart. Age, serum ferritin, left ventricular ejection fraction (LVEF), and liver function were compared to evaluate the effect of iron overload on organ function in patients with β-thalassemia major before transplantation.168 patients underwent allogeneic hematopoietic stem cell transplantation, 48 were HLA-mismatched transplantation, and 120 were HLA-identical allogeneic hematopoietic stem cell transplantation.To analysis the influence between implantation rate, hematopoietic reconstruction time, mortality, and common complications after transplantation such as graft-versus-host disease, hepatic venous obstruction, infection, immune hemolysis, and pancytopenia and liver and cardiac iron overload detected by magnetic resonance imaging (MRI) T2*. RESULTS:Myocardial iron overload occurred in 73 cases (19.2%), including 29 cases of cardiac T2*15~20 ms (mild), 23 cases of 10~14 ms (moderate), and 21 cases of <10 ms (severe).There were 305 cases (80.2%) with liver iron overload, including 98 cases with 2.7~6.3 ms (mild), 166 cases with 1.4~2.7 ms (moderate), and 41 cases with <1.4 ms (severe).LVEF decreased in 5 cases (1.6%).Liver iron was positively correlated with serum ferritin (r=0.523, P=0.001), cardiac iron concentration was positively correlated with serum ferritin (r=0.33, P=0.1), age was positively correlated with cardiac iron concentration (r=0.4, P=0.14), and age was negatively correlated with left ventricular ejection fraction (r=-0.36, P=0.001).After transplantation, liver iron concentration was positively correlated with hemoglobin implantation time (r=0.49, P=0.043), heart iron concentration was positively correlated with mortality (r=0.39, P=0.012), serum ferritin was negatively correlated with implantation rate (r=-0.26, P=0.012), and serum ferritin was positively correlated with infection incidence correlation (r=0.441, P=0.034).There were no statistically significant differences in liver, heart MRI T2*, liver iron concentration and heart iron concentration between the two groups before and after transplantation. CONCLUSION:Magnetic resonance imaging (T2*) is an effective and non-invasive method to detect the iron overload in the heart and liver caused by blood transfusion in β-thalassemia patients. Iron overload can have adverse effects on hematopoietic stem cell transplantation,and effective iron removal before transplantation can improve the success rate of transplantation.Quantitative assessment of iron overload in the liver and heart by MRI can be used as a necessary examination before transplantation. Disclosures No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood.v124.21.4900.4900 ◽

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.

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