Do We Need the Chelation Therapy during Intensive Treatment of Acute Lymphoblastic Leukemia (ALL) in Children?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4881-4881
Author(s):  
Michal Romiszewski ◽  
Michal Matysiak ◽  
Katarzyna Pawelec
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
The Body ◽  
Intensive Treatment ◽  
Intensive Chemotherapy ◽  
Hematopoietic Stem ◽  
Ferritin Concentration ◽  
Serum Ferritin Concentration ◽  
The Mean

Abstract Introduction Children with ALL during the intensive chemotherapy receive multiple transfusions of packed red blood cell (pRBC) that may lead to iron overload. With each transfusion of pRBC the body is supplied with an about 200-250 mg of iron, which excessive accumulation in tissues, due to the lack of mechanism for its active excretion, may cause toxic organ damage. Methods The aim of the study was to evaluate the serum ferritin concentration in children with ALL, depending on the amount of transfused pRBCs and to determine the group of patients with a risk of iron overload. The study patients included 54 children with newly diagnosed ALL treated at the Department of Pediatrics, Hematology and Oncology between 2008 and 2011, according to the ALL IC BFM 2002 therapy protocol. Prior to initiation the treatment and during the intensive chemotherapy, serum ferritin concentration and the number of pRBC transfusions (ml/kg) were assessed separately for each of the three ALL risk groups-standard risk (SR), intermediate risk (IR) and high risk (HR). Results After the intensive chemotherapy the mean ± standard deviation (SD) of serum ferritin concentration in group HR (2770 ± 1175 ng/ml) was significantly higher compared to the median in group SR 844.4 ng/ml (452.5; 1316) (p = 0.0007) and the mean ± SD in group IR-1270 ± 673.1 ng/ml (p = 0.0040). Throughout the intensive chemotherapy children in HR group received the largest volume of pRBC transfusions (ml/kg) (156.2 ± 68.31 ml/kg). In IR and SR groups the amounts of transfused pRBCs were comparable, respectively 113.5 ± 39.86 and 113.8 ± 29.56 ml/kg. Significant positive correlation was found between the serum ferritin concentration and the total amount of transfused pRBCs (ml/kg) after intensive chemotherapy (p <0.0001). After intensive treatment the concentration of serum ferritin exceeding 1000 ng/ml, that has traditionally been used as a trigger for chelation therapy, was found in 30 of 54 patients, for a prevalence in the entire cohort of 55,6% including 6 out of 6 patients in HR group (100%), 14 out of 22 patients in IR group (63,6%) and 10 out of 24 patients in SR group (41,7%). The group of patients with post-treatment serum ferritin concentration exceeding 1000 ng/mL, received significantly more pRBC transfusions (ml/kg) (139.8 ± 44.92) than the groups with serum ferritin levels between 500-1000 ng/mL (103.6 ± 18.96) (p <0.001) and <500 ng/mL-83.52 ± 17.66 (p <0.05). Conclusions These observations indicate a need of monitoring the cumulative volumes of pRBC transfusions, especially in children with ALL HR group. There is a need of routine screening for iron overload using serum ferritin in patients during intensive chemotherapy, in order to identify patients with indications for early iron chelation therapy. This is particularly important because some of them will be candidates to a hematopoietic stem cell transplantation, whereas iron overload adversely affects outcome of transplantation. Disclosures No relevant conflicts of interest to declare.

scholarly journals T2*-magnetic resonance relaxometry of the liver in the quantitative assessment of iron overload

2018 ◽  
Vol 20 (2) ◽  
pp. 55-58
Author(s):  
A M Titova ◽  
G E Trufanov ◽  
V A Fokin
Keyword(s):  
Magnetic Resonance ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Quantitative Assessment ◽  
Accurate Estimate ◽  
The Body ◽  
Ferritin Concentration ◽  
Neoplastic Processes ◽  
Serum Ferritin Concentration ◽  
Reliable Marker

For objective quantitative assessment of iron overload in 60 patients with hemochromatosis of different genesis, T2*-magnetic resonance relaxometry of the liver was performed. The results of the latter were compared with the concentration of serum ferritin, which is by far the most common marker of iron overload. It has been established that T2*-magnetic-resonance relaxometry is a non-invasive, highly effective method of objective quantitative assessment of iron overload in patients of the hematological profile, in comparison with the serum ferritin concentration, which is not specific, since its change can be influenced by inflammatory and neoplastic processes in The organism, often found in patients with oncohematological profile. Thus, according to T2*-magnetic resonance relaxometry of the liver, all patients were divided into two groups: with iron overload and with no overload, the latter among the total number of subjects was 13,3%. The explanation of the increase in serum ferritin concentration in these patients was the presence of identified inflammatory foci in the body. In most patients (86,6%), iron overload was confirmed by T2*-magnetic resonance relaxometry measurements. However, at each degree of overload, there was no clear regularity in the proportional increase in serum ferritin concentration of the intensity of pathological changes revealed by T2*-magnetic resonance relaxometry. Thus, ferritin cannot remain a reliable marker for iron overload. In general, magnetic resonance T2 *-relaxometry provides the most accurate estimate of the degree of iron overload in the liver. T2*-magnetic resonance relaxometry should be included in the protocol of examination of patients with suspicion of the presence of iron overload.

Extreme hyperferritinaemia; clinical causes

2013 ◽  
Vol 66 (5) ◽  
pp. 438-440 ◽  
Author(s):  
Martin A Crook ◽  
Patrick L C Walker
Keyword(s):  
Liver Disease ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Malignant Disease ◽  
Hepatic Disease ◽  
Blood Transfusions ◽  
Still’S Disease ◽  
Ferritin Concentration ◽  
Serum Ferritin Concentration ◽  
Multiple Blood

There are many causes of raised serum ferritin concentrations including iron overload, inflammation and liver disease to name but a few examples. Cases of extreme hyperferritinaemia (serum ferritin concentration equal to or greater than 10 000 ug/l) are being reported in laboratories but the causes of this are unclear. We conducted an audit study to explore this further. Extreme hyperferritinaemia was rare with only 0.08% of ferritin requests displaying this. The main causes of extreme hyperferritinaemia included multiple blood transfusions, malignant disease, hepatic disease and suspected Still's disease.

scholarly journals Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2741-2748 ◽  
Author(s):  
NF Olivieri ◽  
G Koren ◽  
D Matsui ◽  
PP Liu ◽  
L Blendis ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Concentration ◽  
Transferrin Saturation ◽  
Dramatic Improvement ◽  
Thalassemia Intermedia ◽  
Ferritin Concentration ◽  
Iron Stores ◽  
Tissue Iron ◽  
Serum Ferritin Concentration

Abstract In patients with thalassemia intermedia in whom hyperabsorption of iron may result in serious organ dysfunction, an orally effective iron- chelating drug would have major therapeutic advantages, especially for the many patients with thalassemia intermedia in the Third World. We report reduction in tissue iron stores and normalization of serum ferritin concentration after 9-month therapy with the oral chelator 1,2- dimethyl-3-hydroxypyrid-4-one (L1) in a 29-year-old man with thalassemia intermedia and clinically significant iron overload (SF 2,174 micrograms/L, transferrin saturation 100%; elevated AST and ALT, abnormal cardiac radionuclide angiogram) who was enrolled in the study with L1 75 mg/kg/day after he refused deferoxamine therapy. L1-Induced 24-hour urinary iron excretion during the first 6 months of therapy was (mean +/- SD, range) 53 +/- 30 (11 to 109) mg (0.77 mg/kg), declining during the last 3 months of L1 to 24 +/- 14 (13–40) mg (0.36 mg/kg), as serum ferritin decreased steadily to normal range (present value, 251 micrograms/L). Dramatic improvement in signal intensity of the liver and mild improvement in that of the heart was shown by comparison of T1- weighted spin echo magnetic resonance imaging with images obtained immediately before L1 administration was observed after 9 months of L1 therapy. Hepatic iron concentration decreased from 14.6 mg/g dry weight of liver before L1 therapy to 1.9 mg/g liver after 9 months of therapy. This constitutes the first report of normalization of serum ferritin concentration in parallel with demonstrated reduction in tissue iron stores as a result of treatment with L1. Use of L1 as a therapeutic option in patients with thalassemia intermedia and iron overload appears warranted.

Hepatic computed tomography for monitoring the iron status of haemodialysis patients with haemosiderosis treated with recombinant human erythropoietin

1991 ◽  
Vol 81 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Sergio De Marchi ◽  
Emanuela Cecchin
Keyword(s):  
Computed Tomography ◽  
Serum Ferritin ◽  
Recombinant Human Erythropoietin ◽  
Chelation Therapy ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Ferritin Concentration ◽  
Human Erythropoietin ◽  
Serum Ferritin Concentration ◽  
Erythropoietin Treatment

1. A randomized, partial-crossover study was conducted in uraemic patients with dialysis-associated anaemia and transfusional iron overload to evaluate the effects of desferrioxamine chelation therapy and of recombinant human erythropoietin treatment on hepatic iron storage determined by computed tomography, as well as by serum ferritin concentration and transferrin saturation. 2. Twenty-one haemodialysis patients with moderate iron overload, confirmed by values of serum ferritin concentration, transferrin saturation and hepatic computed tomography density exceeding 1000 μg/l, 45% and 68 Hounsfield units respectively, were randomly allocated to three groups and were followed for 12 months. 3. During the first 6 months group 1 (n = 7) received desferrioxamine chelation therapy (30 mg/kg intravenously three times a week) and group 2 (n = 7) underwent recombinant human erythropoietin treatment (36 units/kg intravenously three times a week). Thereafter, in the second 6 months of observation patients in group 1 were switched to receive recombinant human erythropoietin. Because of a poor response in the desferrioxaminetreated group in the initial 6 months, patients in group 2 continued on the maintenance dose of recombinant human erythropoietin (18 units/kg three times a week) until the end of the trial. Patients in group 3 (n = 7) were maintained on placebo throughout the study. 4. In comparison with placebo, recombinant human erythropoietin treatment, but not desferrioxamine chelation therapy, reduced serum ferritin concentration, transferrin saturation and hepatic computed tomography density, and was associated with a rise in haemoglobin and packed cell volume. Hepatic computed tomography density, serum ferritin concentration and transferrin saturation decreased in 13 out of 14 patients (93%) during treatment with recombinant human erythropoietin. However, when the changes in hepatic computed tomography density were compared with those in the biochemical indices, we observed that the decreases in serum ferritin concentration and transferrin saturation were much slower and delayed. More specifically, within 6 months of starting recombinant human erythropoietin treatment, hepatic computed tomography density was normalized in 13 out of 14 patients (93%), whereas serum ferritin concentration and transferrin saturation were within the normal limits in only two (14%) and six patients (43%), respectively. 5. In conclusion, the strategies for monitoring the iron status of haemodialysis patients with transfusional haemosiderosis may evolve to a new level of sophistication with the introduction of computed tomography scanning. This technique has the advantage of estimating directly the effect of recombinant human erythropoietin treatment on hepatic iron storage. Hepatic computed tomography density is complementary to serum ferritin concentration and transferrin saturation in monitoring the iron status of haemodialysis patients treated with recombinant human erythropoietin.

Iron Chelation Treatment with Oral Solution of Deferiprone in Young Children with Hemoglobinopathies,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3204-3204
Author(s):  
Alexandros Makis ◽  
Nikolaos Chaliasos ◽  
Antigone Siamopoulou
Keyword(s):  
Young Children ◽  
Serum Ferritin ◽  
Iron Chelation ◽  
Oral Solution ◽  
Beta Thalassemia ◽  
Ferritin Concentration ◽  
Safety And Efficacy ◽  
Serum Ferritin Concentration ◽  
Daily Dose ◽  
The Mean

Abstract Abstract 3204 Background - Aim. Children with transfusion dependent hemoglobinopathies rapidly develop iron overload in vital organs and iron removal with chelating agents is required early in life and in some cases after the age of 2. The oral administration of iron chelation is most welcome by thalassemic children and their parents who have problems with the discomfort and side effects of deferoxamine injections. Deferiprone, previously only in tablet form, was not suitable for young children under the age of 5 years. Recently the solution form of deferiprone has been introduced. There are limited clinical data on the safety and efficacy of deferiprone at a very young age. The aim of our study was the presentation of data regarding the safety and efficacy of liquid oral solution of deferiprone in young children with hemoglobinopathies less than 10 years old. Patients and methods. Nine young children (5 boys, 4 girls) receiving oral solution of deferiprone (Ferriprox® 100 mg/mL) were studied. The mean age at the beginning of the treatment was 6.5 (range 2–10). Six children had beta-thalassemia major, 1 thalassemia intermedia and 2 sickle cell/beta thalassemia. The mean number of red blood cell transfusions during the previous year was 10.6 (range 8–15). All the children had chronic iron overload requiring chelation therapy, as defined by serum ferritin concentration [mean ± standard error (SE): 2440±1275 μg/L]. All children were naïve to iron chelation therapy before this study, except for 2 patients who were on deferoxamine (mean dose=35 mg/kg/day; mean duration of use=1.5 years). One child was splenectomized. All children had negative anti-hepatitis C antibody status at baseline. Treatment was initiated at a daily dose of 50 mg/kg, divided into 3 doses, for the first 2 weeks. The dose was increased to 75 mg/kg, for another 2 weeks. If serum ferritin concentration at baseline was greater than 2500 μg/L, the dose was further increased to a total daily dose of 100 mg/kg after 4 weeks therapy. After initiation of the treatment, full blood count was assessed weekly, serum ferritin monthly, and liver and renal function bimonthly. The mean duration of treatment was 9.5 months (range 2–15 months). To evaluate the efficacy and safety of oral deferiprone treatment, biochemical parameters such as serum ferritin and liver enzymes were analyzed using the Student t-test. All parameters are presented as mean± SE. P-values less than 0.05 were considered statistically significant. Results. All children received the oral deferiprone without any problems of compliance. The hematological and biochemical markers during treatment are shown in Table 1. Adverse reactions to deferiprone were mild and transient: abdominal discomfort and diarrhea at initiation of therapy (1 child) and mild neutropenia (1 child) resolved within 8 days with no need of discontinuation of treatment. Deferiprone oral solution was effective in reducing serum ferritin (mean±SD) (initial 2440±1275 μg/L vs final 2030±915 μg/L, p<0.005) (Figure 1). Five children of the study were <6 years old. The baseline serum ferritin of these children was significantly lower than older children (2250 μg/L±880 vs 2950 μg/L±1550, p<0.005). The differences in changes in serum ferritin did not reach statistical significance. Conclusions. This small study shows that oral solution of deferiprone was well tolerated by young children and its use was not associated with major safety concerns. Furthermore, it was effective in decreasing serum ferritin. Further studies with large number of patients and longer follow-up, are needed to confirm the safety and efficacy profile of deferiprone in childhood. Disclosures: No relevant conflicts of interest to declare.

Transfusional Iron Overload In An Adult Sickle Cell Disease Population: Epidemiology, Prevalence, and Management

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1005-1005 ◽  
Author(s):  
James Son ◽  
Hongyan Xu ◽  
Nadine J Barrett ◽  
Leigh G Wells ◽  
Latanya Bowman ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Organ Damage ◽  
Morbidity And Mortality ◽  
Genotype Distribution ◽  
Cell Disease ◽  
The Mean

Abstract Transfusional iron (Fe) overload remains a significant problem among patients with chronic, transfusion dependent anemias, especially in transfusion dependent ß-thalassemia (Thal) syndromes. If not treated vigorously with chelation, Fe overload in Thal is associated with significant organ damage, especially with chronic liver disease and cardiac abnormalities which can contribute to morbidity and mortality. In recent decades, the significance of Fe overload in sickle cell disease (SCD) has also been recognized especially among pediatric patients on chronic transfusion regimens predominantly for primary and secondary prevention of stroke. The prevalence and significance of this problem among adult SCD patients is less clear, although it is widely believed that episodic, mostly unnecessary transfusion practices play a more prominent role in this patient population. There have been reports of an association between iron overload and increased morbidity and mortality among adult SCD patients; it has also been speculated that the chronic inflammatory state that exists in SCD affords some degree of protection against severe organ damage through upregulation of hepcidin and sequestration of Fe in these patients. We performed a retrospective review of 635 adult SCD patients followed at our Center to define and ascertain the epidemiology, prevalence, etiology, and clinical correlates of transfusional Fe overload. Fe overload was defined as two consecutive serum ferritin values of > 1000 ng/ml. 80 patients (12.6%) met this criterion. Of these, 38 were male and 42 were female. Genotype distribution was: 73 SS, 3 S-β+ thal, 2 S-β0 thal and 2 SC. The mean age was 35.9 (range 18-69). Out of the 80 patients with transfusional Fe overload, 24 (30%) were/had been on a chronic transfusion regimen (23 for secondary or primary stroke prevention and one for childhood cardiomyopathy). Seventy percent of the patients (n=56) developed Fe overload from episodic transfusions predominantly performed at outlying community hospitals. The mean highest ferritin value was 4991 ng/ml (range 1,052-16,500). There was no correlation between ferritin levels and the number of hospitalizations or painful episodes (p=0.9). Thirty seven patients (46.2%) had a history of chelation therapy (with desferoxamine, deferasirox, or both). In 25 patients who have been on deferasirox for a period of 6 months or more, serum ferritin levels decreased from 4452.3 to 3876.6 ng/ml (p=0.3239). Our retrospective study shows that transfusional Fe overload is not rare among adults with SCD and develops predominantly as a result of episodic blood transfusions. This underscores the importance of the development and dissemination of evidence based guidelines, especially for episodic transfusions in SCD. A careful study of the extent and degree of organ damage associated with transfusional Fe overload in SCD and why less than half (46.2%) of patients are exposed to chelation therapy needs to be done. These studies should include liver iron concentration (LIC), cardiac iron and liver histology, when indicated, in parallel with serum hepcidin levels. The fact that the reduction in serum ferritin levels with deferasirox did not reach statistical significance in this cohort can be explained by the relatively small number of patients as well as by the short period (6 months) of exposure to chelation therapy. Disclosures: No relevant conflicts of interest to declare.

Hereditary Hemochromatosis in an Adult Due to H63D Mutation: The Value of Estimating Iron Deposition By MRI T2* and Dissociation Between Serum Ferritin Concentration and Hepatic Iron Overload

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4891-4891
Author(s):  
Mohamed A. Yassin ◽  
Ashraf T Soliman ◽  
Vincenzo Desanctis ◽  
Sandara Abusamaan ◽  
Ahmed Elsotouhy ◽  
...  
Keyword(s):  
Iron Overload ◽  
Basal Ganglion ◽  
Serum Ferritin ◽  
Normal Values ◽  
Hereditary Hemochromatosis ◽  
Transferrin Saturation ◽  
Iron Deposition ◽  
Ferritin Concentration ◽  
H63d Mutation ◽  
Serum Ferritin Concentration

Abstract Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive intestinal absorption of dietary iron, causing iron overload in different organs, especially the liver. Hemochromatosis may not be recognized until later in life. Patients are usually asymptomatic but may present with a variety of signs and symptoms. These include: hyper-pigmented skin, hepatomegaly, arthralgia, diabetes mellitusand/or heart failure/arrhythmia. The risk of HH related morbidity in HFE compound homozygotes patients (H63D /H63D) is considered rare, we report a male patient with H63D mutation who developed impaired glucose tolerance, and high hepatic enzymes due to significant iron accumulation in the liver as well as Parkinsonian-like syndrome due to iron deposition in the basal ganglia. A 40 year old Qatari male was referred for evaluation of a rise in hemoglobin and hematocrit values with normal MCV, total leucocyte and platelet counts. The patient was asymptomatic with normal vital signs, no depigmentation or hepato-splenomegaly. Hematologic findings included a hemoglobin concentration of Hb 16.5 g/dL, hematocrit 53%, mean corpuscular volume (MCV) 93 fL/red cell, leucocyte count of 7200/ μL and a platelet count of 199000/μL. His serum ferritin was 359 μg/l ( normal values: < 336 μg/l), serum iron: 37 μmol/l ( normal values <28.6μmol/l), fasting transferrin saturation: 64% (normal < 50%). A random glucose 6.5 and 6.4 mmol/L (normal values 5.5mmol/L ), A1C of 5,4 %, normal creatinine and electrolytes, alanine aminotransferase (ALT) of 66 U/l (normal < 40U/l), mild elevation of bilirubin 39 umol/l (normal <24umol/l), normal U&E Hepatitis B and C antibodies were negative. OGTT revealed impaired glucose tolerance. Thyroid function, morning serum cortisol, LH and FSH and serum total testosterone concentrations were in the normal range. A diagnosis of polycythemia vera was excluded on the basis of WHO Criteria 2008. The polymerase chain restriction assay was negative for the common mutation (C282Y) but positive for H63 D mutation. Family screening confirmed HH in his brother (homozygous), whereas his mother, two brothers and the sister were carriers (heterozygous). His four offspring were carriers. This suggested an autosomal recessive mode of inheritance. Conventional MRI study showed a normal liver size with diffuse fatty changes and focal areas of fatty sparing with some evidence of iron deposition. Whereas, T2-star (T2*) sequences showed a diffuse and significant decrease in liver signal intensity. A LIC liver concentration of 27 mg Fe/g dry wt was found (normalvalues:< 2 mg Fe/g dry wt; severe iron overload: ≥15 mg Fe/g dry wt). No significant iron deposition in the spleen, heart or pancreas was observed. At the age of 41 years the patient complained of tremors in both hands and arms while sitting or standing still (resting tremor) that improved with hands movements. A brain MRI revealed iron deposition in the basal ganglion. It was concluded that basal ganglionicn iron deposition mediated the neurological decline. Currently, the transferrin saturation and serum ferritin levels are within normal. Discussion: This is the first case of HH secondary to H63 D among an Arab family and the first reported case of Parkinsonism tremors secondary to this mutation. The H63D HFE variant is less frequently associated with HH, but its role in the neurodegenerative diseases has received a great attention. An accurate evaluation of iron overload is necessary to establish the diagnosis of HH and to guide iron chelation in HH by determination of liver iron concentration (LIC) by means of T2* MRI. Although serum ferritin concentration was only mildly increased a significant siderosis in the liver was detected by MRI T2* technique occurred. Liver siderosis was associated with mild impairment of liver function (increased serum ALT and bilirubin ). Conclusion: Our data further confirm that serum ferritin levels are not an accurate measure of total body iron stores in HH. Iron deposition in the liver and basal ganglion occurred despite mild elevation of ferritin. changes in basal ganglion may present by parkinsonian like tremors in these patients Use,T2* MRI should be encouraged in patients with HH for better evaluation of Iron overload and avoidance of Complications since serum ferritin can be misleading in these conditions. Disclosures Yassin: Qatar National research fund: Patents & Royalties, Research Funding. Aldewik:Qatar Ntional Research Fund: Patents & Royalties, Research Funding.

scholarly journals Correlation between serum ferritin level, cardiac and hepatic T2-star MRI in patients with β-thalassemia major in Al-Diwaniya thalassemia center

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Alaa Mutter Jabur Al-Shibany ◽  
AalanHadi AL-Zamili
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Iron Level ◽  
The Mean ◽  
T2 Mri

Patients with transfusion dependent thalassemia major is often associated with iron overload. Proper use of iron chelators to treat iron overload requires an accurate measurement of iron levels. Magnetic resonance T2-star (T2* MRI) is the preferred method to measure iron level in the liver andthe heart. The goal of our study was to see if there is an association exists between serum ferritin level and T2* MRI results in patients with beta thalassemia major.This study was done in Al-Diwaniya Thalassemia center,Maternity and children teaching hospital,Iraq. During the period from 1st of January to 31st of October. Fifty eight patients with a diagnosis of beta thalassemia major were enrolled in the study. They were older than five years old,transfusion dependent and on chelation therapy. Hepatic and Myocardial T2*MRI and the mean serum ferritin levels were measured during the study period for all patients.There is a significant correlation was observed between serum ferritin level and cardiac T2*MRI (p=0.018 ). also a significant correlation was observed between serum ferritin and hepatic T2*MRI (p=0.02). Neither cardiac T2* MRI nor hepatic T2* MRI show any correlation with the mean age.our study also showa positive correlation between the patients withcardiac T2* MRI and the development of diabetes mellitus in contrast to hepatic T2* MRI in which there is no any correlation. Hypothyroidism was observedno correlation with either cardiac or hepatic T2* MRI.Our results showed a positiveassociation between hepatic, cardiac T2*MRI and serum ferritin levels.

Iron Overload and Haematopoiesis in MDS: Does Blood Transfusion Promote Progression to AML?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2685-2685 ◽  
Author(s):  
Lap Shu Alan Chan ◽  
Rena Buckstein ◽  
Marciano D. Reis ◽  
Alden Chesney ◽  
Adam Lam ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Bone Marrow Cells ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Ferritin Concentration

Abstract Introduction: The biology of myelodysplastic syndrome (MDS) is poorly understood, and treatment options are limited. Thus, most MDS patients require chronic red blood cell transfusion, and many develop secondary iron overload. Although the pathophysiological consequences of iron overload to the heart, liver, and endocrine organs have been well characterized, its effects on haematopoiesis have not been studied. However, it has been observed that chelation therapy in iron-overloaded MDS patients may result in reduction of transfusion requirements, and recent studies have suggested a correlation between the use of iron chelation therapy and improvement in leukaemia-free survival in MDS. At the cellular level, iron toxicity is mediated in large part via the generation of reactive oxygen species (ROS). It has been shown in animal models that accumulation of ROS leads to senescence of haematopoietic stem cells, and that ROS cause DNA damage and promote the development of malignancy. These effects of ROS may be particularly important in MDS, in which haematopoiesis is already severely compromised and genetic instability is a striking feature. Hypothesis: We hypothesize that iron overload secondary to transfusion leads to increased levels of intracellular ROS in early haematopoeitic cells in MDS. The increase in intracellular ROS in MDS would be predicted to lead further impairment of haematopoiesis via stem cell exhaustion and while promoting accumulation of DNA damage by myelodysplastic stem cells and early progenitors, thus accelerating progression of MDS to acute leukaemia. Results: To test this hypothesis, we examined the relationship between transfusion-related iron overload and ROS content of CD34+ bone marrow cells in MDS. ROS content was measured in CD34+ cells by flow cytometry in bone marrow aspirates from 34 consecutive MDS patients (CMML=4, MDS/MPD=2, RA=4, RARS=3, RCMD=2, RAEB 1=6, RAEB 2=12, RAEB-t/AML=1). The patients represented a wide range of prior transfusion burden (0-&gt;300 units PRBC) and serum ferritin levels (11-&gt;10000 μg/L). ROS was strongly correlated with serum ferritin concentration for patients with iron overload (serum ferritin &gt;1000 μg/L; n=14, R=0.733, p&lt;0.005). The correlation between ROS and ferritin level was even stronger in the subset of patients with RAEB 1 or RAEB 2 and iron overload (n=11, R=0.838, p&lt;0.005). In contrast, no correlation between ROS and ferritin level was demonstrated for patients with serum ferritin &lt;1000 μg/L (n=20). Importantly, iron chelation therapy was associated with a reduction in CD34+ cell ROS content in one patient. To assess the effect of iron overload on normal stem cell and progenitor function, we established a mouse model of subacute bone marrow iron overload. B6D2F1 mice were loaded with iron dextran by intraperitoneal injection (150mg total iron load over 21 days), and sacrificed three days after the end of iron loading. Iron staining of tissue sections confirmed iron deposition in the bone marrow, liver, and myocardium. The development of splenomegaly was noted in iron-loaded animals. Flow cytometric analysis revealed increased apoptosis of bone marrow cells in iron loaded mice based on annexin V+/7 AAD-staining (6.26±0.96% versus 3.54±0.99% for control mice, paired student’s t-Test p&lt;0.005). However, ROS content in CD117+ progenitors of iron loaded mice was similar to control mice. Thus, subacute iron loading in mice increases apoptosis but does not alter the ROS content of HSCs; we postulate that chronic iron overload is required to achieve this effect. Conclusions: These results establish a relationship between CD34+ cell ROS content and serum ferritin concentration in MDS patients with iron overload, and indicate that iron chelation therapy in this patient population reverses this ROS accumulation. The physiological consequences of this relationship are currently being investigated in this patient set by haematopoietic colony assays and assessment of DNA damage in CD34+ cells. Nonethelesss, these data may have key implications for the deployment of iron chelation therapy in MDS patients, and may explain the association between the use of iron chelation and improved leukaemia-free survival in MDS.

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