Nghiên cứu tình trạng nhiễm sắt và kết quả điều trị thải sắt của bệnh nhân thalassemia TT TIẾNG ANH

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY PHAM THI THUAN STUDY ON THE IRON OVERLOAD AND THE RESULTS OF IRON CHELATION THERAPY IN PEDIATRIC THALASSEMIA PATIENTS Specialty: Pediatrics Code: 62720135 SUMMARY OF THESIS OF PHILOSOPHY DOCTOR OF MEDICINE HANOI - 2022 Completed at HANOI MEDICAL UNIVERSITY Science Instructor ASSOCIATE PROFESSOR BUI VAN VIEN Critic 1: Associate professor PhD Nguyễn Ngọc Sáng - Hai Phong University of Medicine and Pharmacy Critic 2: Associate professor PhD Lê Xuân Hải - National Institute of Hematology and Blood Transfusion Critic 3: PhD Dương Bá Trực - Vinmec International General Hospital The thesis has been defended at University - level Thesis Evaluation Council, held in Hanoi Medical At………hour ., day………month………2022 This thesis may be found at: - National Library - Central Medicine Information Library - Library of Hanoi Medical University University List of announced research projects related to thesis Pham Thi Thuan, Bui Van Vien (2017) Determination of iron overload in pediatric thalassemia patients at Clinical Hematology Hematology at the National Children's Hospital Journal of 108 Clinical Medicine and Pharmacy, 12(5), 54-58 Pham Thi Thuan, Bui Van Vien (2017) Efficacy of oral chelation therapy with deferiprone on pediatric thalassemia patients at the National Children's Hospital Journal of 108 Clinical Medicine and Pharmacy, 12 (special issue), 273-278 BACKGROUND OF THESIS Urgent nature of the thesis Thalassemia is the most common hereditary hemolytic disease in the world, about 7% of the world's population carries the disease gene In Vietnam 2017, there are over 12 million people carrying the thalassemia gene, and each year about 8000 babies are born with thalassemia Periodic blood transfusion helps control anemia but also causes gradual accumulation of iron, if this condition is not treated appropriately, it will cause serious complications in cardiovascular, endocrine, and death for the patient Many developed countries used magnetic resonance imaging (MRI) to measure the amount of iron in the heart and liver routinely At the same time, oral chelation drug deferiprone (DFP) is used to treat iron overload due to its effectiveness, safety and low cost In Vietnam, there have been no studies using MRI to measure iron in the liver and heart to assess iron overload and monitor the effectiveness of deferiprone chelation therapy in pediatric thalassemia patients Therefore, I carried out a research project: "Study on iron overload and results of iron chelation therapy in pediatric thalassemia patients", for purposes of: Evaluation of iron overload in pediatric thalassemia patients at the National Children's Hospital from 2014 to 2016 Evaluation of the results of iron chelation therapy with deferiprone of pediatric thalassemia patients with iron overload at the National Children's Hospital from 2014 to 2016 Practical signification and new contributions of the thesis Practical signification of the thesis: - Multiple methods can be used to assess iron accumulation: by serum ferritin index, liver iron overload and heart T2* time by T2* MRI - Assessing the iron accumulation as well as monitoring the effectiveness of chelation therapy for thalassemia patients, helps to promptly prevent serious complications of iron overload Scientific contributions - Applying the new technique MRI T2* accurately assesses iron overload in the liver and heart, as well as monitors the results of chelation therapy for thalassemia patients - The oral chelator deferiprone is effective and safe in the treatment of hepatic and cardiac iron accumulation and in reducing serum ferritin levels in pediatric thalassemia patients who are undergoing periodic blood transfusion Thesis structure This thesis covers 120 pages, including: background (2 pages), literature overview (33 pages), materials and methods (17 pages), study results (27 pages), discussion (38 pages), conclusions (2 pages), recommendation (1 page) The thesis consists of 47 tables, 13 charts, 11 pictures There are 147 references, with 130 in English, 17 in Vietnamese, the publication dates are almost within 10 years recent Appendix includes documents, pictures of liver, heart MRI, list of patients, samples of study records CHAPTER 1: LITERATURE OVERVIEW 1.1 Thalassemia Thalassemia is an inherited syndrome of hemoglobin (Hb) disorders, resulting from a deficiency in the synthesis of one or more polypeptide chains in the globin of Hb Depending on the deficiency of alpha (α), beta (β) or both delta (δ) and β chains, it is called alpha thalassemia (α - thal), beta thalassemia (β thal), or delta beta thalassemia (δβ - thal) The gene that synthesizes globin chains of the α family is located on the short arm of chromosome 16 and the gene that synthesizes the globin chains of the β family is located on the short arm of chromosome 11 The pathogenesis of thalassemia is due to an imbalance in the synthesis of α and non-α globin chains result to shortening the life of erythrocytes, premature destruction of red blood cells in the bone marrow In order to monitor and treat thalassemia patients better, from 2012 onward, based on the patient's level of transfusion dependence, thalassemia was classified into transfusion dependent thalassemia (TDT) and thalassemia Nontransfusion 1.2 Thalassemia treatment - Blood transfusion therapy - Iron chelation therapy - Slenectomy - Other treatments: Drugs to increase fetal Hb synthesis (hydroxyurea, busulfan ), allogeneic hematopoietic stem cell transplantation, gene therapy, supportive therapy 1.3 Iron overload in thalassemia patients and methods to assess iron overload Thalassemia patients develop iron accumulation from blood transfusions, or from increased gastrointestinal iron absorption Iron overload is the main cause of many complications, reducing the quality of life as well as the life expectancy of thalassemia patients: myocardial siderosis, cirrhosis, endocrine glands damage due to iron overload causing diabetes, delayed puberty, hypogonadism, hypothyroidism in patients who not receive chelation Picture 1.1 Distribution and consequences of transfusional iron overload Assessment of body iron can be based on quantitative serum ferritin (SF), liver biopsy to measure the amount of iron in the liver (LIC), using MRI T2* to measure the amount of iron in body’s organs (liver, heart, endocrine glands) 1.4 Treatment of iron overload When to start iron chelation therapy - After the first 10 - 20 transfusions or transfused more than year - When the ferritin level rises above 1,000 µg/l - Should start after years of age Practical prescribing of individual chelators There are three iron chelators currently used: desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX)  The average doses should not exceed 40 mg/kg The standard dose is 2040 mg/kg for children, and up to 50-60 mg/kg for adults, as an 8-12-hour subcutaneous infusion for a minimum of nights per week  The standard dose of DFP is 75 mg/kg/day, given in three doses Ajustments may be made on the basis of the patient’s response but should never exceed 100 mg/kg/day  When monotherapy with DFO or DFP is inefficient, we can be used combination therapy with DFP and DFO  DFX: 20 mg/kg/day is recommended for thalassaemia major patients with iron loading 0,3-0,5 mg/kg/day For patients with iron loading >0,5mg/kg/day, 30mg/kg/day is recommended For patients with iron loading ( 0,05 14 Chart 3.5: Changes in the proportion of iron overload according to SF, LIC, heart T2* before and after DFP chelation therapy Comment: After year of chelation with DFP, there was an improvement in iron overload severity based on SF, LIC and heart T2* of the study patients Evaluating by SF, the proportion of patients with severe and moderate iron overload decreased by 43,1% to 36,9% and 36,9% to 23,1%, respectively Based on LIC, the proportion of patients with severe iron overload decreased from 50,7% to 26,2% Assessing iron overload according to heartT2*, the proportion of patients with severe cardiac iron overload increased after treatment, increasing from 6,2% (4 patients) to 7,7% (5 patients) 3.3.4 Characteristics of responder and non-responder group to DFP chelation therapy Dividing the study patients into groups: the responder group to DFP chelation therapy (with a decrease in LIC after year of treatment) - accounting for 71%, and the non-responder group (LIC increases after year of treatment) accounted for 29%, to preliminary evaluate the characteristics of these groups Table 3.10: Characteristics of responders and non-responders to DFP chelation therapy Responders Non-responders Index p LIC (mg/g dw) - baseline Iron load (mg/kg/day) (n=46) (n=19) 17,3 ± 6,42 0,42 ± 0,210 13,7 ± 5,63 0,58 ± 0,285 0,021 0,013 15 Comment: The group that responded to DFP chelation therapy had a higher LIC baseline and a lower iron load than the non-responder group, the differences were statistical significant with p = 0,021 and p = 0,013 3.3.5 Adverse side effects of DFP in study patients Table 3.11 Rate of common adverse events due to DFP in study patients ADR Number of patients Incidence (%) Neutropenia 4,6 Increased ALT 12,3 Joint pain 10,8 Digestive disorders 12,3 General 13 20 Comment: When using oral iron chelation drug DFP, 13 patients (20%) experienced side effects such as increased ALT, digestive disorders, joint pain, only 3/65 (4,6%) patients had this condition neutropenia There were 52 (80%) patients in the study without any side effects of the drug CHAPTER 4: DISCUSSION 4.1 General characteristics of study patients Thalassemia is an inherited hemoglobin disorder associated with mutations in the synthesis of globin chain genes located on chromosomes 11 and 16 In this study, the prevalence in male was 57,8% higher than in female 42, 2%, similar data in other studies In our study, the group of patients with HbE/β-thal accounted for the highest proportion - 49,5%, β-thal accounted for 41,3% and HbH accounted for 9,2% Study patients were transfusion-dependent thalassemia, so the age of onset of the disease and the age of starting blood transfusion is quite early - 1,7 years old The average age of study patients was high – 7,3 years old Study patients had a low pre-transfusion Hb concentration of 66,3g/l Patients had a long duration of transfusion therapy at the begining time of study, with a median of 6,8 years There were 68,8% patients who received previous chelation therapy with all types of chelating agents DFO, DFP and DFX with the respective rate of 11,9%, 38,5% and 18,3% (in which is mainly chelation with DFP - 38,5%) Our study recorded that the rate of patients infected with hepatitis C virus was quite high at 68,8%, only 0,9% of patients were infected with hepatitis B virus 16 4.2 Evaluation of iron overload of thalassemia patients in the study 4.2.1 Some clinical manifestations of patients in the study Thalassemia patients always have iron overload due to hemolysis, blood transfusion, and increased iron absorption Iron overload manifestations such as hyperpigmentation, hepatomegaly, and bone deformities account for a high rate of 81,6%, 87,1% and 83,5%, respectively The proportion of splenomegaly was 51/67 patients without splenectomy, accounting for 76,1% Our data are similar to those of the others: Nguyen Cong Khanh - 1993, up to 88% of HbE/β-thal patients have hepatomegaly, the proportion of patients severe β-thal and HbE/ βthal with enlarged liver, hyperpigmentation were 34% and 64%, respectively; Bui Van Vien, there was 79,2% of HbE/β-thal patients with hepatomegaly, the proportion of severe β-thal patients with hyperpigmentation was 53,6% and 96,1% HbE/ β-thal patients had splenomegaly; the study of Duong Ba Truc on 46 HbH patients showed that 60,8% had facial bone deformities, 89,1% had splenomegaly According to McDonaugh - 1993, all severe β-thal patients who did not receive adequate blood transfusion had bone deformities 4.2.2 Assessing the severity of iron overload of thalassemia patients The International Thalassemia Federation recommended SF, MRI T2* to measure liver iron concentration (LIC) and cardiac siderosis to assess iron overload and monitor during iron chelation therapy The results in chart 3.2 showed that the majority of patients have iron overload according to SF and LIC, mainly moderate to severe; only a small number of patients have cardiac iron overload The average SF of study patients was 1954 ng/ml, our study data are lower than some other authors: according to Nguyen Thi Hong Hoa studied on 30 transfusion dependent thalassemia (TDT) patients with an average age of 10 years, the mean SF was 2926 ng/ml Study of Wahidiyat - 2017, on 162 thalassemia major patients with average age of 14 years, the mean SF was 3793 ng/ml Thus, the older the patient was, the more severe the iron overload affected LIC index showed that the majority of study patients had liver iron overload (99,1%), with moderate to severe, 38,5% and 49,6%, respectively The average LIC of study patients was 14,7 mg/g dw Our results are lower than some others: Nguyen Thi Thu Ha studied on 83 TDT patients had an average LIC of 20,97 mg/g dw Wahidiyat - 2017, studied on 162 thalassemia major patients, 17 showed the average LIC was 15,5 mg/g dw This difference may be because we studied on children, so the liver iron overload was milder than that of adults MRI T2* showed that most patients - 87,2% did not have myocardial siderosis with T2* ≥20ms, however, there were still 4,6% of patients with severe myocardial iron overload with T2* < 10ms The mean heart MRI T2* of study patients was 27,6ms Compared to some other studies, our data were different: Wood et al - 2008, studied TDT patients aged from 2,5 to 18 years old, heart T2* < 20ms was encountered in 24% and 36% of patients aged 9,5-15 and 15-18 years respectively The multicenter study of Casale - 2015 showed that the heart T2* in TDT patients was 32,8ms and 21,5% of TDT patients had heart T2* < 20ms Heart MRI T2* < 20 ms has prognostic value for severe cardiac complications (especially heart failure) in patients with thalassemia major: Risk of heart failure within one year increased from 0,2% in patients with T2 * = 10 to 20 ms, to 21,4% in patients with T2 * = to 10 ms, and finally to 47,23% in patients with T2 * = to ms Therefore, patients with low heart T2* should receive enhanced chelation therapy to avoid the risk of serious cardiac complications 4.2.3 Manifestations of heart damage of thalassemia patients Evaluation the decline in myocardial contractility based on LVEF - table 3.3 showed that 100% of patients did not show signs of decreased myocardial contractility Thus, if only using LVEF to check the heart iron overload of thalassemia patients will eliminate the affected cases, especially the severe heart iron overload cases (4,6% were found in our study patients) Although the study patients did not show any decline in myocardial contractility, however, up to 13,5% of patients showed arrhythmias on electrocardiogram - ECG (table 3.4) Research of Neha - 2016 on 60 children with thalassemia major showed that up to 51,6% of patients had abnormal ECG manifestations Arrhythmias due to myocardial iron overload in thalassemia patients can begin early, most patients are asymptomatic but may present abnormal on the ECG, therefore regular monitoring of the ECG is recommended for early detection and appropriate treatment cardiovascular events to improving iron chelation efficiency and improving the quality of life for these patients 4.2.4 Assess the severity of iron overload by thalassemia type Table 3.5 showed that β-thal patients have the most severe iron overload by SF, LIC indexes compared to the other types and the cardiac iron overload of 18 patients with all thalassemia types is not statistically significant different This is because in TDT group, patients with homozygous β-thal often have the most severe clinical manifestations, the blood transfusion regime of these patients is often higher than the other groups, resulting in more severe iron overload as shown by higher SF and LIC indexes compared to the other types When there was an iron overload, the liver will be the first organ affected, then other organs such as the heart and endocrine glands, so there was no difference in the manifestation of heart iron overload in the initial period 4.2.5 The correlation between serum ferritin, LIC, heart T2* and LVEF Research data showed that there was a high degree of positive correlation between SF and LIC with r = 0,583 (chart 3.2) Our study data are similar to those of others: Majd - 2015 who studied on 87 TDT patients and found a strong positive correlation between SF and LIC with r = 0,718; Casale - 2015 studied on 107 children with thalassemia major found that SF was positively correlated with LIC with r = 0,668 Chart 3.3 showed that there was a negative correlation between SF and heart T2* at an average level (r = - 0,348) Our results are similar to those of others: Azarkeivan - 2013 studied on a group of 156 β-thal patients with severe SF found that there was negative correlation with heart T2* values (r = - 0,361); Casale – 2015 studied on 107 children with thalassemia major found that SF was negatively correlated with heart T2* value (r = - 0,425) There was a high degree of positive correlation between SF and LIC; and a moderate negative correlation between SF and heart T2* in study patients Thus, to accurately determine the iron overload in liver, heart we must take MRI T2*, if this technique cannot be performed, we can use SF to monitor iron overload, although it is impossible to accurately measure the amount of iron deposited in the tissues (liver, heart), but it can predict the tendency of iron deposition Chart 3.4 showed that there was a negative relationship between LIC and heart T2* at a weak level (r = - 0,29) Our results are different from other authors: Casale - 2015 found that LIC was a moderate negative correlation with heart T2* (r = - 0,436); Nguyen Thi Thu Ha in 2017 also found a negative correlation between LIC and heart T2* in thalassemia patients r = - 0,36 The causes of this condition may be due to: liver iron overload often occurs first, cardiac tissues and 19 endocrine glands often become iron overload more slowly due to different iron absorption mechanisms At the same time, the rate of iron heart chelation is usually slower than in the liver, active chelation can rapidly and completely remove iron liver within months, but heart chelation may take several years; in some cases, after a period of chelation, the patient may have high cardiac iron accumulation and low LIC 4.2.6 The association between the indicators to assess the severity of iron overload serum ferritin, LIC and heart T2* According the International Thalassemia Federation - 2008, 70% of patients with SF > 2500 ng/ml (severe iron overload) for more than one year will have an increased risk of cardiovascular complications, while patients with SF < 1000 ng/ml (mild iron overload) would not present this risk Table 3.6 showed a relationship between severe liver iron overload, SF levels and heart iron overload Severe liver iron overload and heart iron overload in the group with SF ≥ 2500 ng/ml were 2,1 and 2,7 times higher, respectively, than in the group with SF < 2500 ng/ml, the differences were statistically significant with p < 0,05 There was a relationship between heart iron overload and severe liver iron overload, heart iron overload in the severe liver iron overload group was 10,8 times higher than the remain, the difference was statistically significant with p < 0,01 Thus, maintaining SF at < 2500 ng/ml reduces the risk of severe liver and cardiac iron overload Maintaining LIC < 15 mg/g dw reduces the risk of cardiac iron overload 4.3 Evaluation of the results of iron chelation therapy with DFP 4.3.1 General characteristics of patients treated with DFP Table 3.7 showed that the age of onset and initiation of blood transfusion of study patients were quite early, with a mean age of 1,7 years; the average age of patients at the initial study was 7,5 years old, so patients had a long duration of previous blood transfution therapy - 6,8 years on average, therefore, they used previous chelators as recommended DFO, DFX and DFP When participating in the study, patients were treated with DFP iron chelation therapy at the recommended dose: the average DFP dose was 70.8mg/kg/day 4.3.2 Iron load from blood transfusion of study patients According to table 3.8, the iron load from blood transfusion regime of our study patients were quite high, averaging 0.49mg/kg/day, in which mainly 20 patients with moderate and high transfusional iron load According to Angelluci's estimate, if thalassemia patients receive periodic blood transfusions and not receive annual chelation therapy, an additional amount of iron will accumulate in the liver: ∆ LIC (mg/g dw) = Transfusion iron load (mg/kg/year)/10,6 Iron burden due to blood transfusion is closely related to the frequency, volume and duration of transfusion therapy, with such high iron load from transfusion inevitably leading to iron deposition in organs If untreated with chelation, excess iron will accumulate in the body every day, causing serious complications such as cirrhosis, heart failure, hypogonadism, etc for thalassemia patients 4.3.3 Evaluation of the effect of DFP on serum ferritin, liver iron overload and cardiac iron overload Study data in table 3.9 and chart 3.5 showed: after year of follow-up of iron chelation therapy with DFP, there was a decrease in iron overload indicators and severity of tissues iron deposit: decreased SF, decreased LIC, increased heart T2*, increased LVEF of patients compared with baseline Thus, our study proved that DFP is effective in the treatment of iron overload in pediatric thalassemia patients Literature also showed that DFP was effective in reducing iron overload through reducing SF index after 12 months of treatment similar to DFO, and at the same time after year of treatment with a dose of DFP 75 mg/kg/day about one-third of TDT patients receiving standard blood transfusions achieve negative iron balance and reduce LIC, DFP is more effective than DFO in removing iron from the heart, improving myocardial contractile function Table 4.1 Compare the effectiveness of DFP on SF reduction Number Study SF DFP dose SF ending Study of duration baseline (mg/kg/day) (ng/ml) (month) (ng/ml) patients 65 75 12 1852 1398 This study N.T.M.Lan 32 75 3-15 1741 1396 2014 El-Alfy 100 75 12 2532 2176 2010 Viprakasit 73 79 12 3194 3088 2013 DEEP-2 137 75 - 100 12 2468 2120 2020 21 The effectiveness of DFP on SF reduction in our study was similar to other studies The results are shown in table 4.1 Comparing the effectiveness of reducing iron accumulation in the liver, our results are similar to those of other authors: Aydinok's study showed that after year of chelation therapy with DFP the patient's LIC decreased from 30,7 mg/g dw to 28,6 mg/g dw; El-Beshlawy's study found that the patient's LIC decreased from 15,8 mg/g dw to 7,5 mg/g dw; the GPO-L-ONE study of 73 pediatric TDT patients receiving iron chelation with DFP in Thailand - 2013, showed a reduction in LIC in 45,2% of SF-reducing responders, and a greater reduction in SF in pediatric patients with higher LIC baseline DFP effectively increased heart T2* from 26,3 ms to 34,6 ms, the difference was statistically significant with p < 0,01, which corresponds to a reduction in the heart iron deposited, however, this beneficial change was only statistically significant in the group T2* ≥ 20ms The proportion of patients with severe cardiac iron overload increased after year of chelation from 6,2% (4 patients) to 7,7% (5 patients) This may be due to, iron removal from the heart occurs more slowly than from other organs Active chelation can remove iron from the liver quickly and completely in months, but the chelation process in the heart can took several years Thus, if patients already have cardiac iron overload T2* < 20ms, only chelation therapy with one iron chelator, DFP at a dose of 75mg/kg/day, will not be effective It is necessary to enhance chelation therapy by increasing the dose of DFP or using combination regimens in these patients 4.3.4 Characteristics of responder and non-responder group to DFP chelation therapy To evaluate whether patients respond or not to chelation therapy, our study used LIC: study data showed that 71% of patients had a response to reduce LIC after year of chelation therapy by DFP The responder group to DFP had a higher baseline LIC than the nonresponder group, 17,3 and 13,7 mg/g dw, respectively; and the mean iron load from blood transfusion in the responder group was lower than in the nonresponder group, 0,42 and 0,58 mg/kg/day, respectively (table 3.10) These proved that the iron load plays a particularly important role in the treatment of iron chelation With the same chemotherapeutic regimen even in patients who 22 initially had more severe hepatic iron accumulated (the responder group with LIC 17,3 mg/g dw), but with a transfusional iron load lower (iron load 0,42 mg/kg/day) had a better LIC reduction than the group with milder hepatic iron overload but with a higher iron load (LIC - 13,7mg/g dw, iron load 0,58 mg/kg/day) Thus, the more blood transfusion patients received, the greater iron cumulated, so we need to adjust the dose of iron chelation therapy appropriately for patients with different rate of iron load To ensure the effectiveness of chelation therapy, patients with high transfusional iron should be given an enhanced chelation regimen: increasing the dose of DFP to a maximum of 100mg/kg/day or combine other chelation drugs (DFO or DFP) 4.3.5 Adverse side effects of DFP in study patients The data in table 3.11 showed that: 52 patients (accounting for 80%) did not have any side effects of the drug The study encountered some side effects such as increased ALT, digestive disorders, joint pain, these were usually mild, resolved without treatment, however 3/65 patients (accounting for 4,6%) had neutropenia Studies on the safety of DFP in children, especially in children under 10 years of age, are very limited, the multicenter study DEEP-1 (2017) conducted on 18 children aged to years showed that DFP safe for children under years of age with a dose of 25mg/kg/time times a day, similar to older children and adults Another study DEEP-3 (2018) in 297 patients with a mean age of 8,5 years (0,6-17,6 years), showed that DFP is safe for children DEEP-3 reported 14,8% of patients presenting with Adverse Drug Reactions (ADRs), where DFPassociated granulocytopenia was identified in 25 non-splenectomy patients (incidence - 8,4%) Gastrointestinal symptoms (nausea, vomiting, and abdominal pain occurring with an incidence ranging from 0,3% to 3,4%, without severe ADRs, the median time from drug administration to the onset of gastrointestinal ADR was months ALT elevation was observed in 31 patients (incidence 10,4%), median time to onset of this manifestation was months Manifestation of pain and swelling of joints, mainly in the knee joint, were seen in 35 patients (11,8%) The DEEP-2 (2020) study, which collected safety information data from a total of 194 pediatric patients to 18 years of age who treated with DFP, showed that DFP is as effective in reducing SF and as safe as DFX for pediatric TDT, the most common ADR manifestations are gastrointestinal symptoms - 23 26%, the proportion of patients with arthralgia is 12%, the rate of patients with agranulocytosis is 9%, ALT elevation is seen in 5% of patients Adverse reactions disappear when DFP is stopped, dose is reduced, or even without intervention Study results have shown that oral chelation therapy with DFP effectively reduces iron overload in body tissues (liver, heart) and reduces SF The drug is safe and has few side effects However, the improvement of the iron status of the tissues is often slow (especially in the heart) Therefore, it is necessary to persist in long-term iron chelation therapy, and at the same time, it is necessary to periodically evaluate iron overload in the liver and heart by MRI to monitor the effectiveness of chelation therapy earlier CONCLUSIONS Evaluation of iron overload of study patients Patients in the study had a high proportion of iron overload: - Evaluation of iron overload by serum ferritin (SF) index: 97,2% had iron overload, mainly moderate to severe with the propotion of 42,2% and 37,6%, respectively The SF of the study patients was high, the average was 1954 ng/ml - Evaluation of liver iron overload by LIC: 99,1% of patients had liver iron overload, the proportion of thalassemia patients with moderate to severe liver iron overload was 38,8% and 49,6% respectively The average LIC of study patients was 14,7 mg/g dw - Evaluation of cardiac iron overload by MRI T2*: 12,8% of the study patients had myocardial iron overload with T2* < 20ms, 4,6% of patients had severe iron overload with T2* < 10ms The mean heart MRI T2* of patients was 27,6ms - There were correlations between the indicators of iron overload: SF and LIC had a high degree of positive correlation; SF and cardiac iron overload heart MRI T2* had a moderate negative correlation; and LIC and heart MRI T2* had a a weak negative correlation - In patients with severe iron overload by SF ≥ 2500 ng/ml, the risk of severe liver iron overload was 2,1 times higher and cardiac iron overload was 2,7 times higher than the group with SF < 2500 ng/ml In patients with severe liver iron overload, the risk of heart iron overload was 10,8 times higher than the group without it 24 Deferipron was effective in reducing iron overload in study patients - Oral iron chelation therapy with deferiprone for year was effective in reducing iron overload: mean serum ferritin decreased 459 ng/ml, mean LIC decreased 4,7 mg/g dw, increased heart MRI T2* average 8,1 ms compared to baseline - Severe and moderate iron overload decreased after year of chelation therapy with deferiprone: based on SF the proportion of patients with severe and moderate iron overload decreased from 43,1% to 36,9%, respectively, and 36,9% down to 23,1%; based on LIC the proportion of patients with severe iron overload decreased from 50,7% to 26,2% - Evaluation of treatment response through LIC index showed that after year of treatment, up to 71% of patients had a reduced response to LIC, the responder group had a lower iron load than the non-responder group - For patients with high transfusional iron load, enhanced chelation therapy with a dose of DFP 75-100 mg/kg or in combination with other chelation drugs is recommended - DFP was safe, few side effects and well tolerated: only 4,6% of patients withdrawn due to complications of neutropenia RECOMENDATIONS Based on the results of the study and discussion, we would like to give the following recommendations:: It is necessary to perform MRI T2* liver and heart for thalassemia patients periodically every 6-12 months to diagnose early, accurately the level of iron overload and monitor the results of chelation therapy to adjust the regimen for suitable for each patient Iron chelation therapy with deferiprone in children is effective, safe, and economical and should be widely used Further studies on thalassemia patients need to be continued over the longer term and in multiple groups of thalassemia patients An increased DFP dose or in combination with other chemotherapeutic agents should be considered in non-responders, high transfusional iron load or have cardiac iron overload ... treat thalassemia patients better, from 2012 onward, based on the patient's level of transfusion dependence, thalassemia was classified into transfusion dependent thalassemia (TDT) and thalassemia. .. (α), beta (β) or both delta (δ) and β chains, it is called alpha thalassemia (α - thal), beta thalassemia (β thal), or delta beta thalassemia (δβ - thal) The gene that synthesizes globin chains... load 3.2.3 Assess the severity of iron overload by thalassemia type Table 3.5: Assess the severity of iron overload by thalassemia type Heart T2* Thalassemia type SF (ng/ml) LIC (mg/g dw) (ms) HbH