BTM Patients Research Articles

Relationships Of Vitamin D And Vitamin B12 With Malonaldehyde In Patients With Beta Thalassemia Major

Background: Beta thalassemia major (Cooley's anemia) is a congenital genetic blood disorder resulting from a deficiency of β-globin chains due to severe anemia that depends on continuous blood transfusions for survival. Patients suffer from hemoglobinopathy, infection, diabetes mellitus, growth retardation, enlargement and damage to the liver and spleen, bone marrow aplasia and delayed sexual maturity. This complication arises due to the accumulation of iron, the impairment of antioxidants from vitamins, and an increase in lipid peroxides (MDA).Objectives: The study aimed to evaluate vitamin D and B12 levels and their relationship with MDA, liver enzymes (AST, ALT, ALP), iron and (Total Billirubin, Direct Billirubin, Indirect Billirubin).Materials and methods: The samples of BTM patients under study were (100 samples), (50 samples) for both males and females. Patients' ages ranged from (2-30 years). While the control sample was (40), with (20 samples) for each of the two sexes. Their ages ranged from (2-30 years). Their disease was confirmed by blood tests, hemoglobin electrophoresis, DNA analysis, and elevated ferritin levels. Vitamin D and B12 levels were assessed by immunoassay. While (MDA, Fe, AST, ALT, ALP) and (Total Billirubin, Direct Billirubin, Indirect Billirubin) were evaluated by colorimetric methods.Results: Vitamin D and B12 levels decreased significantly (p≤0.05). While the levels of (MDA, Fe, AST, ALT, ALP) and (Total Billirubin, Direct Billirubin, Indirect Billirubin) increased significantly at (p≤0.05) in BTM patients compared with the control group. Where the effect of the disease according to the results was clear in patients with age.
 conclusion: Our results indicate that the weakness of the antioxidant systems (vitamin D and B12) with the increase in oxidative factors resulting from the complications of the disease led to the exacerbation of the disease with iron overload, causing an increase in the levels of liver enzymes in the blood, damaging the liver and spleen.

Biodegradable temporising matrix: use of negative pressure wound therapy shows a significantly higher success rate

The purpose of this case series was to evaluate the efficacy of a synthetic biodegradable temporising matrix (BTM; PolyNovo Biomaterials Pty Ltd, Australia) and compare the outcome of BTM patients with and without negative pressure wound therapy (NPWT). A retrospective chart review was conducted on patients admitted with deep full-thickness burns, traumatic or complex wound injuries treated with BTM. Electronic medical records and images were evaluated by a team of clinical professionals. Endpoints included: the measure of successful BTM integration; and comparison between patients treated with and without NPWT. Additional measures were BTM total surface area, BTM sites, timeliness of BTM application and any complications. A total of 28 patients were evaluated and 23 (82.1%) demonstrated overall successful BTM integration. Patients treated with BTM in conjunction with NPWT (n=16) demonstrated a significantly higher (p=0.046) integration rate compared to patients treated without NPWT (n=12) (93.8% versus 58.3%, respectively). Patients treated with BTM with NPWT continued to successfully integrate and sustain favourable outcomes despite the presence of severe infection or the development of haematomas. A significantly higher integration rate was demonstrated when BTM was used in conjunction with NPWT. The results of this study further support the efficacy of successful integration of BTM as a replacement for tissue loss in the treatment of deep, full-thickness burns, traumatic and complex wound injuries, and particularly favourable outcomes with the use of NPWT. To the best of our knowledge, this is the first reported case series comparing the clinical outcomes of BTM with and without the use of NPWT.

Investigation of the Wetting Properties of Thalassemia Patients' Blood Samples on Grade 5 Titanium Implant Surfaces: A Pilot Study.

Background and Objectives: Beta-thalassemia (BT) has a high prevalence in Mediterranean, Southeast Asian, and African countries. Studies stated that thalassemia is an endemic disease that causes significant health problems in Cyprus. This study aimed to measure the contact angle between the implant and blood samples from BT major patients and healthy individuals to compare the contact angles and wettability of Grade 5 titanium implant surfaces. Materials and Methods: Grade 5 titanium discs that were 10 mm in diameter were used since they mimic the surface of dental implants. Following receiving informed consent, blood samples were taken from the patients’ index fingers in each group with lancet needles and a photo of the contact angle between the blood samples and the titanium surface was taken; the collected blood was transferred to a titanium disc with a medical pipette. ImageJ software with a specific contact angle plugin was used for the contact angle measurements. Results: Theta-mean, theta-circular, and theta-ellipse values were compared between all groups, and no significant difference was found (p > 0.05). Conclusions: In this study, it was hypothesized that the patients’ rheological property of decreased deformability would affect the wettability of implant surfaces in vitro; however, no such finding was reached in this study. Since in-depth studies associated with dental implant success in BTM patients are absent in the literature and Cyprus is one of the Mediterranean countries with a high prevalence of BTM, this study was conducted to enrich the literature. While some systemic diseases may affect the contact angle between the implant surface and blood, it can be concluded that this condition was not present for BTM patients in our study. Last but not least, we emphasize that this experiment was done on a single surface type and the results can be totally different when using other surface types.

Assessment of orthodontic treatment needs in patients with β-thalassemia major and sickle cell disease.

Patients suffering from hemoglobinopathies may suffer from pathogic dental and orofacial features. This study aimed to assess the prevalence of malocclusion and the need for orthodontic treatment in patients with β-thalassemia major (BTM) and sickle cell disease (SCD). The study was conducted on 311 blood transfusion-dependent patients with BTM or SCD and 400 healthy individuals aged 10 to 16. The types of malocclusion were evaluated based on Angle's classification and Dewey's modification, and their oral habits were recorded using a questionnaire. The need for orthodontic treatment was assessed through the Dental Health Component of the Index of Orthodontic Treatment Need (IOTN), and the data were compared with normal participants. The Index of Orthodontic Treatment Need-Dental Health Component (IOTN-DHC) assessment showed that patients had a higher prevalence of objective need for treatment (IOTN grades 4 and 5) compared to healthy children. The prevalence of class II malocclusion was significantly higher in patients. Patients showed significantly less Angle's Class I malocclusion compared to normal participants. Oral habits were presented in 61%, 64.15% and 62.4% of normal participants, BTM and SCD patients, respectively. The higher prevalence of Angle's class II malocclusion and higher percentage of IOTN grade 4 and 5 among BTM and SCD patients reveal the importance of early orthodontic assessment and intervention in children with BMT and SDC.

The prevalence of undiagnosed thalassemia minor among primigravida pregnant women before 20 weeks of gestation.

Pregnancy-associated anemia is a widespread condition that can have varying impacts on both the mother and the developing fetus, depending on the level of hemoglobin in the mother's blood and the stage of pregnancy at which the anemia occurs. In Iraq, 27% of all registered thalassemia cases are thalassemia minor. Pregnancy may aggravate mild undiagnosed thalassemia early in pregnancy. The objective of the study was to access the prevalence of undetected thalassemia minor in primigravida women who received prenatal care before 20 weeks and to compare the demographic and socioeconomic characteristic features between women with iron-deficiency anemia (IDA) and those without any anemia. A total of 298 primigravida women who attended prenatal care at 20 weeks or less were recruited and their hematocrit level was assessed. Participants were segregated into two groups regarding the presence of anemia. Patients who had packed cell volume lower than 33% underwent iron study and standard Hb electrophoresis. Information about women's demographics, socioeconomic status, and family history of hereditary anemia were recorded. The participants had a mean age of 22.7 years, with an age range spanning from 16 to 43 years. 33.33% of 298 women had pathological anemia. All the participants exhibited microcytic anemia, with 26.85%, had confirmed IDA, whereas 6.71% had β thalassemia minor (BTM) phenotype. Both BTM and IDA patients frequently reported a positive family history of anemia at 80% and 68.7%, respectively, which was significantly greater than the control group at 39.9% (P = 0.001). No significant differences were seen between BTM and IDA in terms of age or socioeconomic status. Anemia due to undetected thalassemia minor was common among primigravida women. Screening for BTM carriers pregnant can help in monitoring their status, assessing the fetus's risk of developing thalassemia, and making a diagnosis in communities with high rates of consanguineous marriages, such as Iraq.

Pediatrik Beta Talasemi Major Hastalarında Endokrin Komplikasyonlar: Tek Merkez Deneyimi

Background: Our aim was to identify risk factors and clinical correlates of endocrine complications in β-thalassemia major (BTM) patients.Materials and methods: This was a retrospective study carried out in the pediatric hematology and pediatric endocrinology departments of a tertiary healthcare institution with the medical data of 249 children with BTM (108 females, 43.4%; 141 males, 56.6%) with a median age of 7.17 (2 -17.8) years. Baseline descriptive, clinical features including endocrine complications and laboratory data were noted. Correlation between the presence of endocrine complications and demographic, clinical, and laboratory variables were sought. The effects of age, gender, race, height, weight, and splenectomy on endocrine complications were evaluated separately in each complication group. Results: Vitamin D deficiency/insufficiency is the most common endocrine complication (41.7%). According to Turkish children, Syrian children had also significantly lower vitamin D concentration (p=0.001). At least one endocrinopathy was reported in the majority of BTM patients (67.9%). Accordingly, pubertal status (p=0.014) and Syrian nationality (p=0.007) had significant impacts on TSH levels. Syrian children and those with delayed puber-ty had greater likelihood for subclinical or evident hypothyroidism. The likelihood of suffering from at least one endocrine complication was higher in older children (p=0.042) and those with Syrian nationality (p=0.025)Conclusion: Disorders of endocrine and metabolic nature are common in children with BTM. Early detection and protocol-based multidisciplinary management of these disorders constitute the most suitable strategies to in-crease patients' quality of life. Surveillance, early detection and treatment, and collaborative follow-up with a multidisciplinary team are the key points in the reduction of the severity and frequency of endocrine complica-tions as well as optimization of therapeutic outcomes.

Occult Hepatitis B Virus Infection among β-Thalassemia Major Patients in Ahvaz City, Iran.

Occult Hepatitis B Infection (OBI) is a critical risk factor for triggering post-transfusion hepatitis (PTH), cirrhosis, hepatocellular carcinoma, and hepatitis B virus (HBV) reactivation, which β-thalassemia major (BTM) patients are at risk of it due to multiple blood transfusions. This study was aimed at determining the prevalence of OBI among BTM patients from Khuzestan Province, Iran. In this cross-sectional study, 90 thalassemia patients, who have received blood 36 to 552 times, participated referred to the Shafa hospital of Ahvaz city from January 2018 to April 2019. ELISA for determining serological markers (HBsAg, anti-HBc, anti-HBs, and anti-HCV) and real-time PCR for detecting HBV-DNA were performed; Nested PCR was conducted for DNA sequencing and determining the genotype of OBI case. Phylogenetic and statistical analyses were done by R package. Of 90 subjects enrolled in this study; 95.5% (86/90) were HBsAg negative, and the frequency of OBI among them was 1.16% (1/86). The anti-HBs, anti-HBc, and anti-HCV were detected in 80.00%, 7.78%, and 12.2% of patients, respectively. HBV-DNA was assessed at four HBsAg-positive subjects as well, and all of them were negative. The phylogenetic analysis showed that the detected HBV DNA in the OBI case belongs to the genotype D. This research, for the first time, demonstrated that OBI is present among β-thalassemia patients in Iran. Also, further studies are necessary to determine the actual prevalence of OBI among BTM patients in Iran to decisions concerning OBI screening, especially in transfusion centers.

Evaluation of the relationship between sociodemographic characteristics, quality of life, depression, drug compliance and biochemical parameters in patients with thalassemia major in Isparta

Aim: We aimed to evaluate the quality of life and depression levels of BTM patients in our unit, to determine the relationship between each parameter and evaluate the demographic characteristics, laboratory data, and treatment compliance. Materials and Methods: Twenty-seven BTM patients aged 18 years and over were included in the study. Sociodemographic data were collected from the patients with a data form. Laboratory data were obtained from hospital records retrospectively. The patients were asked to respond to the BDI and SF-36 content in which depression was questioned and quality of life was evaluated respectively. The relationship between each parameter was examined. Results: 70,3 % of the patients had minimal-mild and 11,1 % of the patients had severe depression. Depression levels were significantly higher in patients who had a regular job and who had poor compliance to chelation therapy. Physical function and physical role subscales of single patients were significantly higher than married patients. Patients with monthly income had higher quality of life in terms of physical role, mental health, social functioning and pain subscales. The patients without co-morbidity had higher quality of life in terms of physical role, pain and general health subscales. Patients with severe depression had the worst quality of life. The general health perception of patients with minimal depression was higher than those with moderate depression and severe depression. Conclusions: Psychosocial support of patients is important and, therapy should be aimed not only to ensure long life without complications but also improve the quality of life of the patients.

Depression, Anxiety, and Stress Symptoms in Patients With Beta Thalassemia Major in Almadinah Almunawwarah, Saudi Arabia.

IntroductionBeta thalassemia major (BTM) is a chronic hereditary blood disorder. Patients are dependent on blood transfusion and are prone to multiple comorbidities. Depression, anxiety, and stress (DAS) can complicate their condition. No reports from Saudi Arabia to measure DAS in BTM patients. We report the prevalence of DAS symptoms in our BTM patients using the DASS-21 (Depression, Anxiety, and Stress Scale - 21 Items) test.MethodsA cross-sectional study including adolescents and adults aged 14 years and above with BTM treated in Almadinah Almunawwarah and excluding patients who had bone marrow transplant or with central nervous system insults were performed.ResultsA total of 31 male and 31 female patients were enrolled, with a mean age of 24.32 ± 7.05 years. Depression symptoms were detected in 60 % of patients, anxiety symptoms were detected in half of the studied group, and stress symptoms were detected in 38.7% of patients. We found a significant positive correlation between DAS and DASS total score. Age below or above 18, parent’s employment, patient’s educational level, and status of satisfaction about medical care were statistically significant in having positive effects on scores of DAS symptoms. ConclusionsBTM patients are prone to develop psychological disorders, which can affect the course of the disease. Our results are comparable to international and Arab population studies, which have the highest reported prevalence. It is important to not ignore the psychological evaluation of patients with BTM and to refer them for proper evaluation and management.

Increased prevalence of fractures in inadequately transfused and chelated Indian children and young adults with beta thalassemia major.

In patients with beta thalassemia major, inadequate transfusion and chelation may compromise bone health and increase risk of fractures. The objective of this study was to describe the prevalence of fractures in Indian inadequately transfused and chelated children, adolescents and young adults with beta thalassemia major. We studied 179 patients with beta thalassemia (3.6-28.3years; 105 boys). Medical, transfusion, chelation and fracture history were recorded. Vertebral fracture assessment (VFA) was performed using lateral spine images acquired using the GE Lunar iDXA (Wisconsin, MD). Fractures were classified according to an adapted semi-quantitative method. History of non-traumatic long bone fractures was observed in 21% patients (n=37); there were significantly greater (p<0.05) number of males (n=30) than females (n=15). The 21% fracture prevalence in the present study is higher than the reported fractures of 9% in healthy Indian children and adolescents. The prevalence of vertebral fractures was 4.5% (n=8) in the study group. Of those with fractures, four patients had both long bone and vertebral fractures, and (any, long bone or vertebral fractures) sixteen patients had more than 1 fracture; eleven patients had 2 fractures, four patients had 3 fractures and one patient had 5 fractures. Thus, in 179 patients, there were a total of 68 single fractures which translates to 307 fractures per 10,000 patient years. This study found increased prevalence of non-traumatic long bone and vertebral fractures in children and adolescents with thalassemia major.

SEVERE LIVER IRON CONCENTRATIONS (LIC) IN 24 PATIENTS WITH Β-THALASSEMIA MAJOR: CORRELATIONS WITH SERUM FERRITIN, LIVER ENZYMES AND ENDOCRINE COMPLICATIONS

IntroductionChronic blood transfusion is the mainstay of care for individuals with β-thalassemia major (BTM). However, it causes iron-overload that requires monitoring and management by long-term iron chelation therapy to prevent endocrinopathies and cardiomyopathies, which can be fatal. Hepatic R2 MRI method (FerriScan®) has been validated as the gold standard for evaluation and monitoring liver iron concentration (LIC) that reflects the total body iron-overload. Although adequate oral iron chelation therapy (OIC) is promising for the treatment of transfusional iron-overload, some patients are less compliant with it, and others suffer from long-term effects of iron overload.ObjectiveThe aim of our study was to evaluate the prevalence of endocrinopathies and liver dysfunction, in relation to LIC and serum ferritin level, in a selected group of adolescents and young adult BTM patients with severe hepatic iron overload (LIC from 15 to 43 mg Fe/g dry weight).Patients and MethodsTwenty-four selected BTM patients with severe LIC, due to transfusion-related iron-overload, followed at the Haematology Section, National Centre for Cancer Care and Research, Hamad Medical Corporation of Doha (Qatar), from April 2015 to July 2017, were retrospectively evaluated. The prevalence of short stature, hypogonadism, hypothyroidism, hypoparathyroidism, impaired fasting glucose (IFG), diabetes, and adrenal insufficiency was defined and assessed according to the International Network of Clinicians for Endocrinopathies in Thalassemia (ICET) and American Diabetes Association criteria.ResultsPatients’ most common transfusion frequency was every three weeks (70.8%). At the time of LIC measurements, their median age was 21.5 years with a mean age of 21.7 ± 8.0 years. Mean LIC was 32.05 ± 10.53 mg Fe/g dry weight (range: 15 to 43 mg Fe/g dry weight), and mean serum ferritin level was 4,488.6 ± 2,779 μg/L. LIC was correlated significantly with serum ferritin levels (r = 0.512; p = 0.011). The overall prevalence of short stature was 26.1% (6/23), IFG was 16.7% (4/24), sub-clinical hypothyroidism was 14.3% (3/21), hypogonadotropic hypogonadism was 14.3% (2/14), diabetes mellitus was 12.5% (3/24), and biochemical adrenal insufficiency was 6.7% (1/15). The prevalence of hepatitis C positivity was 20.8% (5/24). No case of clinical hypothyroidism, adrenal insufficiency or hypoparathyroidism was detected in this cohort of patients. The prevalence of IFG impaired fasting glucose was significantly higher in BTM patients with very high LIC (>30 mg Fe/g dry liver) versus those with lower LIC (p = 0.044). The prevalence of endocrinopathies was not significantly different between the two groups of patients with LIC above and below 15 mg Fe/g dry weight.ConclusionsA significant number of BTM patients, with high LIC and endocrine disorders, still exist despite the recent developments of new oral iron chelating agents. Therefore, physicians’ strategies shall optimize early identification of those patients to optimise their chelation therapy and to avoid iron-induced organ damage. We believe that further studies are needed to evaluate if serial measurements of quantitative LIC may predict the risk for endocrine complications. Until these data are available, we recommend a close monitoring of endocrine and other complications, according to the international guidelines.

Analysis of Skin, Hair and Nail Diseases in the Adults with Beta Thalassemia Major

Objective: β-thalassemia major (BTM) is a genetic disorder necessitating frequent blood transfusions, which is characterized by functional and physiological disorders in multiple organs. We aimed to research the prevalence of associated skin, hair, and nail disorders, and their relationship with clinical and laboratory features of the disease in adult BTM patients and healthy control groups. Materials and Methods: We prospectively analyzed the prevalence of associated skin, hair, and nail disorders. We recorded demographic features, laboratory findings skin, hair, and nail disorders in the participants. Results: Atotal of 71 BTM patients (36 males and 35 females) and 50 age and sex matched healthy individuals (36 females and 36 males) were included in the study. 32 (45.1%) of the patients and 3 (4.2%) of the control groups had hair, 26 (36.6%) of the patients and 6 (8.3%) of control groups had nail diseases. The most common skin findings xerosis were determined in 66 (93%), hair findings, telogen effluvium were determined in 16 (22.5%), and nail findings, dystrophic nail were determined 9 (12.7%) in patients. BTM patients had significantly higher fruquent xerosis, scar, pigmentation disorders, nevus, pruritus, infections, nail and hair disorders than control groups. Average age of patients with pruritus and nevus were significantly enhanced. Postinflammatory hyperpigmentation and melanocytic nevus in male patients had more higher than female patients. Telogen effluvium in female patients was more higher than male patients. Ferritin levels of the patients with ephelide, diffuse bronze pigmentation (DBP) and telogen effluim had significantly enhanced. Conclusion: Age, gender, medication history and ferritin level are important factors for the development of dermatological disorders among BTM patients.

Assessment of Growth parameters in Transfusion dependent Thalassemics at a tertiary care hospital

Background: Thalassemia is a group of genetic blood disorders all of which involve under production of haemoglobin , and partial or complete failure of synthesis a specific type of globin chain . Thalassemia major is most common monogenic disorder in the world. Around 1,00,000 children are born each year with the severe homozygous state of the disease in India. The objectives of this study was to assess clinical data and the growth parameters of thalassemia major patients attending tertiary care hospital.Beta Thalassemia Major (BTM) is transfusion dependent state where physical growth is affected in majority of patients. This study will emphasize to assess iron overload and growth parameters of transfusion dependent BTM patients. This was undertaken as very few studies have been done in this region of the our country.Methods: The study was done at a tertiary care teaching hospital from January 2014 to December 2014. Universal sampling method was used and 31 β thalassemia major patients who received blood transfusions at 2 to 4 weeks interval in the hospital were included in this study. Clinical details and blood transfusion record was collected on proforma for all patients and data interpreted. This study was done on 31 known diagnosed BTM patients with age 10 years and above. Height, weight, BMI along with hemoglobin and serum ferritin were estimated. IAP growth charts were plotted for various parameters. Appropriate statistical tests were used for analysis.Result: Of 31 patients, 25 were males and 6 were females . Age range was 10 -18 years with mean age of 12.45 years. There were 20(64.5%) patients not taking chelation. Mean and SD of pretransfusion hemoglobin of all patients was 6.85±1.13 gm%. Mean and SD of ferritin of all patients, nonchelated and chelated patients was 3786 ±2382 ng/ml, 4505±2633 ng/ml and 2479 ± 963.6 ng/ml respectively. Weight for Age (W/A) charts of males and females showed 28% and 16.6 % respectively below 3rd percentile. Height for age (H/A) charts of males showed 40 % below 3rd percentile and none of the females below 3rd percentile. BMI of males and females showed 20% and 50% respectively below 3rd percentile. Most of the patients were of short stature and underweight indicating growth failure. Conclusion: The present study describes the growth parameters of β thalassemia major patients attending the tertiary care hospital and emphasizes on maintenance of growth charts of these patients for better management. Growth failure in BTM is mainly due to iron overload and chronic anemia. This study emphasizes the need of screening for growth failure, regularly estimating iron overload and its control by chelation therapy.DOI:10.21276/APALM.1833

Assessment of left ventricular functions and myocardial iron load with tissue Doppler and speckle tracking echocardiography and T2* MRI in patients with β-thalassemia major.

The purpose of this study is to determine early myocardial dysfunction in β-thalassemia major (BTM) patients. Where the myocardial dysfunction cannot be detected by conventional echocardiography, it could be detected by tissue Doppler imaging (TDI) or speckle tracking echocardiography (STE). In this study, we analyzed 60 individuals, 30 of whom were BTM patients and the other 30 of whom were the control group. T2* magnetic resonance imaging (MRI) was used to measure cardiac iron deposition. The myocardial functions were evaluated by conventional echocardiography, TDI and STE. When basal lateral left ventricular and basal septal wall TDI values were compared between the patient group and control group, only isovolumic contraction time values were significantly longer in the patients. The global circumferential strain was significantly lower in the patients. When evaluated as segmental, longitudinal strain values of basal inferoseptum and circumferential strain values of anteroseptum, anterior, and inferolateral segments were significantly lower in the patients. In the patients, global longitudinal and circumferential strains in the group who had pathological T2* values were significantly lower than the group who did not. In addition, circumferential strain values in anteroseptum, anterolateral, inferior, and inferoseptum segments were significantly lower in the patients with T2* values<20ms than those with T2* values≥20ms. Although T2* MRI is the most sensitive test detecting myocardial iron load, TDI and STE can be used for screening myocardial dysfunction. The abnormal strain values, especially circumferential, may be detected as the first finding of abnormal iron load and related to T2* values.

Progression of Liver Fibrosis Can be Controlled Under Adequate Chelation in Transfusion-Dependent Thalassemia (TDT).

BACKGROUND. A substantial proportion of patients with transfusion-dependent beta-thalassemia major suffer from chronic liver disease. Iron overload resulting from repeated transfusions and HCV infection have been implicated in the development of liver fibrosis. The objective of iron chelation is to avoid the complications of siderosis, such as hepatocellular injury. As a matter of fact, adequate chelation therapy is mandatory in order to prevent liver disease progression. In the last few years the availability of different chelating agents (coupled with anti-HCV therapy) allowed control of liver disease due to secondary iron overload. Transient elastography (TE, Fibroscan®) is a non-invasive and rapid diagnostic tool that enables accurate prediction of hepatic fibrosis by measuring liver stiffness (LSM). Patients with TDT could benefit from regular non-invasive assessment of liver fibrosis as an indirect indicator of treatment adequacy and therapeutic compliance.AIM. We investigated the efficacy of adequate iron chelation to prevent the progression of liver fibrosis in TDT patients over a time period of approximately 4 years.MATERIALS AND METHODS. We analysed data in a retrospective cohort study over a 4±1.5-year time period. Ninety-nine patients with beta-thalassemia major (41 M, 58 F, aged 36±6 years), followed at Rare Disease Center, Ca’ Granda Hospital in Milan, were enrolled in the study. All patients received regular transfusions every 2-4 weeks. Chelation therapy was registered using deferasirox (DFX), deferoxamine (DFO), deferiprone (DFP) or a combination of the three. All the participants underwent TE and T2-weighted magnetic resonance imaging (T2*MRI) twice (at baseline,T0 and after approximately 4 years, T1). Liver iron concentration (LIC) was assessed by T2*MRI using the appropriate formula at T0 and T1. LSM was measured according to the following cut-off: <5.0 kPa no fibrosis (F0), 5.1-7.9 kPa mild fibrosis (F1), >7.9 kPa moderate fibrosis (F2), >10.3 advanced fibrosis (F3), >11.9 kPa cirrhosis (F4). We divided our cohort into groups depending on the administered chelating agent and the presence of iron overload defined by a LIC > 4.23 mg Fe/g dry weight (corresponding to a T2* value > 6.3 ms).RESULTS. At baseline the mean pre-transfusion Hb levels was 9.74 ± 1.17 g/dL, the mean iron intake 0.33 ± 0.07 mg Fe/kg/d and median serum ferritin 669.5 ng/ml (range 113-5912). HCV-RNA positivity was found in 33 patients (33%) at T0: 20 patients were treated for hepatitis C during the observation period. The overall mean LSM was 7.4±3.2 kPa, the mean hepatic T2* was 9.92±7.01 ms and the mean LIC was 4.81±3.82 mg/g dw (n=99). Data available at 4±1.5 years showed a significant reduction in liver stiffness (6.6±3.2 kPa, p 0.017), iron overload measured by hepatic T2* (12.84±7.28 ms, p < 0.001) and LIC (3.65±3.45 mg/g dw, p 0.001). This result was confirmed when considering patients with iron overload at the time of the first measurment (n=41). The number of patients with moderate to advanced fibrosis (LSM ≥ F2) decreased, yet not significantly (30% vs 19%, p 0.07). Subjects treated with a stable dose of DFX over the entire period of observation (n=39) showed a reduction of LSM (6.9±2.3 vs 6.06±2.4, p 0.04) and a concomitant improvement of hepatic T2* and LIC values (respectively 11.02±6.57 vs 15.04±6.42 and 3.84±2.81 vs 2.49±1.89, p < 0.001). In this group we observed a substantial decrease in the number of patients with LIC > 4.23 mg Fe/g dw (33% vs 13%, p 0.01). A reduction of LSM, yet not statistically significant due to the limited size of the cohort, was achieved in patients on combined DFO+DFP at T0 and T1 (n=6, 8.6±5.5 vs 7.3±3.8). The group of patients on DFO (n=11) remained stable over time. Patients who underwent anti-HCV therapy showed an even more evident reduction in LSM (9±3 vs 7±3.1, p 0.016).CONCLUSION. These data support evidence on the efficacy of adequate iron chelation therapy and, if necessary, anti-HCV treatment in decreasing or at least controlling the progression of liver fibrosis measured by TE in transfusion-dependent BTM patients. Therapeutic compliance and tailoring of drugs is essential to prevent hepatic injury resulting from siderosis. Moreover, proper chelation and treatment of HCV infection act sinergistically to limit progression of liver disease in TDT patients with active hepatitis C, so that development of cirrhosis could be either prevented or greatly delayed. DisclosuresCappellini:Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genzyme-Sanofi: Membership on an entity's Board of Directors or advisory committees.

Prevalence of Endocrinopathies in Turkish Children With β-Thalassemia Major: A Single-Center Study.

Present chelation protocols have increased the life quality and survival of the patients with β-thalassemia major (BTM). However, endocrine complications are still mostly experienced. The aim of this study was to determine the prevalence of endocrine complications in children with BTM, and to study the relationship between serum ferritin levels and complications. Forty-five children (female: 23/male: 22, mean age: 12.39±3.72 y) with BTM were enrolled into the study. Blood samples were taken after an overnight fasting, early in the morning from entire study group. Median (range) serum ferritin of the patients was 1365 ng/mL (362 to 5996 ng/mL). The most prevalent endocrine complications were vitamin D insufficiency (54.5%), short stature (42%), pubertal impairment (25% for each sex), and osteopenia (13%), respectively. Ferritin levels were not correlated with anthropometric or laboratory data. Monitoring of growth, vitamin D status, and endocrine functions are essential to achieve a good quality of life in BTM patients.

Donor Lymphocyte Infusion in Patients with Thalassemia Major Who Have Mixed Chimerism Following Allogeneic Stem Cell Transplant

▪Allogeneic stem cell transplantation (HSCT) is the only curative option for patients with thalassemia major (BTM). HSCT in BTM is associated with increased risk of graft rejection. Some patients do not achieve full donor chimerism after transplant despite hematopoietic engraftment. Early post transplant mixed chimerism (MC) is a known predictor of secondary graft rejection. Data is limited on the role of donor lymphocyte infusion (DLI) to prevent secondary graft rejection following detection of early MC in BTM. We report our experience with DLI in BTM patients who had developed progressive worsening early MC after HSCT.All patients with BTM who underwent HSCT at our centre between September 1994 and December 2013 were included in the analysis. During this period, 406 patients underwent HSCT for BTM. Median age was 8 years (range: 1 - 25) and 247 were males (60.8 %). Conditioning regimen was busulphan based in 274 (67.5%) or treosulfan based in 132 (32.5%). The graft source was BM in 305 (75.1%) and PBSC in 101 (24.9%) etc. Median CD34 stem cell dose was 9.24x106/kg (range: 2.1- 33). GVHD prophylaxis consisted of CSA and short course MTX.Patients who engrafted underwent chimerism analysis of peripheral blood at day 28 and between days 60-90. Subsequently chimerism analysis was done at the discretion of the treating physician. Chimerism analysis was done by qualitative and quantitative methods up to 2007 and by quantitative method from 2007.MC was defined by >5% recipient cells at any time point post transplant. The severity of MC was determined as per previously published criteria (level I= < 10%, level II = 10-25 %, level III = >25 %). In patients who developed MC, immunosuppression was tapered and stopped and chimerism monitored. Cyclosporine was tapered by approximately 30% every 2 weeks until there was stable MC or complete donor chimerism. If progressive loss of donor chimerism leading to level II or III MC occured on two consecutive occasions with a concurrent drop in hemoglobin despite stopping immunosuppression and in the absence of GVHD, DLI was given. Patients should have had at least 10% donor chimerism in order to have a DLI.There were 109 (41.6 %, out of 262 patients in whom chimerism was done) patients who developed MC. Of these, 35 (32.1%) developed progressively worsening MC and drop in hemoglobin despite tapering of immunosuppression (91% of these were within day 60). Of these 35 patients, 23 (65.7%) received DLI while 12 developed anemia requiring transfusion (4continued to be on blood transfusion and 8 underwent a second transplant).Among 23 patients who received DLI, 9 (39.1%) showed response (rise in Hb with CC or stable MC) while 14 (60.9%) failed to show any response. The median time to show response was 28 (8-192) days and the median time to peak response was 44 (23-442) days. The 14 patients who did not show any response developed anemia requiring transfusion (11 continued to be on blood transfusion while 3 underwent a second transplant). While 80% of those with level II chimerism responded to DLI, only 31.2% of those with level III chimerism showed a response (summarized in Table 1).DLI was well tolerated by the majority of the patients. However, 7 (30.4%) patients developed cytopenia. While 6 of these had level III chimerism at the time of DLI, 1 had level II chimerism. Two patients developed Grade IV cytopenia. Grade 2 acute GVHD developed in 3 (13%; liver=2, gut=1) which responded to immunosuppressive treatment. Chronic GVHD developed in 2 (8.7%: extensive=1). There was no mortality related to DLI.DLI helped close to 40% patients achieve either complete donor chimerism or stable MC who otherwise might have required a second stem cell transplant with minimal risk. There was a trend to suggest that early administration of DLI at level II MC was superior to DLI administered at level III.Table 1Factors affecting the response to DLIn(%)Effect of DLIResponse(CC+Stable MC)No responsepChimerism levelI 000II 54(80%)1III 165(31.2%)110.07MC 202Lucarelli classI 11(100%)0II 83(37.5%)5III 145(35.7% )90.4ConditioningBu-Cy-ATG/ALG 124(33.3%)8Thio-Treo-Flu 115(45.5%)60.7GraftBM 175(29.4%)12PB 64(66.7%)20.1Time of 1st DLI<180 days 187(38.9%)11>180 days 52(40%)31.0Total239(39.1%)14 DisclosuresNo relevant conflicts of interest to declare.

Leukocytes apoptosis and adipocytokines in children with beta thalassemia major.

β-Thalassemia is a significant public health problem in Egypt. Infectious complications represent the second most common cause of mortality and the major cause of morbidity in β-thalassemia major (BTM). The increased susceptibility of these patients to infectious diseases has been attributed to the abnormalities of the immune system, which is evident by systemic inflammation and immune deficiency. In a case control study, 35 patients with BTM were compared with 30 sex- and age-matched children who served as controls. Serum ferritin, high-sensitive CRP (hsCRP), leptin and adiponectin levels were determined in all subjects. Apoptosis of neutrophils and lymphocytes was measured by the Annexin V-fluoroisothiocyanate binding assay. Serum leptin was significantly lower in patients when compared to controls. In contrast, adiponectin and hsCRP levels were significantly higher in the patients than the controls. Positive correlation was found between adiponectin and hsCRP. BTM patients had significantly higher total leukocytes, neutrophils and lymphocytes compared with controls. BTM children exhibited a significantly increased apoptosis in T-lymphocytes; however, there was no significant difference in the percentage of apoptosis of B-lymphocytes and neutrophils between the patients and the controls. There was a significant negative correlation between serum leptin and the percentage of apoptotic T-lymphocytes. Our BTM patients had a high percentage of apoptotic T-lymphocyte in comparison with controls. In addition, they had disturbed serum levels of adipocytokines and inflammatory markers. These derangements could have a role in the immunological disturbance observed in thalassemic patients.

Effects of micro environmental factors on natural killer activity (NK) of Beta Thalassemia major patients

The physiological mechanisms of decreased NK activity of β-Thalassemia major (BTM) patients are unknown. To assess in vitro effects of mononuclear cells and their cytokine secretion on NK activity, we compared activator receptor levels and cytotoxic activity of purified NK cells and NK cells in mononuclear cells (MNC) pools. We collected cell supernatant from unincubated and incubated MNC with K562 cells and measured their secreted cytokines levels. CD16 was lower on the surface of NK cells in MNC pools from BTM patients compared to healthy volunteers. This inhibition does not appear when NK cells were purified. NKp30 levels in NK cells decreased both as purified cells and as part of a pool of MNC in BTM patients. After incubation of MNC pools with K562 target cells, we found that supernatant levels of IL10, TGFβ1 and IL15 cytokines were also significantly higher in BTM patients compared to healthy volunteers.

Assessment of the uvulo-glossopharyngeal dimensions in patients with β-thalassemia major

Thalassemia patients present varying degrees of craniofacial characteristics, while the morphology of the upper airway is less studied. The purpose of this study was to compare the uvula-glossopharyngeal dimensions (UGDs) of patients with β-thalassemia major (BTM) with non-thalassemic subjects who had similarities in the maxillo-mandibular skeletal pattern. The material for this cross-sectional retrospective study consisted of lateral cephalograms of 40 BTM patients (23 males, 17 females, aged 9.5 ± 0.97 years). These were compared with lateral cephalograms of a control group of 40 non-thalassemic subjects (23 males, 17 females, aged 11.0 ± 0.87 years). The control group was chosen so that they had similarities with the BTM patients in the following cephalometric variables: SNA (in degree), SNB (in degree), ANB (in degree), and anterior facial height (N-Me). The following UGDs in thalassemic subjects were significantly shorter in patients with BTM: tongue length (P < 0.05), the distance between the hyoid bone and the mandibular plane (P < 0.01), and the vertical distance between hyoid bone and the C3-RGN line (line connecting third vertebra and retrognathion) (P < 0.05). The middle airway space in BTM patients was significantly wider (P < 0.05), and a trend was observed for the wider inferior airway space (P = 0.07). Based on this study, some UGDs in BTM patients were significantly different, compared to non-thalassemic subjects who had a similar maxillo-mandibular skeletal pattern. These findings may have implications for the long-term treatment of BTM patients; however, since groups were not exactly age-matched, the observed differences between groups could be attributed to either BTM, age, or both. Additional studies with age-matched subjects are needed to investigate the relationship between BTM and UGDs.