Adult Thalassemia Major Patients Research Articles

Bone Mineral Density, Serum Calcium, and Vitamin D Levels in Adult Thalassemia Major Patients: Experience From a Single Center in Eastern India

Background and objectivePatients suffering from thalassemia major are at higher risk of osteoporosis. Due to their decreased life expectancy, the number of adult patients is low. However, their bone health is rarely checked in developing countries like India. There is no data available in the literature on the bone mineral density (BMD) of adult (aged ≥18 years) thalassemia major patients in eastern India. In this study, we aimed to measure the BMD and serum calcium and vitamin D levels in adult thalassemia major patients and to compare them with healthy controls.Materials and methodsWe conducted this cross-sectional observational study at a tertiary care hospital in eastern India. We recruited adult thalassemia major patients who were not on calcium or vitamin D supplements. Their BMD was measured by dual-energy X-ray absorptiometry (DXA) on the lumbar spine (L1-L4). Venous blood was tested for serum calcium and vitamin D levels. We compared the parameters between the cases and controls by using the Mann-Whitney U test.ResultsA total of 31 (male = 19, female = 12) patients with a median age of 28 years comprised the case group. Age- and sex-matched controls showed similar height but higher weight and BMI. The serum calcium level was similar (p = 0.43) in the case and control groups but T-score (p = 0.0003) and vitamin D levels (p: <0.0001) were significantly lower in thalassemia major patients.ConclusionBased on our findings, adult thalassemia major patients have lower BMD and vitamin D levels. Although the serum calcium may be normal in these patients, they should still be screened both for BMD and vitamin D for prompt and early detection of risks and complications so that a proper management strategy can be implemented.

Quantification of pancreatic iron overload and fat infiltration and their correlation with glucose disturbance in pediatric thalassemia major patients.

Diabetes mellitus affects more than a quarter of patients with thalassemia major (TM) worldwide, and increases the risk for cardiac complications, contributing to significant morbidity. Pancreatic iron overload (IO) and fat infiltration have been correlated with this endocrinal complication in adult TM patients. It has been shown that in adult TM patients, iron accumulation and fat infiltration are found to be heterogeneous in the pancreatic head, body, and tail region. R2* and a fat fraction (FF) generated by gradient-echo imaging can be used as quantitative parameters to assess the iron and fat contents of the pancreas. This study aimed to determine the pattern of pancreatic iron accumulation and fat infiltration in pediatric TM patients with gradient-echo imaging and evaluate the association between pancreatic IO and fat infiltration and glucose disturbances. A total of 90 children with TM (10.7±3.1 years) were included. All patients underwent pancreatic magnetic resonance imaging (MRI) using multi-echo gradient-echo sequences. IO was measured by R2* relaxometry in 90 patients, and FF values were measured using iterative decomposition of water and fat with echo asymmetry and the least-squares estimation (IDEAL) method in 40 patients. R2* and FF were assessed in the pancreatic head, body, and tail. The global R2* and global FF values were obtained by averaging the respective values from the pancreatic head, body, and tail. The correlations between global R2*, global FF, and fasting glucose were determined using Spearman's correlation analysis. The Friedman test was used to compare R2* and FF among different pancreatic regions. Receiver operating characteristic (ROC) analysis was used to determine the performance of global R2* and global FF in discriminating impaired fasting glucose from normal fasting glucose patients. The global R2* was positively correlated with the global FF in the pancreas (r=0.895, P<0.001). No significant differences were found in R2* among the 3 regions of the pancreas (χ2=4.050, P=0.132), but significant differences were found in FF among the 3 pancreatic regions (χ2=16.350, P<0.001). Both global pancreatic R2* (r=0.408, P<0.001) and global FF (r=0.523, P=0.001) were positively correlated with fasting glucose. ROC analysis showed that global pancreatic R2* and global FF had an area under the curve of 0.769 and 0.931 (both P<0.001), respectively, in discriminating between impaired and normal glucose function patients. Pediatric TM patients can have homogeneous iron siderosis and heterogeneous fat infiltration in the pancreas as measured by gradient-echo imaging, both of which are risk factors for diabetes.

Iron Overload Associated Endocrine Dysfunction Leading to Lower Bone Mineral Density in Thalassemia Major.

Patients with thalassemia major (TM) have a lower bone mineral density (BMD) and higher risk of fracture than the general population. The possible mechanisms include anemia, iron overload, malnutrition, and hormonal deficiency, but these have not been thoroughly investigated. To identify major mineral and hormonal factors related to BMD in adult TM patients to provide human evidence for the proposed mechanisms. Retrospective study. Referral center. Twenty-nine patients with β-TM, aged 23 to 44 years who were followed-up during 2017 to 2018 were enrolled. Endocrine profiles, including thyroid, parathyroid, and pituitary function, glucose, vitamin D, calcium, phosphate, and fibroblast growth factor 23 (FGF23) were obtained. The relationships among the above parameters, body height, fractures, and BMD were analyzed. Abnormal BMD was observed in 42.9% of women and 23.1% of men. The mean final heights of women and men were 3.7 cm and 7.3 cm lower than the mean expected values, respectively. Fracture history was recorded in 26.7% of women and 35.7% of men. BMD was negatively correlated with parathyroid hormone, FGF23, thyrotropin, and glycated hemoglobin (HbA1c) levels, and positively correlated with testosterone, IGF-1, and corticotropin levels (all P < .05). Moreover, hypothyroidism was associated with lower BMD in both the lumbar spine (P = .024) and the femoral neck (P = .004). Patients with hypothyroidism had a higher percentage of abnormal BMD (P = .016). Hypothyroidism, higher HbA1c, and lower adrenocorticotropin were predictors of abnormal BMD in patients with β-TM. Whether the correction of these factors improves BMD warrants further research.

Endocrine profile of β-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center.

Aim:Chronic iron overload resulting from frequent transfusions, poor compliance to efficient chelation therapy and chronic liver disease is basically responsible for the most severe complications of thalassemia major (TM). Before conventional treatment, TM was entirely childhood disease with a very short survival. Today, survival improved to 40–50 years and becomes a prevalent disease of adulthood and in the near future it will be one of senility. Furthermore, clinical phenotype of TM is changing with age and appearance of severe complications from the heart and endocrine glands that require special health care from well-informed specialists.Objectives:The aims of our study were to: (1) Imprint the clinical profile of long-lived TM patients; (2) evaluate retrospectively the cumulative incidence of endocrine diseases; (3) identify potential risk factors; and (4) orient the physicians in the modified clinical phenotype and the relative patients' health needs.Design:A retrospective cross-sectional study followed from childhood to adulthood by the same physician in a tertiary thalassemia clinic.Participants:Forty-three long-lived TM patients (mean age: 50.3 ± 10.8 years; range: 45.8–59.5 years; 23 females) were studied.Patients and Methods:An extensive medical history, with detailed clinical and laboratory data, endocrine complications, and current treatments, was obtained.Results:The data indicate that 88.4% of adult TM patients suffered from at least one endocrine complication. The majority of patients developed endocrine complications in the second decade of life when serum ferritin level was very high (12/23 TM female and 8/20 TM male patients, the serum ferritin levels at the diagnosis were above 5.000 ng/ml).Conclusions:These data underline that endocrine and bone complications in adult TM patients are highly prevalent and necessitate close monitoring, treatment, and follow-up. Physicians' strategies to optimize chelation therapy include identifying patients who are at risk for developing organ damage, developing chelation plans, promoting compliance, and educating patients. Several clinical aspects remain to be elucidated such as growth and impairment of glucose tolerance in relation to hepatitis C virus infection. Furthermore, affordable worldwide-established long-term treatment protocols for hypogonadism and osteoporosis are needed.

Cardiac Iron Overload Assessed by T2* Magnetic Resonance (CMR) In Thalassemia Major Patients Treated with Different Iron Chelators

AbstractAbstract 4275 Introduction.Although iron chelation therapy has markedly improved the survival, heart failure due to myocardial iron overload still remains the leading cause of morbidity and mortality in adult thalassemia major (TM) patients. T2* cardiovascular magnetic resonance (CMR) is a non invasive technique that provides rapid and direct assessment of myocardial iron content and its usefulness in monitoring iron chelation has been proved (Wood et al, Circulation 2009). AIM OF THE STUDY. To evaluate the efficacy of different iron-chelation therapies on removal of cardiac iron content assessed by CMR in adult TM patients. PATIENTS AND METHODS. Sixty-seven TM patients (27 males/40 women, mean age 35 ± 6 yrs) treated with different iron chelators underwent repeated cardiac CMR to assess myocardial iron load. Myocardial T2* was assessed at baseline (t0), after 6–14 months (t1) (according to clinical conditions and to T2* at baseline), and as second control (t2) after a mean of 32±7 months from baseline. CMR was performed at Cardiology and CMR Department “A. De Gasperis” at Niguarda Ca' Granda Hospital in Milan, using a 1.5 Tesla MR scanner (Avanto Siemens, Erlangen). Normal cardiac T2* was defined > 20 ms; T2* < 10 ms indicated severe cardiac siderosis and T2* between 10 and 20 ms moderate-to-mild cardiac siderosis. Each patient has to be chelated with the same iron chelation therapy at least for 1 year before the baseline CMR evaluation. Patients were divided based on chelation therapy in 4 groups: group A (n=36, 53.7 %) patients chelated with deferasirox (DFX, mean actual dose 27±7 mg/Kg/die), group B (n=15, 22.4 %) deferoxamine (DFO, actual mean dose 48±9 mg/kg for a median of 6 days/week), group C (n=12, 17,9 %) DFO (mean actual dose 46±7 mg/kg for a median of 4 days/week) plus deferiprone (DFP, mean actual dose 73±7 mg/kg/day) and group D (n=4,6 %) only DFP (mean actual dose 75±0 mg/kg/day). Statistical analysis was performed using a paired Student's t-test. RESULTS. Overall, the pre-transfusional mean hemoglobin (Hb) was 9.7±0.5 g/dl, the median ferritin value was 913 ng/ml (range 229–5934 ng/ml) and the mean iron intake was 0.41±0.12 mg/Kg/day. In the overall population, the baseline myocardial T2* was < 10 ms in 8 patients (11.9 %), between 10 and 20 ms in 22 patients (32.8 %) and ≥ 20 ms in 37 patients (55.2 %). At baseline evaluation, T2* < 10 ms was detected only in 1 patient (1/36: 2.77 %) in group A, in 4 patients (4/15: 26.6 %) in group B and in 3 patients (3/12: 25 %) in group C. In group D all patients showed a myocardial T2* above 20 ms at baseline. Progressive changes in T2* values were observed at t1 and t2 for all the groups. Ten patients (10/36: 27.8 %) in group A, 3 patients (3/15: 20 %) in group B, 3 patients (3/12: 25%) in group C, respectively, moved from an abnormal T2* (< 20 ms) to normal values, in 32±7 months (Table 1). T2* values at t2 improved significantly compared to baseline (p=0.0006) in patients treated with DFX (group A). In patients treated with combination therapy (DFO and DFP), T2* increased more rapidly in those with severe siderosis (T2* < 10 ms) (p=0.006). No significant changes in left ventricular ejection fraction (LVEF) values were observed in all groups of patients: only patients in group A with baseline cardiac T2* between 10 and 20 ms showed a slight improvement in LVEF (p=0.049). No statistically significant reduction in ferritin levels were associated with ameliorating myocardial T2* values. DISCUSSION AND CONCLUSIONS. Our data showed that compliance to chelation therapy at proper doses significantly improve myocardial T2* over 3-year treatment period. Continued treatment with deferasirox significantly increase myocardial T2* over time, showing its efficacy to remove iron from the heart. DFO and DFP combination therapy seems to ameliorate cardiac T2* more rapidly only in patients with T2* < 10 ms at baseline.Table 1t0t1t2GROUP An.T2*(ms)n.T2*(ms)n.T2*(ms)T2* < 10 ms18.70–0–T2* 10–20 ms1315.3 ± 2.9125.8 ± 2.8415.8 ± 1.9T* > 20 ms2232.3 ± 6.52434.6 ± 6.83233.8 ± 8.0GROUP BT2* < 10 ms48.5 ± 1.137.2 ± 1.70–T2* 10–20 ms414.1 ± 3.8613.5 ± 3.1512.3 ± 1.5T* > 20 ms731.5 ± 7.8632.9 ± 10.01030.4 ± 9.8GROUP CT2* < 10 ms35.9 ± 1.337.9 ± 1.226.9 ± 0.6T2* 10–20 ms513.7 ± 3.0513.4 ± 1.9316.9 ± 3.3T* > 20 ms438.4 ± 17.0438.0 ± 10.7739.8 ± 6.4 Disclosures:No relevant conflicts of interest to declare.

Bone Density in Thalassemia Major Improves in Longterm Transplant Survivors.

Background: Bone-related complication is a major longterm morbidity for thalassemia major (TM), and osteoporosis significantly increases the risk of fractures. Up to 60% of adult TM patients suffer from osteoporosis. It remains unclear whether diminished bone mineral density (BMD) in TM can be reversed after bone marrow transplantation (BMT). Objective: This study investigates the effects of BMT on BMD measurement in TM patients by comparing BMD in those receiving regular blood transfusion (BT) with patients following BMT.Patients and Methods: This study recruited all Chinese TM patients managed in the pediatric department of a university teaching hospital in Hong Kong. Medical history and details on BT or BMT and drug treatments were obtained from chart review. All BMT patients were ≥ 2 years post-transplant. They did not receive any medication or suffer from any transplant-related complication for ≥ one year. Pubertal development was assessed clinically by Tanner staging, and supplemented with hormonal studies if indicated. BMD at lumbar spine (L1-L4) and left hip were measured by dual-energy x-ray absorptiometry (DEXA). Osteoporosis was defined quantitatively as T-score for BMD < -2.5. Paired blood and urine samples were collected in the mornings of DEXA scan for biochemical markers, including serum osteocalcin and bone-specific alkaline phosphatase (ALP) levels for bone formation and serum beta-crossLap and urine cross-linking deoxypyridinoline (DPD) levels for bone resorption. Student t test was used to analyze numerical values and chi-square was used to compare proportions.Results: 53 TM patients on regular BT and 33 post-BMT patients were recruited. Their mean (SD) ages were 14.4 (5.9) years and 15.6 (5.8) years (p=0.346). Patients in the latter group were 5.7 (1.9) years after BMT. Thirteen (25%) BT patients and 13 (39%) post-BMT patients suffered from endocrinopathy (p=0.144). Similar proportions of BT and BMT patients showed signs of puberty (62% versus 67%; p=0.679). The mean (SD) serum ferritin concentrations in these two groups were 7401 (3770) pmol/L and 1348 (1144) pmol/L, respectively (p<0.0001). BMD T-scores were < -2.5 at spine and hip in 62% and 35% of BT-dependent TM patients, and in 36% (p=0.063) and 6% (p=0.036) of post-BMT patients. Absolute BMD at spine in these two groups were 0.636 (0.115) g/cm2 and 0.684 (0.155) g/cm2 (p=0.102), whereas the respective values at hip were 0.651 (0.121) g/cm2 and 0.706 (0.149) g/cm2 (p=0.092). Sub-group analysis revealed that pubertal post-BMT patients had significantly higher hip BMD as compared to those on regular BT (p=0.044). Serum osteocalcin concentrations were significantly higher in BMT than BT patients (mean [SD]: 96.4 [72.7] μg/L versus 68.9 [40.3] μg/L; p=0.037). The other biochemical markers of bone turnover did not differ between the two groups of TM patients. Lastly, BMD values were not associated with the presence of endocrinopathy, extent of iron overload or dosage of desferrioxamine in BT-dependent TM patients.Conclusions: Osteoporosis is common among Chinese teenagers and young adults with TM. Our results support that BMD measurement should form an integral part of longterm follow-up in TM patients. Transplant survivors of TM had significantly better BMD at left hips as compared to those on regular BT, and this may result from increased bone formation in the post-transplant patients.