Amlodipine: Can act as an antioxidant in patients with transfusion-dependent ß-thalassemia? A double-blind, controlled, crossover trial.

BACKGROUND AND AIM: This study aimed to assess the antioxidant effects of amlodipine in transfusion-dependent ß-thalassemia (TDT) patients. METHODS: This crossover trial consisted of two sequences (AP and PA). In the AP sequence, nine cases received amlodipine 5 mg daily (phase I) and then were switched to placebo (phase II). In PA sequence, 10 patients took the placebo (phase I) and were shifted to amlodipine (phase II). The washout period was 2 weeks. The length of each phase was 6 months. Serum malondialdehyde (MDA, µmol/L), carbonyl (protein CO, µM/L), glutathione (GSH, nM/L), and total antioxidant capacity (TAC, µmol FeSO4/L) were measured in the beginning and at the end of phases I and II. The clinical significance was viewed as a minimum change difference of 5% for each outcome between amlodipine and placebo. RESULTS: Seventeen cases completed the study. According to the baseline MDA values, the adjusted Hedges's g for MDA was -0.59, 95% confidence interval [CI] -1.26 to 0.08. After controlling the baseline protein CO values, Hedges's g computed for protein CO was -0.11, 95% CI -0.76 to 0.55. The estimated values of the adjusted Hedges's g for GSH and TAC were also 0.26, 95% CI -0.40 to 0.91, and 0.42, 95% CI -0.24 to 1.09, respectively. The change difference for MDA was 8.3% (protein CO 2.2%, GSH 3.1%, and TAC 12.9%). CONCLUSION: Clinically, amlodipine therapy is an efficacious adjuvant treatment with conventional iron chelators for improving the levels of MDA and TAC in patients with TDT.

A double-blind, controlled, crossover trial of amlodipine on iron overload status in transfusion dependent ß-thalassemia patients.

BACKGROUND AND AIM: This study examined whether administration of amlodipine could improve myocardial iron loading status in patients with transfusion dependent ß-thalassemia (TDT), through a placebo-controlled, crossover study. METHODS: Amlodipine (5 mg, daily) or placebo were prescribed to all patients (n = 19) for 6 months, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of amlodipine on iron loading was assessed by measuring myocardial T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) and serum ferritin (ng/mL). RESULTS: Seventeen patients completed the study. The mean ± standard deviation [SD] of myocardial MRI T2* at baseline was 9.83 ± 2.67 ms Myocardial MRI T2* value rose to 11.44 ± 4.14 ms post amlodipine treatment in all patients. After placebo, myocardial MRI T2* value reached 10.29 ± 4.01 ms After controlling the baseline measures, Hedges's g for ferritin and myocardial MRI T2* outcomes were estimated 3.84 (95% confidence interval [CI] 2.68 to 4.97) and -1.80 (95% CI -2.58 to -0.10), respectively. CONCLUSION: Amlodipine might improve myocardial MRI T2* and serum ferritin level compared to placebo. However, larger clinical studies are needed to confirm the results.

Iron-chelating effect of silymarin in patients with ß-thalassemia major: A crossover randomised control trial.

This study aimed to determine the potential iron-chelating effects of silymarin in patients with ß-thalassemia major receiving standard iron-chelation therapy. We evaluated whether addition of silymarin to standard iron-chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo-controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron-binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron-binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron-chelation and silymarin therapy was effective for improving the iron-burden status in patients with ß-thalassemia major.

Correlation of Pancreatic Iron Overload Measured by T2*-Weighted Magnetic Resonance Imaging in Diabetic Patients with ß-Thalassemia Major.

Diabetes mellitus (DM) is one of the potential complications in patients with transfusion-dependent ß-thalassemia major (ß-TM). In this case-controlled study, we examined the pancreatic iron levels in outpatients with ß-TM. In this study, cases of patients with ß-TM and DM were gender- and age-matched with control subjects, who were non-diabetic and had normal blood glucose on standard oral glucose tolerance (OGTT) tests. One of four diagnoses [normal, pre-diabetes, impaired glucose tolerance (IGT), DM] was made according to the American Diabetes Association (ADA) criteria. The T2*-weighted magnetic resonance imaging (T2*-weighted MRI) of the heart, liver, and pancreas was performed using a 1.5 Tesla scanner. The study enrolled 26 diabetic cases, 17 non-diabetic cases, and eight cases of IGT or pre-diabetes cases. The severity of pancreatic and cardiac iron siderosis was significantly different between the groups. We found a statistically significant difference at 5.6 ms in the T2*-weighted MRI values for the pancreas between patients with normal vs. abnormal glucose metabolism [p < 0.009; odds ratio (OR): 11.2; 95% confidence interval (95% CI): 1.32-94.4)]. The receiver operating characteristic (ROC) curve for the 5.6 ms cutoff led to an area under the curve (AUC) of 0.69 (95% CI: 55.0-84.0; p < 0.02), with sensitivity and specificity of 94.0 and 42.0%, respectively. There was a moderate positive correlation between pancreatic and cardiac T2*-weighted MRI (r = 0.4; p < 0.001), and a weak correlation between the pancreas and the liver (r = 0.38; p < 0.005). To conclude, we have introduced a cutoff of 5.6 ms on T2*-weighted MRI of the pancreas for prediction of abnormal glucose metabolism in ß-TM patients.

Non-invasive prenatal diagnosis of ß-thalassemia by detection of the cell-free fetal DNA in maternal circulation: a systematic review and meta-analysis.

The discovery of fetal DNA (f-DNA) opens the possibility of early non-invasive procedure for detection of paternally inherited mutation of beta-thalassemia. Since 2002, some studies have examined the sensitivity and specificity of this method for detection of paternally inherited mutation of thalassemia in pregnant women at risk of having affected babies. We conducted a systematic review of published articles that evaluated using this method for early detection of paternally inherited mutation in maternal plasma. A sensitive search of multiple databases was done in which nine studies met our inclusion criteria. The sensitivity and specificity was 99 and 99 %, respectively. The current study found that detection of paternally inherited mutation of thalassemia using analysis of cell-free fetal DNA is highly accurate. This method could replace conventional and invasive methods.

Marriage and child bearing in patients with transfusion-dependent thalassemia major.

AIM: With good care, patients with transfusion-dependent thalassemia major (TDTM) can reach older ages, marry and reproduce. This study was conducted by the Thalassemia Research Center. MATERIAL AND METHODS: Medical notes of all TDTM patients and all non-transfusion-dependent thalassemia major (NTDTM) patients were reviewed from July to December 2012. Also, patients were interviewed. The questionnaire was made in consultation with research methodology experts and reliability was achieved by a pilot study of 12 patients, by the test-retest method (r = 0.9). Epidemiologic characteristics of patients and the pregnancy outcomes were recorded. Descriptive statistics were used with SPSS 17. RESULTS: Four hundred and nineteen medical records were reviewed. Three hundred and forty-five (82.5%) were TDTM. One hundred and seventy-five (50.7%) were female with a mean age of 25.4 ± 7.05 years and 42 (25%) had been married. Mean age of menarche and marriage was 15.4 ± 1.6 and 21.8 ± 4.5 years, respectively. Total number of live children is nine so far. Mode of delivery in female patients was cesarean section. Almost 78% of newborns weighed 2500-4000 g. Almost 22% of pregnancies were assisted. Male patients consisted of 170 (49.3%) and 55 (32.3%) of them had been married. Mean age at marriage was 24.27 ± 3.5 years. CONCLUSIONS: With better management, patients with TDTM can reach the age of reproduction. Medical teams should be prepared for this possibility.

Why does the Iranian national program of screening newborns for G6PD enzyme deficiency miss a large number of affected infants?

PURPOSE: G6PD enzyme deficiency is one of the most prevalent genetic disorders worldwide and it has high incidence rate in Northern provinces of Iran. It was observed that national neonatal screening for G6PD enzyme deficiency fails to detect all affected infants. In order to clarify the cause, this study has been done in Thalassemia Research Center, Sari, Iran. MATERIALS AND METHODS: This was a diagnostic study. The newborns with parents of Mazandarani origin were enrolled. Cord blood from the placental side was collected and used for decolorization test, quantitative enzyme assay (QEA) and DNA study. A heel-prick sample collected on day 3-5 after birth was used for fluorescent spot test (FST). In male cases, QEA was considered as the gold standard. For females, DNA study was considered as the gold standard. Based on QEA test results, neonates with <20% and 20-60% of mean normal enzyme activity were considered as total deficient and partial deficient, respectively. RESULTS: A total of 365 neonates (52.3% females and 47.7% males) were studied. According to FST, 13 male newborns had G6PD deficiency. No deficient female was detected. Decolorization test diagnosed 18 male and one female as G6PD deficient newborns. QEA diagnosed 19 males and 28 females with G6PD enzyme deficiency (26 partial, 2 total deficient cases). DNA analysis detected 14 males as hemizygote and 34 females as heterozygote. CONCLUSION: FST does not have the required sensitivity for newborn screening and QEA is recommended as the preferred method.

Report on patients with non transfusion-dependent ß-thalassemia major being treated with hydroxyurea attending the Thalassemia Research Center, Sari, Mazandaran Province, Islamic Republic of Iran in 2013.

Hydroxyurea (HU) has been used to treat patients with non transfusion-dependent ß-thalassemia major (ß-TM) at the Thalassemia Research Center, Sari, Mazandaran Province, Islamic Republic of Iran since 1996. This study was performed to summarize and to share our experience. Medical records of all patients with ß-thalassemia (ß-thal) attending our center were reviewed in January 2013. Definition of ß-TM was based on complete blood count (CBC), hemoglobin (Hb) electrophoresis, and for some patients, by the amplification refractory mutation system-restriction fragment length polymorphism (ARMS-RFLP) method. Patients who had not been transfused before, or had only occasionally had blood transfusions, were selected. Age at first blood transfusion, initial HU therapy and time of study was extracted from the records. The lowest Hb level before using HU and the last Hb value when on the HU regimen as well as the difference, were reported. Number of saved packed red cells was calculated according to duration of HU use and the usual needs of the patients. Hydroxyurea was discontinued before a planned pregnancy and during gestation and lactation periods. Hydroxyurea was discontinued for male patients willing to reproduce. A p value of <0.05 was considered statistically significant. It was consistent with 1856 patients/year, and 3542 units of blood were saved. We found HU to be effective and safe in treating patients with non transfusion-dependent ß-TM. We strongly recommend HU therapy.

The effect and side effect of hydroxyurea therapy on patients with ß-thalassemia: a systematic review to December 2012.

Hydroxyurea (HU) is being used for patients with transfusion-dependent ß-thalassemia major (ß-TM) as well as non transfusion-dependent ß-TM. As controversy exists regarding efficacy and safety of HU, we searched the published literature on efficacy, effectiveness and toxicity of HU in patients with ß-TM. The research sources we used were: Medline, SID, PubMed, Scopus, Request, Web of Knowledge, Springer, Ovid, Cochrane searched up to October 2012. Using search terms sensitive to studies of clinical trials combined with searches on terms related to thalassemia and HU. We selected studies on randomized trials, quasi experimental trials (before and after design), case reports (with 1-5 cases), side effect studies in patients with ß-TM, studies related to the mechanism of action and toxicity when used in patients with other hemoglobinopathies. We researched studies in English and Persian. Eligible articles were reviewed by two independent reviewers. Patient's characteristics, duration of trial, outcome and side effects were extracted. The main outcomes were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic, Tau(2) and I(2). Subgroup analyses were performed and the statistics data (STATA) software used. More than 500 articles were reviewed. No randomized clinical trial was found. Seventeen trials with before and after designs were found, 16 case reports (1-5 cases), 19 articles for mechanism of action and 16 studies for side effects were published from 1969 to October 2012. Hemoglobin levels after treatment showed modest but significant increase in non transfusion-dependent ß-TM (p < 0.0001) and in transfusion-dependent ß-TM (p < 0.0001).

Two risk factors for hypozincemia in diabetic ß-thalassemia patients: Hepatitis C and deferasirox.

BACKGROUND AND AIM: Hypozincemia is a prevalent adverse consequence in diabetes mellitus (DM) and ß-Thalassemia patients. We aimed to evaluate the level of serum zinc in ß-thalassemia patients with DM and a risk assessment for hypozincemia. METHODS: The study population included transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) with overt DM (fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-h plasma glucose≥200 mg/dL). Serum zinc concentration was measured by the colorimetric method, and the values below 70 µg/dL were defined as hypozincemia. Myocardial and liver T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) were valued by a free contrast MRI. The demographic, clinical, paraclinical, and laboratory data were also recorded. The data belonged to the period from December 2018 until December 2020. RESULTS: Of 64 diabetic ß-thalassemia patients, 41 cases had zinc data in their medical files (aged 38 ± 9 years, 48.8% female). 78.05% of patients (n = 32) were TDT, and 21.95% were NTDT (n = 9). The mean ± standard deviation of zinc level was 110.2 ± 127.6 µg/dL. The prevalence of hypozincemia was 9.76%, 95% confidence interval [CI] 0.27 to 19.24 (four cases). After controlling age, the odds of hypozincemia for using deferasirox (DFX) was 8.77, 95% CI 0.60 to 127.1. In ß-thalassemia patients, the age-adjusted risk of hypozincemia was calculated at 15.85, 95% CI 0.47 to 529.3 for hepatitis C. The adjusted risk of hypozincemia based on age for antacid use was 6.34, 95% CI 0.39 to 102.7. CONCLUSION: In light of this study, as well as hepatitis C, using DFX and antacids is associated with a high risk of hypozincemia amid diabetic ß-thalassemia cases. However, upward bias should be taken into consideration.

Ferritin thresholds for cardiac and liver hemosiderosis in ß-thalassemia patients: a diagnostic accuracy study.

Ferritin is frequently used to screen some dire consequences of iron overload in ß-thalassemia patients. The study aimed to define the best cutoff point of ferritin to screen for cardiac and liver hemosiderosis in these cases. This was a registry-based study on ß-thalassemia patients living throughout Mazandaran province, Iran (n = 1959). In this diagnostic research, the index test was ferritin levels measured by a chemiluminescent immunoassay. As a reference test, T2*-weighted magnetic resonance imaging (T2*-weighted MRI) was applied to determine cardiac and liver hemosiderosis. A cutoff point of 2027 ng/mL for ferritin showed a sensitivity of 50%, specificity 77.4%, PPV 42.1%, and NPV 82.5% for cardiac hemosiderosis (area under curve [AUC] 0.66, 95% CI 0.60-0.71, adjusted odds ratio [OR] 2.05, 95% CI 1.05-4.01). At an optimum cutoff point of 1090 ng/mL, sensitivity 66.7%, specificity 68%, PPV 82.9%, and NPV 46.8% for liver hemosiderosis were estimated (AUC 0.68, 95% CI 0.63-0.73, adjusted OR 3.93, 95% CI 2.02-7.64. The likelihood of cardiac hemosiderosis serum ferritin levels below 2027 ng/mL is 17.5%. Moreover, 82.9% of ß-thalassemia patients with serum ferritin levels above 1090 ng/mL may suffer from liver hemosiderosis, regardless of the grades.

Detection of Hb Setif in north Iran and the question of its origin: Iranian or multiethnic?

Hb Setif is a rare type of hemoglobinopathy resulting from an aspartic acid to tyrosine substitution at codon 94 (GAC>TAC) of the α2-globin gene. In manual and automated hemoglobin (Hb) electrophoresis examination of the case, an unusual band was detected and the result of subsequent capillary electrophoresis suggested that to be Hb Setif. Carrying out polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing, a typical Hb Setif mutation (GAC>TAC) was identified. The haplotype of the α cluster was + + - M PZ + - - - -. This is the first report of such a hemoglobinopathy in North Iran. Various reports of such Hb variants in Iran and countries in the Mediterranean region and North Africa, suggest that the mutation may have occurred around 6,000 years ago, prior to colonization of Aryans on the Iranian plateau.

Can Use of Silymarin Improve Inflammatory Status in Patients with ß-Thalassemia Major? A Crossover, Randomized Controlled Trial.

BACKGROUND: In ß-thalassemia major (ß-TM) patients, iron overload is one of the main causes of inflammation. This study investigated whether use of silymarin could improve inflammatory status in patients with ß-TM and iron overload, through a placebo-controlled, crossover study. METHODS: Silymarin (140 mg, 3 times a day) or placebo were prescribed to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of silymarin was assessed by measuring serum C-reactive protein (CRP) (mg/dL), interleukin (IL)-6 (pg/mL), and IL-10 (pg/mL). RESULTS: Sixty-nine patients completed the study. Data analysis showed that compared to the placebo, silymarin could decrease CRP, IL-6, and raise IL-10 significantly (the p values for all variables were <0.001). Cohen's d for CRP adjusted according to the baseline CRP value was -1.72, the 95% confidence interval (CI) -2.12 to -1.33. The adjusted Cohen's d equal to -1.12, 95% CI -1.48 to -0.76, and 0.78, 95% CI 0.43-1.12, were also estimated for IL-6 and IL-10, respectively. CONCLUSION: The results of the current study demonstrate that the combination of iron chelation therapy with silymarin can improve inflammatory status in patients with ß-TM in the clinical setting.

Moderate to severe liver siderosis and raised AST are independent risk factors for vitamin D insufficiency in ß-thalassemia patients.

Numerous problematic disorders such as vitamin D (Vit-D) deficiency subsequent to large iron loading can be developed in patients with ß-thalassemia. The study aimed to estimate Vit-D insufficiency and its risk factors in patients with ß-thalassemia. In this multicenter and observational study, all ß-thalassemia patients, who referred to 14 hospital-based thalassemia divisions or clinics in Mazandaran province, Iran were included in the study. The data belong to December 2015 until December 2019. The study population was made of transfusion dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) patients. Serum levels of 25-OHD3 have been measured by high performance liquid chromatography (HPLC) method as ng/mL. Demographic and clinical information along with some biological tests, as well as the results of T2*-weighted magnetic resonance imaging were analyzed. Of 1959 registered patients, 487 (24.9%) patients had Vit-D-related data. The prevalence of Vit-D insufficiency (< 30 ng/mL) was 41.9, 95% CI 37.5-46.3. The adjusted risks of moderate to severe liver siderosis and raised AST (aspartate aminotransferase) for Vit-D insufficiency (< 30 ng/mL) were 2.31, 95% CI 1.38-3.89 and 2.62, 95% CI 1.43-4.79, respectively. The receiver operating characteristic (ROC) curve analysis showed that the predictive accuracy of ferritin for Vit-D insufficiency status was 0.61, 95% CI 0.54-0.68 with a cutoff point of 1,078 ng/mL (P = 0.03, sensitivity 67%, specificity 49%, positive predictive value [PPV] 47% and negative predictive value [NPV] 68%). In spite of the national programs for treating Vit-D deficiency and our previous efforts for giving supplements to all patients, Vit-D insufficiency/deficiency is still common in our patients. Also, moderate to severe liver siderosis and raised AST were the independent risk factors for the Vit-D insufficiency.

Treatment Status of Patients with B-Thalassemia Major in Northern Iran: Thalassemia Registry System.

BACKGROUND: Electronic registry system of beta-thalassemia patients was run by Thalassemia Research Center (TRC) in 2017. The aim of the current study was presentation of therapeutic status in these patients at Mazandaran Province, Iran. METHODS: Therapeutic status variables including: Name of cities and hospitals, age and sex of patients, dependent and non-transfusion-dependent, starting age of the blood transfusion and iron-chelating agents, blood group and Rh, washed blood transfusion, abnormal antibody, transfusion reactions, mean hemoglobin during the last 3 months, type of iron chelators, iron chelators dosage, serum ferritin, and the use of hydroxyurea. RESULTS: Overall, 1831 patients were registered [891 male (48.7%)]. Mean age of patients was 30±9.7 yr. Average of hemoglobin levels for female and male were 9.1±5.1 and 9.4±6.3 gr/dl, respectively. Seventy-six percent of transfusion-dependent patients (1385) have received iso-group PRBC (packed red blood cells), after crossmatch. The most common blood group among patient was type O-positive (35.7%). Monotherapy with desferrioxamine was most type of used iron-chelating agent in these patients (47.2%). Mean of ferritin was 3300±7800 (ng/ml). Twenty-eight percent of patients (484) have received hydroxyurea; proportion of male and female was approximately equal. T2 weighted magnetic resonance imaging (MRIT2*) was measured in 62.2% of patients. Moderate and severe hepatosiderosis was 10.1% and 2.9%, respectively. Patients with moderate and severe cardiac siderosis were 11% and 5%, respectively. CONCLUSION: Registry findings are valuable for treatment management and ensuring patients medications. It will also provide accessibility to various levels of patients' information for health care managers and experts to help them make appropriate decisions.

The improvement of pulmonary artery pressure after bosentan therapy in patients with ß-thalassemia and Doppler-defined pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is relatively prevalent in patients with thalassemia. PAH treatment is necessary as the prevalence of Doppler-estimated PAH and the resultant mortality is high in such patients. MATERIALS AND METHODS: This study aimed at evaluating the effect of bosentan therapy on patients with thalassemia suspected of PAH. Based on pulsed Doppler echocardiography, all the cases were suspected of severe PAH. Consequently, bosentan was initiated at a dose of 62.5 mg twice a day for 4 weeks, which was increased to 62.5-125 mg twice a day, if no adverse side effects were observed. RESULTS: The results of this study showed that pulmonary artery pressure (PAP) decreased after the administration of bosentan in three cases, from 160 to 120, 110 to 65, and 60 to 25 mmHg; in other words, the PAP reduced in the mentioned cases by 25%, 36.4%, and 58.4%, respectively. CONCLUSION: In this study, PAP improved after bosentan therapy in patients with ß-thalassemia suspected of PAH; however, further studies are required to confirm the findings.

Nitroblue tetrazolium test in patients with beta-thalassemia major.

OBJECTIVE: To assess the neutrophil function in thalassemia major (TM) patients and compare it with the control group, and to recognize its relevant factors. METHODS: This was a retrospective cohort study, which was carried out from October 2007 to February 2008 in the Thalassemia Research Center in Boo Ali Sina Hospital in Sari, Mazandaran, north of Iran. The study population consisted of TM patients in Boo Ali Sina Teaching Hospital. The method of sampling in the case group was systematic, and it was target based in the control group. The sample size determined was based on previous studies. Thalassemia major was diagnosed based on hemoglobin electrophoresis (case group). The control group was their brothers and sisters, who had +/-5 years of age difference, and were of the same gender as the patients. Data collection was based on interview, investigating demographic characteristics, and also obtaining medical information from the medical records of the patients. The neutrophil function was assessed by performing nitroblue tetrazolium (NBT) reduction test. The test was carried out on both groups, and the data were analyzed by software using SPSS version 13.0. RESULTS: In this study, 39 patients and 39 healthy controls were compared. The average age of the patients was 21.6 +/- 5.3 years, and it was 22.4 +/- 5.1 years in healthy controls (p=0.7). There was a significant correlation between the tests' results, and the patients' age (p=0.008). The rate of impaired NBT results in the patients was 36%, while it was 10% in controls, which were significantly different. The neutrophil activity based on NBT test was 89.9 +/- 11.6% in the case group, and 93.7 +/- 2.51% in the control group, (p=0.025). CONCLUSION: This study indicates that neutrophil activity in thalassemic patients was significantly lower, compared to the normal control group, especially in young patients. Based on the results, evaluation of neutrophil function, and pyogenic infections in TM patients seems necessary.

Administration of Intravenous Zoledronic Acid Every 3 Months vs. Annually in ß-thalassemia Patients with Low Bone Mineral Density: a Retrospective Comparison of Efficacy.

INTRODUCTION: The benefit of annual administration of zoledronic acid in the management of thalassemia-associated osteoporosis is unknown. AIM: The aims of this study were to evaluate the efficacy of treatment with two different dosing regimens of IV zoledronic acid (annually versus every 3 months) for increasing low bone mineral density (BMD) in patients with osteoporosis associated with ß-thalassemia as annually and 3-monthly on bone density in patients. MATERIALS AND METHODS: This retrospective, single-center study analyzed patients' clinical records and bone density measurements. Those enrolled in the study were 14 to 53 years of age, had documented ß-thalassemia, and were treated with IV zoledronic acid on either an annual or every 3 months dosing regimen. Dual-energy X-ray absorptiometry was used to obtain the z-score for BMD in the lumbar spine and femoral neck. RESULTS: Thirty-four patients were enrolled in the study; 15 (44.1%) had been treated annually, and 19 (55.9%) had been treated every month. In patients receiving treatment with the once-yearly dose of zoledronic acid, significant increases were observed in the lumbar spine BMD z-score, from -2.45 ± 0.69 to -1.97 ± 0.82 (P=0.02). When comparing BMD across the two treatment regimens, the mean lumbar spine BMD was 0.82 greater (95% CI 0.31, 1.33, P=0.003) and the mean femoral neck BMD 0.37 greater (95% CI -0.15, 0.87, P=0.1) in the group receiving annual zoledronic acid treatment. CONCLUSIONS: In patients with thalassemia-associated osteopenia, annual treatment with zoledronic acid increases lumbar spine bone density while being more effective, less expensive, and associated with fewer adverse events than dosing every 3 months.

A randomized, double-blind, controlled trial of testosterone gel treatment versus vehicle control on the facial hair of young men with beta-thalassemia major.

OBJECTIVES: To determine whether the medical prescription of testosterone gel can successfully increase facial hairs in young men with beta-thalassemia major. METHODS: Thirty-two men with beta-thalassemia major, at least 15 years old (tanner stage 4), were randomized in four blocks according to age and serum testosterone level. The cases received 2.5% testosterone gel. The changes in the number of terminal hairs were evaluated by a dermatologist after 6 months. Student's t-test and paired t-test were used to compare the results. RESULTS: The serum testosterone levels of controls and cases were 9.5+/-5.7 (mean+/-SD) and 10.5+/-9.6 ng/l, respectively. The number of terminal hairs (per cm2) in cases (29.8+/-13.6) was significantly higher than that for controls (13.9+/-13.2) (p<0.005). One patient from each group complained of a sense of irritation. CONCLUSION: The 2.5% testosterone gel was effective and well tolerated in inducing the transformation of the terminal hairs of the beard area of thalassemic males.

In Vitro Hb Production in B-thalassemia Patients Is Not a Predictor of Clinical Responsiveness to Hydroxyurea.

BACKGROUND: The hematologic response to hydroxyurea (HU) is varied among ß-thalassemia (BT) patients. The BCL11A and SOX6 genes are involved in response to HU. This study aimed to investigate the in-vitro responsiveness of HU among BT major patients homozygote for IVSII-1G>A mutation and XmnI single nucleotide polymorphism (SNP) in order to find whether the in-vitro Hb concentration is a predictor of clinical (HU) responsiveness. METHODS: In this case-control study, twenty BT patients homozygote for IVSII-1G>A mutation and XmnI SNP from Thalassemia Research Center, Sari, Iran in 2015 were selected and categorized into two groups of 10 Responder (R) and 10 Non-Responder (NR) according to their clinical HU response. Ten healthy individuals as a control group were also selected. Hematopoietic erythroid progenitors were expanded from peripheral blood. Hb concentration was measured using photometry method. The flow cytometry and real-time PCR methods were applied for the analysis of cell surface markers (CD71 and CD235a) and gene expression (BCL11A and SOX6), respectively. RESULTS: R and NR groups produced higher amount of Basic Hb than C group in cell culture medium at day 14 (P<0.05). After HU treatment, in R group, Hb levels was significantly elevated in comparison to NR and C group (P<0.05). BCL11A expression was decreased after exposure to HU in all groups while SOX6 expression was only down-regulated in C group, and its expression was increased in R and NR groups after HU treatment. CONCLUSION: Since different factors including wide networks of intracellular factors and individual differences between patients can affect response to HU in patients, the increasing Hemoglobin on culture medium alone cannot predict clinical responsiveness to that drug.