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Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs ≥1% has shown to be efficacious with an acceptable safety profile in people with hemophilia A (PwHA). The PROPEL trial compared safety and efficacy of 2 target FVIII troughs in PwHA aged 12 to 65 years, with severe disease, annualized bleeding rate ≥2, and previous FVIII treatment. PwHA were randomized to 12 months’ pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1% to 3% (reference arm) or 8% to 12% (elevated arm); first 6 months was treatment-adjustment period. The primary endpoint was absence of bleeds during the second 6 months, analyzed using multiple imputations (full analysis set [FAS]). In the 1% to 3% and 8% to 12% arms, respectively, point estimates (95% confidence interval) of proportions of PwHA with zero total bleeds were 42% (29% to 55%) and 62% (49% to 75%) in FAS (N = 115; P = .055) and 40% (27% to 55%) and 67% (52% to 81%) in per-protocol analysis set (N = 95; P = .015). Dosing frequency and consumption varied in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA; serious AEs in 7/115 (6%) PwHA, including 1 treatment-related in 8% to 12% arm (transient anti–FVIII inhibitor). There were no deaths, serious thrombotic events, or AE-related discontinuations. PK-guided prophylaxis was achievable and efficacious in both arms. No new safety signals were observed in the 8% to 12% arm. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and emphasize the importance of personalized treatment. This trial was registered at www.clinicaltrials.gov as #NCT02585960.

ObjectiveThalassaemia is the most common inherited blood disorder in Malaysia. This study aims to report the current status of thalassaemia in Malaysia and provide a comprehensive understanding of the disease through data obtained from the Malaysian Thalassaemia Registry.DesignData were extracted from the Malaysian Thalassaemia Registry, a web-based system accessible to enrolled users through www.mytalasemia.net.my.SettingThe Malaysian Thalassaemia Registry data was recorded from reports obtained from 110 participating government and university hospitals in Malaysia.ParticipantsThe patients were those attending the 110 participating hospitals for thalassaemia treatment.InterventionData were collected from the Malaysian Thalassaemia Registry from 2007 until the fourth quarter of 2018.Primary outcome measure7984 out of 8681 patients with thalassaemia registered in the Malaysian Thalassaemia Registry were reported alive.ResultsMajority of the patients were reported in the state of Sabah (22.72%); the largest age group affected was 5.0–24.9 years old (64.45%); the largest ethnic group involved was Malay (63.95%); and the major diagnosis was haemoglobin E/β-thalassaemia (34.37%). From the 7984 patients, 56.73% were on regular blood transfusions and 61.72% were on chelation therapy. A small fraction (14.23%) has undergone splenectomy, while the percentage of patients with severe iron overload (serum ferritin ≥5000 µg/L) reduced over time. However, cardiac complications are still the main cause of death in patients with thalassaemia.ConclusionData gathered into the registry can be used to understand the progression of the disorder, to monitor iron overload management and to improve the outcomes of treatment, to enhance preventive strategies, reduce healthcare burden and improve the quality of life. Sustainability of the Malaysian Thalassaemia Registry is important for surveillance of thalassaemia management in the country and help the national health authorities to develop more effective policies.

This is the first report of QQQ-mass spectrometric identification and quantification of the Hb subunits, alpha, beta, delta and gamma globin peptides, derived from enzymatic-digestion of proteins in the early unknown peaks of the Bio-Rad cation-exchange chromatography of haemoglobin. The objectives were to assess the relationship of the quantity of the free alpha, beta, delta and gamma globin chains with the phenotypic diversity of beta-thalassaemias (β-thal). The results demonstrate that the pools of free globin chains in red blood cells were correlating with the severity of the disease in patients with different phenotypes of β-thal. The mechanism and the regulation of synthesis of free globin chains pool in a normal individual and in patients with different β-thal phenotypes could arise from several mechanisms which will require further investigation. The role of the free globin pool in patients with β-thal for development of novel therapeutic approaches based on these potential targets requires further investigation. Pertinent biomarkers improves the diagnosis of the β-thal, especially in low-income countries where they are most common and allows more effective therapeutic intervention leading to more successful therapeutic outcome. Keywords: Anaemia, Thalassemia, Mass spectrometry, Globin chain, Quantification, HPLC, Unknown peaks

PubMed ID: 22271905, Background Prospective data on cardiac iron removal are limited beyond one year and longer-term studies are, therefore, important. Design and Methods Seventy-one patients in the EPIC cardiac substudy elected to continue into the 3 rd year, allowing cardiac iron removal to be analyzed over three years. Results Mean deferasirox dose during year 3 was 33.6±9.8 mg/kg per day. Myocardial T2*, assessed by cardiovascular magnetic resonance, significantly increased from 12.0 ms ±39.1% at baseline to 17.1 ms ±62.0% at end of study (P5 to

WOS: 000286902400010, PubMed ID: 21071497, Background The efficacy of cardiac iron chelation in transfusion-dependent patients has been demonstrated in one-year prospective trials. Since normalization of cardiac T2* takes several years, the efficacy and safety of deferasirox was assessed for two years in patients with beta-thalassemia major in the cardiac sub-study of the EPIC trial. Design and Methods Eligible patients with myocardial T2* greater than 5 to less than 20 ms received deferasirox, with the primary endpoint being the change in T2* from baseline to two years. Results Baseline myocardial T2* was severe (>5 to = 5%) increased serum creatinine, rash and increased alanine aminotransferase. Conclusions Continuous treatment with deferasirox for two years with a target dose of 40 mg/kg/d continued to remove iron from the heart in patients with beta-thalassemia major and mild, moderate and severe cardiac siderosis. (Clinicaltrials.gov identifier: NCT 00171821), Novartis Pharma AG; British Heart FoundationBritish Heart Foundation [PG/09/074/27961]; National Institute for Health ResearchNational Institute for Health Research (NIHR) [NF-SI-0508-10081], this study was sponsored by Novartis Pharma AG. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals.

Thalassaemia, a common inherited haemoglobinopathy in Malaysia1, causes significant morbidity due to chronic anaemia and complications of iron excess from regular blood transfusion. Short stature is one of the commonest complications in transfusion-dependent thalassaemia with prevalence of 31% to 75% 2,3. Causes of growth impairment include iron overload, nutritional deficiency, GH-IGF1 axis dysregulation, abnormal puberty and desferrioxamine toxicity4,5. We aim to determine the prevalence of short stature, defined as height z-score ≤ -2, and the factors affecting height in thalassaemia patients attending the Haematology clinic at a tertiary referral center. This observational cross-sectional study involved patients aged 3-19 years, needing blood transfusion at least every 8 weeks, and without co-morbidities or endocrinopathy which affect growth. Weight & height were measured. Puberty status was clinically assessed. Body mass index (BMI) was calculated as a marker of nutritional status. Mean of ferritin levels measured over the preceding one year was determined as a marker of iron overload. There were 52 boys (mean age 11.2y ± 4.8y, mean height z-score -1.67 ± 1.11, mean BMI z- score -0.87 ± 1.44, mean ferritin 3316 ± 2092 µg/L) and 47 girls ( mean age 11.8y ± 4.2y, mean height z-score -1.59 ± 0.97 , mean BMI z-score -0.83 ± 0.95, mean ferritin 3005 ± 2356 µg/L). Overall 35/99 (35%) were short while 64/99 (64%) had normal height. 19/52 (37%) boys and 16/47 (34%) girls were short. 16/19 (84%) short boys were aged ≥ 9 years, 15/16 (94%) short girls were aged ≥ 8 years. Only one boy (aged 15y) and one girl (aged 14y) had delayed puberty. They were both short with height z-score -3.41 and -2.26 respectively. Overall there was a moderate positive correlation between height z-score and BMI z- score (Pearson r = 0.388, p=0.00). There was no significant correlation between height z score and mean ferritin level (Pearson r = -0.044, p= 0.666). Significant proportion (35%) of our transfusion-dependent thalassaemia patients have short stature, majority of them in the pubertal age group. Height is significantly associated with nutritional status but not ferritin level. Improvement in nutrition may improve height in these patients.