Results from a large multinational clinical trial (guardian™3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A: safety, efficacy and pharmacokinetics.

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prophylaxis and treatment of bleeding episodes in patients with severe haemophilia A. This multinational, open-label, non-controlled trial investigated the safety, efficacy and pharmacokinetics (PK) of turoctocog alfa, a new rFVIII product, in a paediatric population. The primary objective was to evaluate safety. A total of 31 younger children (0-5 years) and 32 older children (6-11 years), with ≥ 50 exposure days to any factor VIII (FVIII) product and no history of inhibitors, received prophylaxis with turoctocog alfa (25-50 IU kg(-1) every second day or 25-60 IU kg(-1) three times weekly). PK assessments of turoctocog alfa and the patients' previous FVIII product were performed in 28 patients. Mean exposure to turoctocog alfa was 60 exposure days per patient. This corresponds to approximately 4.5 months in the trial. None of the patients developed inhibitors (≥ 0.6 BU) and no safety concerns were raised. A total of 120 bleeding episodes (95%) were controlled with 1-2 infusions of turoctocog alfa. Based on patient reports, the success rate (defined as 'excellent' or 'good' haemostatic response) for treatment of bleeding episodes was 92%. Overall, the median annualized bleeding rate was 3.0 (interquartile range: 8.5) bleeds patient(-1) year(-1) . PK parameters were comparable between the two age groups. In conclusion, the present large global clinical trial showed that turoctocog alfa was safe, effective in treatment of bleeding episodes and had a prophylactic effect in paediatric patients.

Progression of haemophilic arthropathy in children: a Lithuanian--Danish comparative study.

Recurrent bleeding into joints initiates a sequence of events leading to a progressive joint damage in people with severe haemophilia. This is a continuous process during childhood and adolescence, therefore joint abnormalities may be minimal on physical examination in very young children - even those receiving on-demand treatment. The aim of our study was to quantify the burden of arthropathy in Lithuanian patients who had been treated exclusively by on-demand substitution and compare their physical joint health with age-matched Danish patients who received prophylaxis from an early age. Boys, aged 4-17 years, with severe haemophilia and no signs of inhibitors were included in the study. Joint outcome based on the Haemophilia Joint Health Score (HJHS) was analysed in two different treatment groups and compared within the matched pairs. In total, 32 (16 in each treatment group) patients were enroled. A total of 192 joints were evaluated. Joint status according to treatment strategy was strikingly different: 27.4 for on-demand vs. 3.3 for prophylaxis (<0.001) group. Significance of the difference in joint status comparing different treatment strategies was equally strong both in younger (4-9 years) and older (10-17 years) patient groups: 2.2 vs. 12.5 (P = 0.0002) and 3.9 vs. 36.3 (P < 0.0001) respectively. The results further demonstrate the unequivocal effect of prophylaxis on joint status and give an insight into early and late manifestations of joint impairment based on the HJHS in haemophilia patients with treatment on-demand compared with joint changes that may develop over the time with the preventative treatment.

The state of research into children with cancer across Europe: new policies for a new decade.

Overcoming childhood cancers is critically dependent on the state of research. Understanding how, with whom and what the research community is doing with childhood cancers is essential for ensuring the evidence-based policies at national and European level to support children, their families and researchers. As part of the European Union funded EUROCANCERCOMS project to study and integrate cancer communications across Europe, we have carried out new research into the state of research in childhood cancers. We are very grateful for all the support we have received from colleagues in the European paediatric oncology community, and in particular from Edel Fitzgerald and Samira Essiaf from the SIOP Europe office. This report and the evidence-based policies that arise from it come at a important junction for Europe and its Member States. They provide a timely reminder that research into childhood cancers is critical and needs sustainable long-term support.

Utility of the Haemophilia Joint Health Score in study of episodically treated boys with severe haemophilia A and B in Lithuania.

Musculoskeletal outcome remains the major hallmark of haemophilia. The purpose of the study was to assess joint status using a new musculoskeletal assessment tool in children with haemophilia and describe the development of haemophilic arthropathy during childhood and puberty focussing on the age of remarkable changes. The prospective study involved Lithuanian patients aged 4-17 years with severe haemophilia A and B, no signs of inhibitors and treatment on-demand. Patients were subdivided into two groups according to actual age. Group I patients were 4-9 years and group II patients 10-17 years of age. The musculoskeletal status was measured using the Haemophilia Joint Health Score (HJHS). We report on 20 patients with a mean age of 11.5 years (SD 4.3, range 4-17.2 years). The mean HJHS score was 24.5 (SD 14.5, range 5-50). The most affected joints were ankles, followed by knees and elbows. Mean HJHS score in age group I (n = 7) was 11.6 (SD 6.5); in group II (n = 13) the score was significantly higher - mean 31.5 (SD 12.8) (P = 0.0002). Ankles, knees and elbows were significantly more impaired based on the HJHS scores in older patients as compared with younger ones. The HJHS appears to be a useful tool in evaluating musculoskeletal outcome of patients receiving treatment on-demand. Children > or =10 years of age had significantly higher HJHS scores as a sign of progressing haemophilic arthropathy. We conclude that the most aggravating development of haemophilic joint damage seems to occur from the age of 10 and onwards.

Insulin-degrading activity and insulinase-inhibiting activity in acute leukemia.

Insulin-degrading and insulinase-inhibiting activity of whole blood and erythrocytes of 146 children affected with acute leucosis of different stages were investigated. No statistically reliable difference between the data of insulin-degrading activity in acute leucosis and healthy children was found. Insulinase-inhibiting activity of both the hemolysate of blood and erythrocytes was increased in children in the active stage of the disease.