BAY 81-8973 Demonstrates Long-Term Safety and Efficacy in Children With Severe Haemophilia A: Results From the LEOPOLD Kids Extension Study.

Objectives: To report the long-term safety and efficacy of BAY 81-8973 in the LEOPOLD Kids extension phase.

Methods: Patients received BAY 81-8973 (25-50 IU/kg) at least twice weekly. The primary endpoint was safety, assessed in all patients who entered the extension phase (n = 82).

Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial.

Background: Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody in development as a once-daily, subcutaneous prophylaxis for patients with haemophilia A or haemophilia B with or without inhibitors. We aimed to assess the efficacy and safety of concizumab in patients with haemophilia A or B without inhibitors. Here we report the results from the confirmatory analysis cutoff.

Sequelae and post-thrombotic syndrome after venous thromboembolism in acute lymphoblastic leukemia survivors treated on the NOPHO ALL2008 protocol.

The treatment of acute lymphoblastic leukemia (ALL) is frequently complicated by toxicity, including venous thromboembolism (VTE) affecting roughly 8% of patients. VTE can lead to post-thrombotic syndrome (PTS), a group of signs and symptoms developed as a complication to deep venous thrombosis (DVT), imposing risk of permanent disability and reduced quality of life (QoL). PTS prevalence ranges from 0% to 70%, reflecting very heterogenous cohorts and assessment tools.

BAY 81-8973 Efficacy and Safety in Previously Untreated and Minimally Treated Children with Severe Hemophilia A: The LEOPOLD Kids Trial.

Introduction:  BAY 81-8973, a full-length recombinant factor VIII for hemophilia A treatment, has been extensively evaluated in previously treated patients in the LEOPOLD (Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease) clinical trials.

Aim:  To assess BAY 81-8973 efficacy and safety when used for bleed prophylaxis and treatment in previously untreated/minimally treated patients (PUPs/MTPs).

Methods:  In this phase III, multicenter, open-label, uncontrolled study, PUPs/MTPs (<6 years old) with severe hemophilia A received BAY 81-8973 (15-50 IU/kg) at least once weekly as prophylaxis.

A survey on thromboprophylaxis and coagulation assessment in children and young adults with acute lymphoblastic leukaemia (ALL) in the Nordic and Baltic countries: Different practices of assessment and management.

Patients undergoing treatment for acute lymphoblastic leukaemia (ALL) are at risk of coagulopathy, especially thromboembolism. We conducted a survey on practices in the assessment and management of coagulopathy during the new ALLTogether protocol in 29 (17 paediatric, 12 adult) Nordic and Baltic cancer centres. While 92% of adult centres used thromboprophylaxis with low-molecular-weight heparin, no paediatric centre did.

Illustrative Cases from the Pathfinder Clinical Trials of Patients with Hemophilia A Treated with Turoctocog Alfa Pegol (N8-GP).

Purpose: To illustrate the benefits of the extended half-life (EHL) recombinant factor VIII product N8-GP (Esperoct, turoctocog alfa pegol) by describing individual cases of patients with severe hemophilia A treated with N8-GP in the pathfinder clinical trial program.

Patients And Methods: This manuscript presents selected patient cases from the pivotal pathfinder clinical trial program, which included a number of clinical studies in adults (pathfinder 2 and 3) and children (pathfinder 5); overall results published previously. Clinical data and outcomes described in this manuscript are more detailed and derived from several interesting patient cases (five adults from pathfinder 2 and two children from pathfinder 5), who received N8-GP as prophylaxis (PPX) for their severe hemophilia A.

Endothelial dysfunction and thromboembolism in children, adolescents, and young adults with acute lymphoblastic leukemia.

Endothelial dysfunction has not previously been investigated as a thrombogenic risk factor among patients with acute lymphoblastic leukemia (ALL), known to be at high risk of thromboembolism. We retrospectively explored the association between three circulating biomarkers of endothelial dysfunction (thrombomodulin, syndecan-1, VEGFR-1) measured in prospectively collected blood samples and risk of thromboembolism in 55 cases and 165 time-matched controls, treated according to the NOPHO ALL2008 protocol. In age-, sex-, and risk group-adjusted analysis, increasing levels of thrombomodulin and VEGFR-1 were independently associated with increased odds of developing thromboembolism (OR 1.

Shortening the paediatric Haemophilia Activities List (pedHAL) based on pooled data from international studies.

Introduction: The paediatric Haemophilia Activities List (pedHAL) was developed to measure activities and participation in children and youth with haemophilia. Results from international studies provide an opportunity to determine which items are universally important.

Aim: The aim of this study was to determine which items of the pedHAL are redundant to construct a shorter version of the pedHAL.

Evaluating international Haemophilia Joint Health Score (HJHS) results combined with expert opinion: Options for a shorter HJHS.

Introduction: The Hemophilia Joint Health Score (HJHS) was developed to detect early changes in joint health in children and adolescents with haemophilia. The HJHS is considered by some to be too time consuming for clinical use and this may limit broad adoption.

Aim: This study was a first step to develop a shorter and/or more convenient version of the HJHS for the measurement of joint function in children and young adults with haemophilia, by combining real-life data and expert opinion.

Long-term safety and efficacy of N8-GP in previously treated pediatric patients with hemophilia A: Final results from pathfinder5.

Background: N8-GP (turoctocog alfa pegol; Esperoct , Novo Nordisk A/S, Bagsvaerd, Denmark) is a glycoPEGylated, extended half-life human recombinant factor VIII (FVIII).

Objective: Here, we report end-of-trial safety and efficacy results from the completed N8-GP pathfinder5 trial.

Methods: pathfinder5 (NCT01731600) was a multi-national, open-label, single-arm, non-randomized, non-controlled trial in previously treated male patients aged <12 years old with severe hemophilia A that comprised a main and an extension phase.

Polygenic risk score-analysis of thromboembolism in patients with acute lymphoblastic leukemia.

Introduction: Thromboembolism (TE) is a common and serious toxicity of acute lymphoblastic leukemia (ALL) treatment, but studies of genetic predisposition have been underpowered with conflicting results. We tested whether TE in ALL and TE in the general adult population have a shared genetic etiology.

Materials And Methods: We prospectively registered TE events and collected germline DNA in patients 1.

Pulmonary embolism in acute lymphoblastic leukemia - An observational study of 1685 patients treated according to the NOPHO ALL2008 protocol.

Background: Pulmonary embolism (PE) is a serious complication of acute lymphoblastic leukemia (ALL). We examined the cumulative incidence and clinical presentation of PE in a well-defined cohort of patients with ALL aged 1-45 years treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol.

Methods: As part of the mandatory toxicity reporting of NOPHO ALL2008, thromboembolism including PE was reported consecutively.

Continued benefit demonstrated with BAY 81-8973 prophylaxis in previously treated children with severe haemophilia A: Interim analysis from the LEOPOLD Kids extension study.

Introduction: BAY 81-8973 (Kovaltry®), a recombinant factor VIII (rFVIII) product, was efficacious and well tolerated in paediatric previously treated patients (PTPs) with severe haemophilia A for ≥50 exposure days (EDs) in the LEOPOLD Kids study. Because long-term prophylaxis (≥100 EDs) can provide substantial patient benefits, FVIII products should demonstrate long-term safety and efficacy.

Aim: To demonstrate long-term (≥100 EDs) efficacy and safety of BAY 81-8973 in paediatric PTPs.

Candidate single nucleotide polymorphisms and thromboembolism in acute lymphoblastic leukemia - A NOPHO ALL2008 study.

Introduction: Thromboembolism is a serious toxicity of acute lymphoblastic leukemia treatment, and contributes to substantial morbidity and mortality. Several single nucleotide polymorphisms have been associated with thromboembolism in the general population; however, their impact in patients with acute lymphoblastic leukemia, particularly in children, remains uncertain.

Materials And Methods: We collected constitutional DNA and prospectively registered thromboembolic events in 1252 patients, 1-45 years, with acute lymphoblastic leukemia included in the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol in the Nordic and Baltic countries (7/2008-7/2016).

Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years.

Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during the treatment of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol (July 2008-April 2017). The 2.

A rare case of unprovoked venous thromboembolism manifestation in a young patient with antithrombin Type IIB deficiency combined with inferior vena cava anomaly from Lithuania.

Unlabelled: Hereditary antithrombin (AT) deficiency is an autosomal-dominant disorder predisposing to venous and arterial thrombosis. Homozygosity resulting in severe AT deficiency is not compatible with life, apart from homozygous mutations affecting the heparin-binding site representing the most severe thrombophilia.

Patients And Methods: A 12-year-old previously healthy boy of Romani origin presented with a swollen, painful left leg and fever.

Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology.

We present a prospective multicentre cohort of 20 children with acute lymphoblastic leukaemia (ALL) and cerebral sinus venous thrombosis (CSVT). The study covers a period of 5 years and comprises 1038 children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL 2008 protocol. The cumulative incidence of CSVT was 2%.

On-demand treatment in persons with severe haemophilia.

There are two main modes of replacement therapy for haemophilia patients: either to stop bleeding (on-demand) or regular infusions of clotting factor to prevent bleeds (prophylaxis). Fifty yr of clinical experience have provided evidence of the superiority of prophylaxis by showing a reduction in bleeds and development of arthropathy. Prophylaxis has been described extensively in terms of efficacy and health-economic aspects; however, on-demand treatment has received less attention.