Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review.

Damoctocog alfa pegol (BAY 94-9027, Jivi), is a site-specifically PEGylated, extended half-life recombinant factor VIII (FVIII) that is approved in several European and non-European countries for on-demand treatment and prophylaxis of bleeding in previously treated patients aged ≥ 12 years with hemophilia A. Reliable measurements can be obtained using most one-stage and chromogenic FVIII assays over a wide concentration range. The efficacy, safety and pharmacokinetics (PK) of damoctocog alfa pegol have been studied extensively in the PROTECT VIII clinical trials, and its long-term safety and effectiveness profile is continuing to build through observational and interventional real-world studies.

Long-Term Efficacy and Safety of Damoctocog Alfa Pegol Prophylaxis in Patients with Haemophilia A Aged 12-<18 Years at Enrolment into PROTECT VIII.

Introduction: The phase 2/3 PROTECT VIII study demonstrated long-term efficacy and safety of damoctocog alfa pegol (BAY 94-9027; Jivi®), a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated to improve its pharmacokinetic profile. We report a post hoc assessment of bleeding and safety outcomes in the subgroup of patients, aged 12-<18 years at enrolment.

Method: PROTECT VIII was a multicentre, open-label study of previously treated males aged 12-65 years with severe haemophilia A (FVIII <1%).

Medical imaging utilization and associated radiation exposure in children with down syndrome.

Objective: To evaluate the frequency of medical imaging or estimated associated radiation exposure in children with Down syndrome.

Methods: This retrospective cohort study included 4,348,226 children enrolled in six U.S.

Simoctocog alfa (Nuwiq®) in previously untreated patients with severe haemophilia A-Final efficacy and safety results from the NuProtect study.

Introduction: Simoctocog alfa (Nuwiq®) is a 4th generation recombinant FVIII with proven efficacy for the prevention and treatment of bleeding episodes (BEs) in previously treated patients with severe haemophilia A. The NuProtect study assessed the immunogenicity, efficacy and safety of simoctocog alfa in 108 previously untreated patients (PUPs). The incidence of high-titre inhibitors was 16.

Long-term immunogenicity, efficacy and tolerability of simoctocog alfa in patients with severe haemophilia A who had completed the NuProtect study in previously untreated patients.

Background: The NuProtect study reported data on the immunogenicity, efficacy and tolerability of simoctocog alfa (Nuwiq ) in 108 previously untreated patients with severe haemophilia A planned to be treated for ≥100 exposure days or up to 5 years. The NuProtect-Extension study collected long-term prophylaxis data in children with severe haemophilia A.

Methods: Patients who completed the NuProtect study according to the protocol were eligible for the NuProtect-Extension study, a prospective, multinational, non-controlled, Phase 3b study.

Eptacog beta efficacy and safety in the treatment and control of bleeding in paediatric subjects (<12 years) with haemophilia A or B with inhibitors.

Introduction: Eptacog beta is a new recombinant activated human factor VII bypassing agent approved in the United States for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors 12 years of age or older.

Aim: To prospectively assess in a phase 3 clinical trial (PERSEPT 2) eptacog beta efficacy and safety for treatment of bleeding in children <12 years of age with haemophilia A or B with inhibitors.

Methods: Using a randomised crossover design, subjects received initial doses of 75 or 225 μg/kg eptacog beta followed by 75 μg/kg dosing at predefined intervals (as determined by clinical response) to treat bleeding episodes (BEs).

The safety of activated eptacog beta in the management of bleeding episodes and perioperative haemostasis in adult and paediatric haemophilia patients with inhibitors.

Introduction: Haemophilia patients with inhibitors often require a bypassing agent (BPA) for bleeding episode management. Eptacog beta (EB) is a new FDA-approved recombinant activated human factor VII BPA for the treatment and control of bleeding in haemophilia A or B patients with inhibitors (≥12 years of age). We describe here the EB safety profile from the three prospective Phase 3 clinical trials performed to date.

PERSEPT 3: A phase 3 clinical trial to evaluate the haemostatic efficacy of eptacog beta (recombinant human FVIIa) in perioperative care in subjects with haemophilia A or B with inhibitors.

Introduction: Surgical procedures in persons with haemophilia A or B with inhibitors (PwHABI) require the use of bypassing agents (BPA) and carry a high risk of complications. Historically, only two BPAs have been available; these are reported to have variable responses.

Aim: To prospectively evaluate the efficacy and safety of a new bypassing agent, human recombinant factor VIIa (eptacog beta) in elective surgical procedures in PwHABI in a phase 3 clinical trial, PERSEPT 3.

Leukemia Risk in a Cohort of 3.9 Million Children with and without Down Syndrome.

Objective: To assess leukemia risks among children with Down syndrome in a large, contemporary cohort.

Study Design: Retrospective cohort study including 3 905 399 children born 1996-2016 in 7 US healthcare systems or Ontario, Canada, and followed from birth to cancer diagnosis, death, age 15 years, disenrollment, or December 30, 2016. Down syndrome was identified using International Classification of Diseases, Ninth and Tenth Revisions, diagnosis codes.

Assessing Safe Discharge Criteria for Pediatric Oncology Patients Admitted for Febrile Neutropenia.

Recent studies suggest outpatient therapy, oral antibiotics, or earlier discharge could be appropriate in some pediatric patients admitted with febrile neutropenia; supporting data are lacking. Retrospective chart review of patients admitted from September 2005 through October 2016 identified 131 "early discharge" febrile neutropenia admissions with discharge absolute neutrophil count (ANC) <500/µl and negative cultures. All were afebrile and discharged without outpatient antibiotics.

Simoctocog Alfa (Nuwiq) in Previously Untreated Patients with Severe Haemophilia A: Final Results of the NuProtect Study.

Introduction:  FVIII inhibitor development is the most serious contemporary treatment complication in haemophilia A, particularly in previously untreated patients (PUPs). No inhibitors developed in clinical trials in previously treated patients treated with simoctocog alfa (Nuwiq), a fourth-generation recombinant FVIII produced in a human cell line.

Methods:  The NuProtect study investigated the immunogenicity of simoctocog alfa in PUPs.

Modelling future usage and cost of factor and emicizumab to treat haemophilia A for the US Western States Region IX haemophilia treatment centres.

Introduction: Increased usage of emicizumab in the United States will affect standard half-life (SHL) and extended half-life (EHL) products usage and cost.

Aim: To model the usage and cost of SHL and EHL products, and emicizumab to treat haemophilia A (HA) in the 13 Western States Region IX haemophilia treatment centres (HTCs.) (California, Nevada, Hawaii and Guam).

Safety and efficacy of BAY 94-9027, an extended-half-life factor VIII, during surgery in patients with severe hemophilia A: Results of the PROTECT VIII clinical trial.

Introduction: Ensuring hemostasis during invasive procedures is a challenge in patients with severe hemophilia A. This analysis evaluated efficacy and safety of BAY 94-9027, an extended-half-life recombinant factor VIII (FVIII), in the surgical setting.

Materials And Methods: Patients participating in an open-label BAY 94-9027 clinical trial who underwent major surgery were included in the analysis.

Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant.

Background: The prevention of bleeding with adequately sustained levels of clotting factor, after a single therapeutic intervention and without the need for further medical intervention, represents an important goal in the treatment of hemophilia.

Methods: We infused a single-stranded adeno-associated viral (AAV) vector consisting of a bioengineered capsid, liver-specific promoter and factor IX Padua (factor IX-R338L) transgene at a dose of 5×10 vector genomes per kilogram of body weight in 10 men with hemophilia B who had factor IX coagulant activity of 2% or less of the normal value. Laboratory values, bleeding frequency, and consumption of factor IX concentrate were prospectively evaluated after vector infusion and were compared with baseline values.

Primary Renal Lymphoma Presenting as End-Stage Renal Disease.

Primary renal lymphoma is a rare entity, even more so in children. Children with primary renal lymphoma present with variable clinical features such as constitutional signs and symptoms, acute kidney injury, palpable abdominal masses, and gross hematuria. Herein we report a child who presented with seemingly advanced chronic kidney disease and was eventually diagnosed with primary lymphoma.

Prospective, multicenter study of postoperative deep-vein thrombosis in patients with haemophilia undergoing major orthopaedic surgery.

Perioperative clotting factor replacement is administered to reverse the inherent haemostatic defect in persons with haemophilia (PWH), potentially increasing their risk for developing venous thromboembolism (VTE) postoperatively. It was our objective to determine the prevalence of VTE in PWH undergoing total hip or knee arthroplasty (THA, TKA). Patients with haemophilia A or B who underwent THA or TKA were enrolled in this prospective, multicentre observational cohort study.

End-Stage Renal Disease From Cast Nephropathy in a Teenager With Neuroendocrine Carcinoma.

Cast nephropathy is the most common manifestation of renal injury in patients with multiple myeloma but is rarely reported in other conditions. We are reporting our experience in caring for a teenager with a metastatic neuroendocrine carcinoma who developed rapidly progressive kidney injury that advanced to end-stage renal disease. On renal biopsy extensive tubular necrosis and intratubular eosinophilic casts were noted.

Dust metal loadings and the risk of childhood acute lymphoblastic leukemia.

We evaluated the relationship between the risk of childhood acute lymphoblastic leukemia (ALL) and the levels of metals in carpet dust. A dust sample was collected from the homes of 142 ALL cases and 187 controls participating in the California Childhood Leukemia Study using a high volume small surface sampler (2001-2006). Samples were analyzed using microwave-assisted acid digestion in combination with inductively coupled plasma mass spectrometry for arsenic, cadmium, chromium, copper, lead, nickel, tin, tungsten, and zinc.

Alprolix (recombinant Factor IX Fc fusion protein): extended half-life product for the prophylaxis and treatment of hemophilia B.

Hemophilia B is a genetic disease caused by mutation of the gene for coagulation protein Factor IX. When severe, the disease leads to spontaneous life-threatening bleeding episodes. Current therapy requires frequent intravenous infusions of therapeutic recombinant or plasma-derived protein concentrates containing Factor IX.

WARM N COLD: malignant and benign renal tumors in children.

Although Wilms tumor is the most common renal malignancy in children, the differential diagnosis is extensive and includes both malignant and benign disorders. We present a simple mnemonic-WARM N COLD, to aid in remembering these diverse tumors. Imaging clues including age of the patient, associated disease or syndrome as well as salient imaging characteristics such as bilaterality, and type or presence of metastasis are also presented and can help differentiate between these renal tumors of childhood.

Tobacco smoke exposure and the risk of childhood acute lymphoblastic and myeloid leukemias by cytogenetic subtype.

Background: Tobacco smoke contains carcinogens known to damage somatic and germ cells. We investigated the effect of tobacco smoke on the risk of childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML), especially subtypes of prenatal origin such as ALL with translocation t(12;21) or high-hyperdiploidy (51-67 chromosomes).

Methods: We collected information on exposures to tobacco smoking before conception, during pregnancy, and after birth in 767 ALL cases, 135 AML cases, and 1,139 controls (1996-2008).

Children and adolescents with ALL are taller than expected at diagnosis.

We investigated whether the relative increased height of childhood acute lymphoblastic leukemia (ALL) survivors at diagnosis was due to referral bias, the height of California children, socio-economic status, or race/ethnicity. We reviewed the records of all Pediatric Oncology referrals to our institution from 1988 to 2007. Height at diagnosis, sex, age at and date of diagnosis, date of birth, diagnosis, race/ethnicity, and socio-economic status were evaluated.