Publications by authors named "Quon D"
Clinical Features: Sickle cell patients may develop a multitude of antibodies and experience life-threatening events with transfusion such as hyperhemolysis syndrome or delayed hemolytic transfusion reaction. Further transfusion may not be possible in such cases.
Therapeutic Challenge: When conventional blood products are not available for transfusion yet the patient requires additional oxygen-carrying support, artificial oxygen carriers may be required.
Background: Hemophilia A is caused by coagulation factor VIII (FVIII) deficiency and increases bleeding risk during invasive procedures.
Objectives: To investigate FVIII concentrate use and bleeding outcomes for invasive procedures after valoctocogene roxaparvovec gene transfer.
Design: This manuscript presents post hoc analysis of the phase III GENEr8-1 trial.
Background: Valoctocogene roxaparvovec, an adeno-associated virus-mediated gene therapy for severe hemophilia A, enables endogenous factor (F)VIII expression and provides bleed protection.
Objectives: Determine valoctocogene roxaparvovec durability, efficacy, and safety 4 years after treatment.
Methods: In the phase 3 GENEr8-1 trial, 134 adult male persons with severe hemophilia A without inhibitors and previously using FVIII prophylaxis received a 6 × 10 vg/kg infusion of valoctocogene roxaparvovec.
Background: Little information regarding the management of invasive procedures in people with hemophilia B (HB) after undergoing gene therapy is available. Here, we report the management of invasive procedures in people with severe or moderately severe HB who had previously been treated with etranacogene dezaparvovec in the phase 2b and phase 3 Health Outcomes with Padua Gene; Evaluation in Hemophilia B clinical trials (NCT03489291 and NCT03569891).
Objectives: The objective of this study was to describe the use of exogenous FIX, endogenous FIX activity prior to invasive procedures, and peri- and postoperative bleeds in participants who underwent invasive procedures after receiving etranacogene dezaparvovec gene therapy.
Background: Valoctocogene roxaparvovec transfers a human factor (F)VIII coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection.
Objectives: To present 3-year efficacy and safety in the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial.
Methods: GENEr8-1 enrolled 134 adult males with severe hemophilia A who were receiving FVIII prophylaxis.
Purpose: CB-103 selectively inhibits the CSL-NICD (Notch intracellular domain) interaction leading to transcriptional downregulation of oncogenic Notch pathway activation. This dose-escalation/expansion study aimed to determine safety, pharmacokinetics, and preliminary antitumor activity.
Experimental Design: Patients ≥18 years of age with selected advanced solid tumors [namely, adenoid cystic carcinoma (ACC)] and hematologic malignancies were eligible.
Background: Intratumoral injection of talimogene laherparepvec evokes a cytotoxic immune response. Therefore, the combination of talimogene laherparepvec with trabectedin and nivolumab may have synergistic effects in advanced sarcomas.
Patients And Methods: This phase 2 trial was conducted from May 30, 2019 to January 31, 2022.
Background/aim: Advanced sarcoma has a poor prognosis. Dysregulation of the mammalian target of rapamycin (mTOR) occurs in various types of cancer. We aimed to determine the safety and efficacy of mTOR inhibitor nab-sirolimus when combined with the immune checkpoint inhibitor nivolumab.
View Article and Find Full Text PDFObjectives: The Joint Activity and Damage Exam (JADE) is a point-of-care (POC) musculoskeletal ultrasound (MSKUS) protocol for non-radiologists to evaluate hemophilic arthopathy. Our aim was to determine the consistency of cross-sectional analyses of direct tissue measurements (JADE protocol) and clinical Hemophilia Joint Health Score [HJHS] and functional joint assessments (arc) at three clinic visits.
Methods: We prospectively studied adults (n = 44) with hemophilia (A or B) of any severity and arthropathy at 3 North American sites.
Background: Decades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates the effects of gene therapy (etranacogene dezaparvovec) for treating moderate-to-severe hemophilia B, comparing it with traditional factor IX replacement therapy.
- A phase 3 open-label trial involved 54 men who received a single infusion of AAV5 vector after a lead-in period of factor IX prophylaxis, with the goal of reducing annualized bleeding rates.
- Results showed a significant decrease in bleeding rates from 4.19 to 1.51 and an increase in factor IX activity, demonstrating that gene therapy is not only noninferior but also superior to standard treatment.
Background: Valoctocogene roxaparvovec delivers a B-domain-deleted factor VIII coding sequence with an adeno-associated virus vector to prevent bleeding in persons with severe hemophilia A. The findings of a phase 3 study of the efficacy and safety of valoctocogene roxaparvovec therapy evaluated after 52 weeks in men with severe hemophilia A have been published previously.
Methods: We conducted an open-label, single-group, multicenter, phase 3 trial in which 134 men with severe hemophilia A who were receiving factor VIII prophylaxis received a single infusion of 6×10 vector genomes of valoctocogene roxaparvovec per kilogram of body weight.
Background: This Phase 1/2 study is based on the hypothesis that immune checkpoint inhibitors are more effective when given earlier in the course of the disease for advanced soft tissue sarcoma.
Methods: Phase I endpoints-maximum tolerated dose in previously treated patients; Phase II endpoints-best response, progression free survival and overall survival and incidence of adverse events in previously untreated patients; Phase I treatments-escalating doses of trabectedin (1.0, 1.
Background: The use of musculoskeletal ultrasound (MSKUS) for point-of-care (POC) evaluation of hemophilic arthropathy is growing rapidly. However, the extent to which MSKUS influences clinical treatment decisions is unknown.
Methods: We conducted a three-year, prospective, multi-center study at three hemophilia treatment centers in the United States to evaluate the utilization of POC-MSKUS for routine clinical decision-making in adult persons with hemophilic arthropathy.
Innovative treatments are urgently needed for metastatic cancer. DeltaRex-G, a tumor-targeted retrovector encoding a dominant-negative/cytocidal cyclin G1 (CCNG1 gene) inhibitor construct-has been tested in over 280 cancer patients worldwide in phase 1, phase 2 studies and compassionate use studies, demonstrating long term (>10 years) survivorship in patients with advanced cancers, including pancreatic cancer, osteosarcoma, malignant peripheral nerve sheath tumor, breast cancer, and B-cell lymphoma. Endpoints: Survival, response, treatment-related adverse events.
View Article and Find Full Text PDFIntroduction: The reasons for the high prevalence of hypertension in persons with haemophilia (PWH) are poorly understood.
Aim: To examine the roles of diabetes, Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) in the etiology of hypertension for PWH.
Methods: Retrospective cross-sectional design.
Introduction: Persons with haemophilia (PWH) have a higher prevalence of hypertension compared to the general population, which cannot be explained entirely by the usual cardiovascular risk factors. Neutralizing antibodies (inhibitors) against clotting factors might have some relation to cardiovascular disease in PWH. However, whether inhibitors facilitate hypertension is unknown.
View Article and Find Full Text PDFBackground: Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is an adeno-associated virus 5 (AAV5)-based gene-therapy vector containing a coagulation factor VIII complementary DNA driven by a liver-selective promoter. The efficacy and safety of the therapy were previously evaluated in men with severe hemophilia A in a phase 1-2 dose-escalation study.
Methods: We conducted an open-label, single-group, multicenter, phase 3 study to evaluate the efficacy and safety of valoctocogene roxaparvovec in men with severe hemophilia A, defined as a factor VIII level of 1 IU per deciliter or lower.
Introduction: Ageing patients with haemophilia (PWH) develop cardiovascular risk factors impacting care. Little is known about the prevalence of diabetes in PWH and its relation to other comorbidities.
Aim: To examine the risk of diabetes for adult PWH compared to men from the general United States population (National Health and Nutrition Examination Surveys [NHANES]) and outpatients attending a Veterans Affairs Medical Center (VAMC) clinic.
Adeno-associated virus (AAV)-mediated gene therapy may provide durable protection from bleeding events and reduce treatment burden for people with hemophilia A (HA). However, pre-existing immunity against AAV may limit transduction efficiency and hence treatment success. Global data on the prevalence of AAV serotypes are limited.
View Article and Find Full Text PDFBackground: Persons with hemophilia (PWH) are at risk for chronic hemophilic arthropathy (HA). Joint replacement surgery may be used to relieve intractable pain and/or restore joint function.
Objectives: This multicenter, prospective, observational cohort study evaluated the rate of bleeding during the postoperative period after total hip (THA) or knee arthroplasty (TKA).
To determine the feasibility of patients to use a web-based health app for management of post-concussion (mTBI) symptoms in an out-patient setting. Seven (7) patients who were referred to an outpatient specialist clinic (physiatry) with persisting symptoms following a concussion. Participants had to be 18 years of age or older and more than 3 months post injury.
View Article and Find Full Text PDFIntroduction: High collision-risk physical activity can increase bleeding risk in people with hemophilia A, as can increasing the time between factor VIII (FVIII) administration and physical activity. FVIII prophylaxis may be tailored to planned activities to prevent activity-related bleeding.
Aim: To explore the relationship between physical activity levels, FVIII infusion timing, and occurrence of bleeding in patients with severe/moderately severe hemophilia A without FVIII inhibitors receiving antihemophilic factor (recombinant) (rAHF; ADVATE; Baxalta US Inc.