A5079102665- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Blood groups and transfusion
- Prenatal Screening and Diagnostics
- Erythrocyte Function and Pathophysiology
- Acute Lymphoblastic Leukemia research
- Bone and Joint Diseases
- Virus-based gene therapy research
- Pharmacological Effects and Toxicity Studies
- Blood disorders and treatments
- CRISPR and Genetic Engineering
- Neonatal Health and Biochemistry
- Folate and B Vitamins Research
- Pregnancy and preeclampsia studies
- Parvovirus B19 Infection Studies
- Hematopoietic Stem Cell Transplantation
- Erythropoietin and Anemia Treatment
- Neuroblastoma Research and Treatments
- Hepatitis B Virus Studies
- Blood properties and coagulation
- Cancer, Hypoxia, and Metabolism
- Trace Elements in Health
- Hepatitis C virus research
- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
Children's Hospital of Philadelphia
2016-2025
University of Pennsylvania
2015-2024
Cornell University
2004-2024
University College London
2004-2024
Magna Graecia University
2024
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
2024
Bambino Gesù Children's Hospital
2024
Heinrich Heine University Düsseldorf
2024
Düsseldorf University Hospital
2024
Ospedale Maggiore
2024
Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent β-thalassemia. After previously establishing that lentiviral transfer a marked β-globin (βA-T87Q) gene could substitute for long-term red-cell transfusions patient β-thalassemia, we wanted to evaluate safety efficacy such therapy
Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and associated recurrence of an infarct (stroke or silent infarct). We tested hypothesis that incidence would be lower among who underwent regular blood-transfusion therapy than those received standard care.In this randomized, single-blind clinical trial, we randomly assigned to receive blood transfusions (transfusion group) care (observation group). Participants were between 5 15 years age, no...
Red cell transfusions remain a mainstay of therapy for patients with sickle disease (SCD), but pose significant clinical challenges. Guidance specific indications and administration transfusion, as well screening, prevention, management alloimmunization, delayed hemolytic transfusion reactions (DHTRs), iron overload may improve outcomes.Our objective was to develop evidence-based guidelines support patients, clinicians, other healthcare professionals in their decisions about SCD the...
Sickle cell disease is characterized by the painful recurrence of vaso-occlusive events. Gene therapy with use LentiGlobin for sickle (bb1111; lovotibeglogene autotemcel) consists autologous transplantation hematopoietic stem and progenitor cells transduced BB305 lentiviral vector encoding a modified β-globin gene, which produces an antisickling hemoglobin, HbAT87Q.
Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent β-thalassemia contains autologous CD34+ hematopoietic stem cells and progenitor transduced with the BB305 lentiviral vector encoding β-globin (βA-T87Q) gene.In this open-label, phase 3 study, we evaluated efficacy safety of beti-cel in adult pediatric patients a non-β0/β0 genotype. Patients underwent myeloablation busulfan (with doses adjusted on basis pharmacokinetic analysis) received intravenously. The primary end...
BackgroundExagamglogene autotemcel (exa-cel) is a nonviral cell therapy designed to reactivate fetal hemoglobin synthesis through ex vivo clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 gene editing of the erythroid-specific enhancer region BCL11A in autologous CD34+ hematopoietic stem and progenitor cells (HSPCs).MethodsWe conducted an open-label, single-group, phase 3 study exa-cel patients 12 35 years age with transfusion-dependent β-thalassemia β0/β0, β0/β0-like,...
Abstract Objectives/methods: This 1‐yr prospective phase II trial evaluated the efficacy of deferasirox in regularly transfused patients aged 3–81 yrs with myelodysplastic syndromes (MDS; n = 47), Diamond–Blackfan anaemia (DBA; 30), other rare anaemias ( 22) or β‐thalassaemia 85). Dosage was determined by baseline liver iron concentration (LIC). Results: In LIC ≥7 mg Fe/g dry weight, initiated at 20 30 mg/kg/d produced statistically significant decreases P < 0.001); these were greatest...
Adults with beta thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence pain in all syndromes childhood, adolescence, adulthood, associations BMD fractures pain, etiology disease thalassemia. Patients Thalassemia Clinical Research Network, > or =6 yr age, no preexisting medical condition affecting mass requiring steroids, participated. We measured spine femur whole body BMC by DXA assessed vertebral abnormalities...
Silent infarcts have been reported most commonly in school-aged children with homozygous sickle cell disease (SCD-SS) and are associated neurocognitive deficits. However, the prevalence of silent younger SCD-SS is not well defined. In this retrospective study, brain magnetic resonance imaging angiography (MRI/A) studies performed before 6 years age a cohort were analysed abnormalities was calculated. Clinical laboratory parameters compared between groups without infarcts. Sixty-eight 96 had...
This study aimed to determine differences in the rates of growth, endocrine- and calcium-related abnormalities various thalassemia syndromes North America treated with current therapies. Medical history, physical examinations blood urine collections were obtained from patients all age 6 years older Thalassemia Clinical Research Network. 361 subjects, 49% male, mean 23.2 (range 6.1-75 years) studied. Approximately 25% children adults, regardless syndrome, had short stature. Overall growth was...
Pyruvate kinase deficiency is caused by mutations in PKLR and leads to congenital hemolytic anemia. Mitapivat an oral, small-molecule allosteric activator of pyruvate red cells.In this uncontrolled, phase 2 study, we evaluated the safety efficacy mitapivat 52 adults with who were not receiving red-cell transfusions. The patients randomly assigned receive either 50 mg or 300 twice daily for a 24-week core period; eligible could continue treatment ongoing extension phase.Common adverse events,...
Summary Red blood cell (RBC) transfusion is the primary treatment for severe forms of thalassaemia. Pre‐storage screening has resulted in decreased transfusion‐transmitted infections, but anti‐RBC antibodies remain a major problem. We report on 697 participants who had ever received transfusions. Allo‐ and autoantibody rates were compared with respect to splenectomy status, ethnicity, diagnosis, duration transfusions, centre, age at initiation, together before after 1990, when leucoreduction...
Summary Little is known about the effects of thalassaemia on kidney. Characterization underlying renal function abnormalities in timely because newer iron chelator, deferasirox, can be nephrotoxic. We aimed to determine prevalence and correlates patients, treated before deferasirox was widely available, using 24‐h collections urine. calculated creatinine clearance urine calcium‐to‐creatinine ratio measured urinary β 2 ‐microglobulin, albumin, protein. used multivariate modelling identify...
Although hemoglobin SC (HbSC) disease is usually considered less severe than sickle cell anemia (SCA), which includes HbSS and HbS/β 0 ‐thalassemia genotypes, many patients with HbSC experience complications, including vaso‐occlusive pain, acute chest syndrome, avascular necrosis, retinopathy, poor quality of life. Fully 20 years after the clinical laboratory efficacy hydroxyurea was proven in adult SCA patients, safety utility treatment for remain unclear. Recent NHLBI evidence‐based...