A5012557553- CAR-T cell therapy research
- Acute Lymphoblastic Leukemia research
- Childhood Cancer Survivors' Quality of Life
- Hematopoietic Stem Cell Transplantation
- Neutropenia and Cancer Infections
- Hemoglobinopathies and Related Disorders
- Advancements in Semiconductor Devices and Circuit Design
- Immunodeficiency and Autoimmune Disorders
- Neuroblastoma Research and Treatments
- Virus-based gene therapy research
- Safe Handling of Antineoplastic Drugs
- Blood disorders and treatments
- Global Cancer Incidence and Screening
- Estrogen and related hormone effects
- Glioma Diagnosis and Treatment
- Cytomegalovirus and herpesvirus research
- NF-κB Signaling Pathways
- Pharmacogenetics and Drug Metabolism
- Folate and B Vitamins Research
- Chronic Lymphocytic Leukemia Research
- Optimism, Hope, and Well-being
- Glutathione Transferases and Polymorphisms
- Grief, Bereavement, and Mental Health
- BRCA gene mutations in cancer
- Immune Cell Function and Interaction
Children's Hospital of Philadelphia
2005-2025
University of Pennsylvania
2005-2025
Philadelphia University
2024
Pediatrics and Genetics
2021
Dupont Hospital
2018
Alfred I. duPont Hospital for Children
2015
DuPont (United States)
2015
Abramson Cancer Center
2005
Family Research Institute
2005
Breast Center
2005
PURPOSE To prospectively evaluate the effectiveness of risk-adapted preemptive tocilizumab (PT) administration in preventing severe cytokine release syndrome (CRS) after CTL019, a CD19 chimeric antigen receptor T-cell therapy. METHODS Children and young adults with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia were assigned to high- (≥ 40%) low- (< tumor burden cohorts (HTBC LTBC) based on bone marrow aspirate biopsy before infusion. HTBC patients received single...
PURPOSE CD19-targeted chimeric antigen receptor (CAR)–modified T cells demonstrate unprecedented responses in B-cell acute lymphoblastic leukemia (B-ALL); however, relapse remains a substantial challenge. Short CAR T-cell persistence contributes to this risk; therefore, strategies improve are needed. METHODS We conducted pilot clinical trial of humanized CD19 product (huCART19) children and young adults with relapsed or refractory B-ALL (n = 72) B-lymphoblastic lymphoma 2), treated two...
Relapse after CD19-directed chimeric antigen receptor (CAR)-modified T cells remains a substantial challenge. Short CAR T-cell persistence contributes to relapse risk, necessitating novel approaches prolong durability. reinfusion (CARTr) represents potential strategy reduce the risk of or treat relapsed disease initial infusion (CARTi). We conducted retrospective review murine (CTL019) humanized (huCART19) anti-CD19/4-1BB across 3 clinical trials commercial tisagenlecleucel for prevention...
Adjuvant chemotherapy cures only a subset of women with nonmetastatic breast cancer. Genotypes in drug-metabolizing enzymes, including functional polymorphisms cytochrome P450 (CYP) and glutathione S-transferases (GST), may predict treatment-related outcomes.We examined CYP3A4*1B, CYP3A5*3, deletions GST mu (GSTM1) theta (GSTT1), as well priori-defined combinations these genes. Using cohort 90 node-positive cancer patients who received anthracycline-based adjuvant followed by high-dose...
Background Relapse of B-cell acute lymphoblastic leukemia (B-ALL) with CD19-antigen loss after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has a dismal prognosis. Novel immunotherapeutic strategies for this patient population are urgently needed. Methods We tested novel, fully human anti-CD22/4-1BB CAR construct, CART22-65s, in parallel phase I studies pediatric and adult B-ALL. After lymphodepletion, CART22-65s was infused using 3-day fractionated dosing scheme, allowing...
10511 Background: CNS relapse of B-ALL is difficult to treat after cranial radiation or multiple relapses. Durable remissions relapsed/refractory (r/r) have been seen with CD19 CAR T cells; however, most trials excluded patients active disease. As we observed trafficking into the CSF, hypothesized that cells could control B-ALL. Methods: We identified children and young adults r/r treated on 4 clinical cells, CTL019 CTL119. NCT01626495 NCT02435849 disease, while former in an amendment as...
BackgroundPatients (pts) receiving CTL019 (tisagenlecleucel) for B-ALL with high tumor burden (HTB) are at risk developing severe CRS. Tocilizumab, an IL-6 receptor antibody, is a vital component of CRS management; however, its role in preventing not known. We sought to determine the effectiveness preemptive tocilizumab (PT) administration decreasing rate grade (gr) 4 HTB pts.MethodsWe conducted pilot trial risk-adapted PT after (NCT02906371). pts, defined as ≥40% bone marrow (BM) blasts...
Unrelated donor (URD) hematopoietic stem cell transplant (HSCT) is associated with an increased risk of severe graft-versus-host disease (GVHD). TCRαβ/CD19 depletion may reduce this risk, whereas maintaining graft-versus-leukemia. Outcome data generally describe haploidentical donors, relatively few URDs. We hypothesized that TCRαβ/CD19-depletion would attenuate the risks GVHD and relapse for URD HSCT. Sixty pediatric young adult (YA) patients hematologic malignancies who lacked a...
Sinusoidal obstruction syndrome is a complication of therapy for pediatric ALL and may be modified by thiopurine methyltransferase activity as well MTHFR genotype. We assessed TPMT *3A, *3B, *3C, C677T A1298C germline genetic polymorphisms among 351 patients enrolled in the thioguanine treatment arm CCG‐1952 clinical trial. genotypes were not associated with SOS risk. The combination variant was These suggest that variation do significantly alter risk exposed to thioguanine. Pediatr Blood...
Severe congenital neutropenia (SCN) is caused by germline mutations, most commonly in
Evaluation of a candidate for hematopoietic cell transplantation (HCT) is complex process with substantial intercenter variability. Although literature providing guidance evaluating the eligibility adults well established, similar children lacking. To address gaps between adult recommendations and specific needs children, we convened panel pediatric HCT experts from wide geographic range American Society Transplantation Cellular Therapy (ASTCT) member institutions to offer pediatric-focused...
Background CART19-related toxicities may require treatment inpatient or in the ICU. We sought to describe inpatient/ICU resource utilization within 30 days of CART19 infusion and evaluate trends from 2012-2019. Methods identified patients (pts) with ALL treated on a clinical trial (NCT01626495, NCT02906371, NCT02374333) commercial product, tisagenlecleucel, at Children's Hospital Philadelphia. Demographic, pharmacy, data were extracted EHR day (d0) d+30 using semi-automated EPIC query tool....