A5033913868- Hematopoietic Stem Cell Transplantation
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Virus-based gene therapy research
- Acute Myeloid Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- RNA Interference and Gene Delivery
- Childhood Cancer Survivors' Quality of Life
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Renal Transplantation Outcomes and Treatments
- Polyomavirus and related diseases
- Neonatal Health and Biochemistry
- Nutritional Studies and Diet
- Toxoplasma gondii Research Studies
- Immune responses and vaccinations
- Blood groups and transfusion
- CRISPR and Genetic Engineering
- Herpesvirus Infections and Treatments
- Synthesis and Properties of Aromatic Compounds
- Inflammatory Biomarkers in Disease Prognosis
- Rabies epidemiology and control
- Microtubule and mitosis dynamics
- Pneumocystis jirovecii pneumonia detection and treatment
St. Jude Children's Research Hospital
2015-2024
University of Tennessee Health Science Center
2017-2023
Children's Research Hospital
2020
Children's National
2012-2019
National Heart Lung and Blood Institute
2014
National Institutes of Health
2014
Allogeneic hematopoietic stem-cell transplantation for X-linked severe combined immunodeficiency (SCID-X1) often fails to reconstitute immunity associated with T cells, B and natural killer (NK) cells when matched sibling donors are unavailable unless high-dose chemotherapy is given. In previous studies, autologous gene therapy γ-retroviral vectors failed B-cell NK-cell was complicated by vector-related leukemia.We performed a dual-center, phase 1-2 safety efficacy study of lentiviral vector...
Abstract Background T‐cell depletion ( TCD ) effectively reduces severe graft‐versus‐host disease in recipients of HLA ‐mismatched allografts. However, is associated with delayed immune recovery and increased infections. We hypothesized that specific CD 45 RA + naive T cells, rather than broad 3+ can preserve memory‐immunity the allografts confer protection against important viral infections early post‐transplant period. Methods Sixty‐seven patients who received haploidentical donor...
Abstract Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral prior studies. We performed phase II multicenter study (NCT03475212) the patients with inborn errors immunity and/or post allogeneic hematopoietic stem transplant using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, clinical...
The treatment of pediatric high-risk neuroblastoma is intensive and multimodal. Despite the introduction immunotherapy for minimal residual disease, survival rates remain suboptimal new therapies are needed. As part a phase 2 trial, we using consolidation therapy regimen that combines busulfan/melphalan conditioning schema, autologous hematopoietic cell transplantation (AHCT), experimental with hu14.18K322A (a humanized anti-GD2 monoclonal antibody), granulocyte-macrophage colony-stimulating...
Summary The effects of reduced intensity conditioning (RIC) on human leucocyte antigen (HLA)‐alloimmunization and platelet transfusion refractoriness (PTR) following allogeneic haematopoietic stem cell transplantation (Allo‐HSCT) are unknown. We studied HLA‐alloantibodies in a cohort 16 patients (eight HLA‐alloimmunized with pre‐transplant histories PTR eight non‐alloimmunized controls) undergoing Allo‐HSCT using fludarabine/cyclophosphamide‐based RIC. Pre‐ post‐transplant serum samples were...
Abstract Background Relapse remains a challenge after transplantation in pediatric patients with hematological malignancies. Myeloablative regimens used for disease control are associated acute and long-term adverse effects. We CD45RA-depleted haploidentical graft adoptive transfer of memory T cells combined NK-cell addback hypothesized that maximizing the graft-versus-leukemia (GVL) effect might allow reduction intensity conditioning regimen. Methods In this phase II clinical trial...
Development of a diverse T-cell receptor β (TRB) repertoire is associated with immune recovery following hematopoietic cell transplantation (HCT) for severe combined immunodeficiency (SCID). High-throughput sequencing the TRB allows evaluation clonotype dynamics during reconstitution.
Abstract Pediatric and adolescent young adult (AYA) patients who receive many blood product transfusions, such as individuals with sickle cell disease (SCD), severe aplastic anemia (SAA) or indolent hematologic malignancies, are at high risk for developing donor‐specific antibodies (DSA). DSAs mean fluorescence intensity (MFI) greater than 5000 have been associated significant graft failure, but lower MFI values between 2000 may result in poor function after hematopoietic transplant (HCT)....
Lentiviral vector (LV)–based gene therapy holds promise for a broad range of diseases. Analyzing more than 280,000 integration sites (VISs) in 273 samples from 10 patients with X-linked severe combined immunodeficiency (SCID-X1), we discovered shared LV integrome signatures 9 relation to the genomics, epigenomics, and 3D structure human genome. VISs were enriched nuclear subcompartment A1 integrated into super-enhancers close pore complexes. These validated T cells transduced an encoding...
Abstract Secondary hemophagocytic syndrome (HPS) has been described after autologous hematopoietic cell transplant (AutoHCT). We report two cases of secondary HPS novel consolidation therapy for high‐risk neuroblastoma as part an institutional phase 2 trial incorporating immunotherapy into a “standard” AutoHCT regimen. Both patients developed liver dysfunction beyond expected course hepatic veno‐occlusive disease, coagulopathy, hyperferritinemia, and when evaluated, elevated soluble...
IntroductionDonor T-cell reconstitution following hematopoietic cell transplantation (HCT) is critical for infection and leukemic control. Donor lymphocyte infusions (DLI) provide additional donor T cells, but may cause graft-versus-host-disease (GVHD) from alloreactive T-cells. As GVHD risk increases with increasing HLA-mismatch, conventional haploidentical DLI doses are often limited to 1 × 105 cells/kg. Since the majority of cells reside in naïve (CD45RA-positive) subset, CD45RA-depleted...
Patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplantation (HCT) have a poor prognosis. Although proceeding to subsequent HCT can provide potential for long-term survival, there are limited data guide which patients most likely benefit and strategies best in this heavily pretreated population. The goals of study were describe the clinical outcomes pediatric relapsed cohort enriched haploidentical donors, evaluate associations patient-, disease-,...