A5081766444- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Acute Lymphoblastic Leukemia research
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Acute Myeloid Leukemia Research
- Childhood Cancer Survivors' Quality of Life
- Hemoglobinopathies and Related Disorders
- Developmental Biology and Gene Regulation
- Hepatitis B Virus Studies
- Immunodeficiency and Autoimmune Disorders
- Prenatal Screening and Diagnostics
- Zebrafish Biomedical Research Applications
- Polyomavirus and related diseases
- Hepatitis C virus research
- RNA Interference and Gene Delivery
- Mesenchymal stem cell research
- Cytomegalovirus and herpesvirus research
- Chronic Myeloid Leukemia Treatments
- Epigenetics and DNA Methylation
- Blood disorders and treatments
- Biopolymer Synthesis and Applications
- Neuroblastoma Research and Treatments
- Ethics and Legal Issues in Pediatric Healthcare
Rainbow Babies & Children's Hospital
2018-2025
University Hospitals Seidman Cancer Center
2020-2025
Cancer Institute (WIA)
2020-2025
Cleveland Clinic
2020-2025
Case Western Reserve University
2019-2024
St. Jude Children's Research Hospital
2010-2019
University School
2019
University of Tennessee Health Science Center
2011-2016
Fred Hutch Cancer Center
2004-2008
University of Washington
2005-2007
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Advancements in technology that enhance our understanding of biology disease, risk-adapted therapy, and enhanced supportive care have contributed to improved survival rates. However, additional clinical management needed improve outcomes for patients classified as high risk at presentation (eg, T-ALL, infant ALL) who experience relapse. The NCCN Clinical Practice Guidelines Oncology (NCCN Guidelines) ALL provide...
HLA-matched related donor (MRD) hematopoietic stem cell transplantation (HSCT) is a well-established therapy for patients with sickle disease (SCD); however, experience using alternative donors, including haploidentical in HSCT SCD limited. We report the long-term outcomes of 22 pediatric who underwent at St. Jude Children's Research Hospital, either myeloablative sibling MRD (n = 14) or reduced-intensity parental 8). The median patient age was 11.0 ± 3.9 years graft recipients and 9.0 5.0...
After hematopoietic stem cell transplantation (HSCT), successful engraftment and immune recovery is necessary to protect the patient from relapse infection. Many studies highlight importance of conventional αβ T after HSCT, but impact γδ has not been well described. Here, we investigate cells in 102 pediatric patients with acute leukemia first clinical remission who underwent allogeneic HSCT at St. Jude Children's Research Hospital 1996 2011. Mean age was 10.5 ± 5.9 years (range, .6 25.2),...
Pediatric acute lymphoblastic leukemia elicits a broad, functional, antitumor T cell response, targeting multiple mutations.
Notch signaling regulates multiple cell fate decisions by hematopoietic precursors. To address whether different amounts of ligand influence lineage choices, we cultured murine bone marrow lin−Sca-1+c-kit+ cells with increasing densities immobilized Delta1ext-IgG consisting the extracellular domain Delta1 fused to Fc human IgG1. We found that relatively lower enhanced generation Sca-1+c-kit+ cells, Thy1+CD25+ early T precursors, and B220+CD43−/lo that, when cocultured OP9 stroma...
Transgenic expression of antigen-specific T-cell receptor (TCR) genes is a promising approach for immunotherapy against infectious diseases and cancers. A key to the efficient application this rapid specific isolation cloning TCRs. Current methods are often labor-intensive, nonspecific, and/or relatively slow. Here, we describe an system αβTCR CDR3 substitution. We demonstrate capability influenza-specific TCRs within 10 days using single-cell polymerase chain reaction (PCR) Gibson Assembly...
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Acute Lymphoblastic Leukemia (ALL) were developed as a result of meetings convened by multidisciplinary panel pediatric ALL experts, with the goal providing recommendations on standard treatment approaches based current evidence. focus risk assessment and stratification risk-adapted therapy; strategies BCR::ABL1 (Philadelphia chromosome [Ph])-negative -positive B-cell lineage, T-cell infant ALL; supportive care...
Background Novel therapies are needed for children with relapsed or refractory leukemia. We therefore tested the safety and feasibility of haploidentical natural killer cell therapy in this patient population. Procedure Twenty‐nine who had leukemia were treated chemotherapy followed by infusion NK cells. Cohort 1 included 14 not undergone prior allogeneic hematopoietic transplantation (HCT), whereas 2 15 that after HCT. Results Twenty‐six (90%) donors KIR mismatched (14 one 12 KIRs). The...
Donor lymphocyte infusion (DLI) is commonly used to treat leukemia relapse following stem cell transplantation. In florid relapse, however, the efficacy of DLI limited with substantial risk severe graft-versus-host disease (GvHD). Here, we develop a novel risk-adapted strategy characterized by pre-emptive initiated at time mixed chimerism, small starting dose based on donor source, dose-escalation guided real-time chimerism monitoring and withholding immediately in patients achieving full...
Rate of immune reconstitution directly correlates with the number hematopoietic stem cells infused and is particularly delayed in patients undergoing cord blood (CB) transplantation (CBT). Methods to increase CB natural killer (NK) have potential improve after CBT. NK are first lymphocyte population recover central preventing early relapse infection. low known be incomplete maturation require activation for effective function. Here, we report a clinically relevant ex vivo expansion method...
T-cell malignancies expressing the γδ receptor (TCR) are often associated with poor prognosis. Here, we determined clinical outcome of pediatric patients acute lymphoblastic leukemia (T-ALL) TCR. Of 100 newly diagnosed T-ALL patients, 93 had TCR analysis performed at diagnosis. Repertoire was evaluated by paired sequencing rearranged All received intensified chemotherapy and those minimal residual disease (MRD) ≥ 1% on day 42–46 became candidates for hematopoietic cell transplantation. 12...
Daratumumab, a CD38 monoclonal antibody that has been FDA-approved to treat multiple myeloma, acquired popularity and is used off-label for both auto- alloantibody mediated disorders, particularly in refractory/resistant circumstances. Much of the published data its use pediatric blood disorders post-transplant autoimmune cytopenias. Here we describe three patients whom daratumumab was outside cytopenias, highlighting further potential uses this medication.
The safety, pharmacokinetics, and biological effect of plerixafor in children as part a conditioning regimen for chemo-sensitization allogeneic hematopoietic stem cell transplantation (HSCT) have not been studied. This is phase I study designed to evaluate its tolerability at dose .24 mg/kg given intravenously on day -4 (level 1); -3 2); or -4, -3, -2 3) combination with fludarabine, thiotepa, melphalan, rabbit antithymocytic globulin second HSCT refractory relapsed leukemia. Immunophenotype...
Pillai A, Hartford C, Wang Pei D, Yang J, Srinivasan Triplett B, Dallas M, Leung W. Favorable preliminary results using TLI/ATG‐based immunomodulatory conditioning for matched unrelated donor allogeneic hematopoietic stem cell transplantation in pediatric severe aplastic anemia. Pediatr Transplantation 2011: 15: 628–634. © 2011 John Wiley & Sons A/S. Abstract: To assess whether a tolerance‐induction regimen could be applied (MUD) HCT SAA, we retrospectively reviewed our experience...
This study analyzes the hematopoietic cell transplantation experience in patients with immune deficiency at a single institution. The objective is to comprehensively evaluate short-term and long-term outcomes various preparative regimens, donor grafts, ex vivo manipulations identify approaches that most likely favor early competency without generating excessive toxicity. Clinical were evaluated 52 consecutive deficiencies. Thirty-seven of (71%) survived attenuation their underlying disease....
Children with relapsed or refractory solid tumors face dismal prognoses, and novel therapies are desperately needed. Allogeneic hematopoietic cell transplantation (HCT) offers potential for cell-based therapy, but the toxicity of myeloablation limits this approach in heavily pretreated patients. We sought to determine feasibility HCT a cohort 24 children incurable using human leukocyte antigen-matched sibling unrelated donors minimal conditioning regimen. Before stem infusion, all patients...
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-,...