Susan E. Prockop
- Hematopoietic Stem Cell Transplantation
- Cytomegalovirus and herpesvirus research
- Viral-associated cancers and disorders
- CAR-T cell therapy research
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- Polyomavirus and related diseases
- Immunodeficiency and Autoimmune Disorders
- Virus-based gene therapy research
- Lymphoma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Chronic Lymphocytic Leukemia Research
- T-cell and B-cell Immunology
- Renal Transplantation Outcomes and Treatments
- Herpesvirus Infections and Treatments
- Parvovirus B19 Infection Studies
- Mesenchymal stem cell research
- Childhood Cancer Survivors' Quality of Life
- Autoimmune and Inflammatory Disorders Research
- Transplantation: Methods and Outcomes
- CNS Lymphoma Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Neonatal Respiratory Health Research
- Immunotherapy and Immune Responses
- Blood disorders and treatments
Boston Children's Hospital
2022-2025
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2022-2025
Boston Children's Museum
2024-2025
Memorial Sloan Kettering Cancer Center
2015-2024
Harvard University
2022-2024
Dana-Farber Cancer Institute
2022-2024
Center for Cancer and Blood Disorders
2023-2024
Cornell University
2012-2022
Weill Cornell Medicine
2021-2022
MedStar Georgetown University Hospital
2022
Cellular differentiation is a complex process involving integrated signals for lineage specification, proliferation, endowment of functional capacity, and survival or cell death. During embryogenesis, spatially discrete environments regulating these processes are established during the growth tissue mass, that also results in temporal separation developmental events. In tissues undergo steady-state postnatal differentiation, another means inducing spatial cues must be established. Here we...
Chimeric antigen receptor (CAR) T cells have demonstrated clinical benefit in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We undertook a multicenter trial to determine toxicity, feasibility, and response for this therapy. A total of 25 pediatric/young adult (age, 1-22.5 years) R/R B-ALL were treated 19-28z CAR cells. Conditioning chemotherapy included high-dose (3 g/m2) cyclophosphamide (HD-Cy) 17 low-dose (≤1.5 (LD-Cy) 8 patients. Fifteen had...
Severe steroid-refractory acute graft-versus-host disease (aGVHD) is related to significant mortality and morbidity after allogeneic stem cell transplantation. Early clinical trials of therapy with human mesenchymal cells (hMSCs) in pediatric patients severe aGVHD resistant multiple immunosuppressive agents showed promising results. In this study, we evaluated the risk/benefit profile remestemcel-L (Prochymal), a third-party, off-the-shelf source hMSCs, as rescue agent for...
BACKGROUND. Adoptive transfer of donor-derived EBV-specific cytotoxic T-lymphocytes (EBV-CTLs) can eradicate EBV-associated lymphomas (EBV-PTLD) after transplantation hematopoietic cell (HCT) or solid organ (SOT) but is unavailable for most patients.
Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications transplantation, availability alternative donor sources, less toxic preparative regimens, new manipulation techniques, novel GVHD prevention methods, all which have expanded the applicability procedure. These advances led to clinical practice conundrums when...
Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to large group of RAG-mutated patients, we aimed at characterizing the immunopathology associated each phenotype. Although defective T B cell development is common all phenotypes, patients hypomorphic RAG variants generate cells signatures immune dysregulation produce autoantibodies broad range self-antigens, including type I interferons....
Abstract T cell differentiation in the thymus depends on sequential interactions between lymphoid progenitors and stromal cells discrete regions of cortex. Here we show that CXCL12/CXCR4 signaling is absolutely required for proper localization early into cortex thus successful steady state differentiation. All express CXCR4, its ligand (CXCL12) expressed only by cortex, where are found. Early migrate response to CXCL12 vitro, while thymus-specific deletion CXCR4 vivo results failed cortical...
Abstract Thymic T cell production is characterized by differentiating waves of non-self-renewing, bone marrow-derived progenitors. The factors constraining new progenitor recruitment, intrathymic precursor expansion, and thymus size remain enigmatic, but are believed to be controlled a feedback loop responding lymphoid cellularity competition for stromal niches. In this study, we show that niches does occur, solely limited cells at the early CD4−8− stages differentiation. overall organ...
Steroid-refractory acute graft-versus-host disease (SR-aGVHD) following hematopoietic cell transplantation (HSCT) is associated with poor clinical outcomes. Currently, there are no safe and effective therapies approved for use in the pediatric population under age of 12 years. Accordingly, an urgent need new treatments that safe, well tolerated, managing this debilitating potentially fatal complication HSCT. In early phase trials, mesenchymal stromal cells (MSCs) have demonstrated efficacy...
BACKGROUND. Refractory CMV viremia and disease are associated with significant morbidity mortality in recipients of hematopoietic stem cell transplant (HCT).
Patients with Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disease (EBV+ PTLD) in whom initial treatment fails have few options and historically low median overall survival (OS) of 0.7 months after allogeneic hematopoietic cell transplant (HCT) 4.1 solid organ (SOT). Tabelecleucel is an off-the-shelf, EBV-specific cytotoxic T-lymphocyte immunotherapy for EBV+ PTLD. Previous single-center experience showed responses patients PTLD HCT or SOT. We now report outcomes from...
Despite clinical benefit with the use of CAR T-cells, need to manufacture patient-specific products severely limits utility this therapy. To overcome barrier, we developed an allogeneic, "off-the-shelf" T-cell product using Epstein-Barr virus (EBV)-specific T cells (EBV-VSTs) genetically modified a CD19-specific (19-28z). Patients relapsed/refractory (R/R) B-cell malignancies (n=16) were stratified into 3 treatment cohorts: cohort 1 (n=8; disease recurrence after allogeneic or autologous...
Highlights-Adoptive transfer of donor-derived cytomegalovirus cytotoxic T cells for persisting viremia.-CMVpp65-specific sensitized with 15-mers peptides spanning CMVpp65 are safe and effective.-CMVpp65-specific exhibit specificity 1 to 3 epitopes presented class I II HLA alleles.AbstractWe conducted a phase trial allogeneic in vitro against pool pentadecapeptides (15-mer peptides) the sequence adoptive therapy 17 hematopoietic cell transplant recipients (CMV) viremia or clinical infection...
Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated diminished and exaggerated responses. Management these patients is complicated; oftentimes immunosuppressive therapies insufficient, may require hematopoietic transplant (HCT) for treatment. Analysis HCT data have previously focused on a single defect. This...
Clinical outcomes in children with steroid-refractory acute graft-versus-host disease (SR-aGVHD) are generally poor, a high mortality rate and limited therapeutic options. Here we report our updated investigational experience mesenchymal stromal cell (MSC) therapy remestemcel-L multicenter expanded access protocol (ClinicalTrials.gov identifier NCT00759018) 241 aGVHD who failed to respond steroids or without other secondary tertiary immunosuppressive therapies. A total of grade B-D SR-aGVHD...