Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established curative approach for a variety of malignant and nonmalignant hematologic disorders. Disease relapse, graft versus host disease (GVHD), infection, and regimen related toxicity remain the primary causes of transplant failure. The tempo and quality of hematopoietic engraftment and immune reconstitution significantly influence post-HSCT morbidity and mortality. Adult recipients of an allo-HSCT experience deficiencies in their B and T cell reconstitution, which can persist for over a year, and are associated with an Increased risk of infection, relapse, and secondary malignancies. Delayed reconstitution of CD4 T cells, associated with advanced patient age, HLA disparity, and method of prevention of GVHD and graft rejection, correlates with an increased risk of fatal opportunistic infections. Despite the increased use of molecular typing of HLA alleles for more stringent matching of patient and unrelated donors, and intensified regimens to prevent and treat invasive viral, fungal, and parasitic infections, opportunistic infections represent the primary cause of death in most unrelated transplant series, regardless of the stem cell source (bone marrow, peripheral blood, or cord blood), and irrespective ofthe use of T cell depletion. The clinical trials and research projects outlined in this grant are designed to test transplant approaches, biologicals and cell therapies to accelerate full functional recovery of the hematopoietic and immune systems and provide immune T-cells to eradicate viral infections and enhance resistance to leukemia in recipients of allo-HSCT. The purpose of Core A is to define hematopoietic cell grafts and adoptively transferred T-cells and their function prior to and following HSCT. Core A will characterize allografts and monitor the effects of stem cell source, donor type, use of T cell depletion, immunomodulatory agents, such as KGF or androgen blockade, and/ or adoptive immunotherapy, as well as development of GVHD on the kinetics and quality of immune reconstitution, donor chimerism, and minimal residual disease. Core A will also centralize specimen procurement and provide a centralized storage repository.

Public Health Relevance

Over the last 20 years, this core facility has been responsible for performing phenotype, function, detection of minimal residual disease, and lineage specific chimerism in patients undergoing allo-HSCT on clinical trials at MSKCC. A detailed analysis of stem cell grafts and adoptively transferred T cells as well as immune monitoring in recipients of these cellular products is critical to our understanding of how these interventions can decrease morbidity and mortality and improve outcomes

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York
United States
Zip Code
Dao, Tao; Korontsvit, Tatyana; Zakhaleva, Victoria et al. (2017) An immunogenic WT1-derived peptide that induces T cell response in the context of HLA-A*02:01 and HLA-A*24:02 molecules. Oncoimmunology 6:e1252895
Peled, Jonathan U; Devlin, Sean M; Staffas, Anna et al. (2017) Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation. J Clin Oncol 35:1650-1659
Getta, Bartlomiej M; Roshal, Mikhail; Zheng, Junting et al. (2017) Allogeneic Hematopoietic Stem Cell Transplantation with Myeloablative Conditioning Is Associated with Favorable Outcomes in Mixed Phenotype Acute Leukemia. Biol Blood Marrow Transplant 23:1879-1886
Barba, Pere; Ratan, Ravin; Cho, Christina et al. (2017) Hematopoietic Cell Transplantation Comorbidity Index Predicts Outcomes in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Receiving CD34+ Selected Grafts for Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 23:67-74
Barba, Pere; Hilden, Patrick; Devlin, Sean M et al. (2017) Ex Vivo CD34+-Selected T Cell-Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease Biol Blood Marrow Transplant 23:452-458
Boudreau, Jeanette E; Giglio, Fabio; Gooley, Ted A et al. (2017) KIR3DL1/ HL A-B Subtypes Govern Acute Myelogenous Leukemia Relapse After Hematopoietic Cell Transplantation. J Clin Oncol 35:2268-2278
Ghosh, Arnab; Smith, Melody; James, Scott E et al. (2017) Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity. Nat Med 23:242-249
Fischer, Julius C; Bscheider, Michael; Eisenkolb, Gabriel et al. (2017) RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury. Sci Transl Med 9:
Goldberg, Jenna D; Zheng, Junting; Ratan, Ravin et al. (2017) Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant. Leuk Lymphoma 58:1859-1871
Ito, Reiko; Hale, Laura P; Geyer, Susan M et al. (2017) Late Effects of Exposure to Ionizing Radiation and Age on Human Thymus Morphology and Function. Radiat Res 187:589-598

Showing the most recent 10 out of 435 publications