The incidence of post transplant complications, such as graft failure, disease recurrence, and infection, depend not only on host factors and the cytoreduction employed, but also on characteristics of the graft which impact on its ability to give rise to full and durable donor chimerism, hematopoesis, and reconstitution of the immune system. The biological significance of minor genetic disparities between donor and host detected by Class I and Class II DNA typing, or the abnormal immune studies documented in vitro in patients post transplant is suggested by the increased incidence of graft rejection, severe graft versus host disease, and fatal infectious complications, particularly in adults following unmodified, partially T cell depleted, or fully TCD unrelated marrow transplantation. Investigation of the mechanisms underlying resistance to engraftment, disease recurrence, and susceptibility to infection, and the clinical strategies designed to overcome them form the basis of this program project. It is therefore the aim of this core project to provide a centralized program to monitor the effect of stem cell source and its subsequent manipulation on the quality of the graft infused, donor/host chimerism, and immune reconstitution. The stem cell transplants will be analyzed for degree and quality of T-cell depletion, nucleated and CD34+ cell dose, and hematopoetic progenitor cell content. The regenerating marrow and circulating lymphoid cells will be assessed for lineage specific chimerism by ministatelite PCR analysis. The phenotype, antigen-specific and non-specific proliferation, cytotoxicty, and cytokine production of the circulating lymphoid populations will be longitudinally evaluated. These studies will provide an analysis to gauge the effects of stem cell source (marrow, peripheral blood, cord blood), degree of histoincompatibility, alternative methods of cytoreduction, T-cell depletion, graft rejection prophylaxis, and adoptive immunotherapy on engraftment, disease eradication, and the redeveloping immune system.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Sloan-Kettering Institute for Cancer Research
New York
United States
Zip Code
Boudreau, Jeanette E; Hsu, Katharine C (2018) Natural Killer Cell Education and the Response to Infection and Cancer Therapy: Stay Tuned. Trends Immunol 39:222-239
Lin, Richard J; Ho, Caleb; Hilden, Patrick D et al. (2018) Allogeneic haematopoietic cell transplantation impacts on outcomes of mantle cell lymphoma with TP53 alterations. Br J Haematol :
Malard, Florent; Labopin, Myriam; Cho, Christina et al. (2018) Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC. J Hematol Oncol 11:127
Luduec, Jean-BenoƮt Le; Kudva, Anupa; Boudreau, Jeanette E et al. (2018) Novel multiplex PCR-SSP method for centromeric KIR allele discrimination. Sci Rep 8:14853
Shah, Gunjan L; Moskowitz, Craig H (2018) Transplant strategies in relapsed/refractory Hodgkin lymphoma. Blood 131:1689-1697
Avanzi, Mauro P; Yeku, Oladapo; Li, Xinghuo et al. (2018) Engineered Tumor-Targeted T Cells Mediate Enhanced Anti-Tumor Efficacy Both Directly and through Activation of the Endogenous Immune System. Cell Rep 23:2130-2141
Staffas, Anna; Burgos da Silva, Marina; Slingerland, Ann E et al. (2018) Nutritional Support from the Intestinal Microbiota Improves Hematopoietic Reconstitution after Bone Marrow Transplantation in Mice. Cell Host Microbe 23:447-457.e4
Velardi, Enrico; Tsai, Jennifer J; Radtke, Stefan et al. (2018) Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury. Nat Med 24:239-246
Moskowitz, Craig H (2018) Should all patients with HL who relapse after ASCT be considered for allogeneic SCT? A consult, yes; a transplant, not necessarily. Blood Adv 2:821-824
Kim, Seong Jin; Huang, Yao-Ting; Foldi, Julia et al. (2018) Cytomegalovirus resistance in CD34+ -selected hematopoietic cell transplant recipients. Transpl Infect Dis 20:e12881

Showing the most recent 10 out of 452 publications