This Program Project Grant seeks continued support for investigations into the biology of hematopoietic cell transplantation (HCT) and the translation of concepts to the clinic to improve the outcomes for patients with serious hematological malignancies. The overarching hypothesis of this proposal is that cellular components are critical to transplantation biology and through the in depth understanding of the molecular and cellular events of discrete cell populations fundamental discoveries will be made which will have critical therapeutic implications. Although our clinical efforts are focused on patients with hematological malignancies the concepts developed have broad implications in many fields of biology and medicine extending to patients with malignancies, autoimmune disorders and undergoing solid organ transplantation. The investigators will focus on the major cellular components of the hematopoietic and immune systems including hematopoietic stem and progenitor cells, B, T, natural killer (NK), NK-T, regulatory and dendritic cell populations. The major events in HCT including stem cell engraftment, graft vs host disease (GVHD), graft vs tumor (GVT) reactions and immune reconstitution will be studied in detail. Clinical studies range from exploratory phase I/I I clinical trials to phase III definitive examinations of treatment strategies. We will build upon our success in the prior funding period where we have developed a novel non-myeloablative preparative regimen which results in consistent donor specific engraftment with maintained GVT effects with markedly reduced risk of GVHD. We will also extend the use of cellular products studied within the context of this Grant and successfully translated to the clinic. The proposal consists of 8 Projects and 4 supportive Cores which provide critical functions of administration, biostatistics and data management, molecular pathology and novel cellular imaging strategies and GMP laboratory services for cell product development and sample distribution. As a whole this integrated group of investigators will focus their efforts on critical issues of hematopoietic cell transplantation and cellular based therapeutics.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (O5))
Program Officer
Merritt, William D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Sen, Nandini; Arvin, Ann M (2016) Dissecting the Molecular Mechanisms of the Tropism of Varicella-Zoster Virus for Human T Cells. J Virol 90:3284-7
Pierini, Antonio; Alvarez, Maite; Negrin, Robert S (2016) NK Cell and CD4+FoxP3+ Regulatory T Cell Based Therapies for Hematopoietic Stem Cell Engraftment. Stem Cells Int 2016:9025835
Khodadoust, M S; Luo, B; Medeiros, B C et al. (2016) Clinical activity of ponatinib in a patient with FGFR1-rearranged mixed-phenotype acute leukemia. Leukemia 30:947-50
Xu, Lian; Hunter, Zachary R; Tsakmaklis, Nicholas et al. (2016) Clonal architecture of CXCR4 WHIM-like mutations in Waldenström Macroglobulinaemia. Br J Haematol 172:735-44
Pierini, Antonio; Strober, William; Moffett, Caitlin et al. (2016) TNF-α priming enhances CD4+FoxP3+ regulatory T-cell suppressive function in murine GVHD prevention and treatment. Blood 128:866-71
Nakasone, Hideki; Sahaf, Bita; Tian, Lu et al. (2016) Presensitization to HY antigens in female donors prior to transplant is not associated with male recipient post-transplant HY antibody development nor with clinical outcomes. Haematologica 101:e30-3
Pierini, Antonio; Colonna, Lucrezia; Alvarez, Maite et al. (2015) Donor Requirements for Regulatory T Cell Suppression of Murine Graft-versus-Host Disease. J Immunol 195:347-55
Ohgami, Robert S; Ma, Lisa; Merker, Jason D et al. (2015) Next-generation sequencing of acute myeloid leukemia identifies the significance of TP53, U2AF1, ASXL1, and TET2 mutations. Mod Pathol 28:706-14
Nakasone, Hideki; Remberger, Mats; Tian, Lu et al. (2015) Risks and benefits of sex-mismatched hematopoietic cell transplantation differ according to conditioning strategy. Haematologica 100:1477-85
Kelley, Todd W; Arber, Daniel A; Gibson, Christine et al. (2015) Template for Reporting Results of Monitoring Tests for Patients With Chronic Myelogenous Leukemia (BCR-ABL1(+)). Arch Pathol Lab Med :

Showing the most recent 10 out of 292 publications