We are developing an MHC-haploidentical allogeneic bone marrow transplantation model that parallels human treatment and can be used to decipher the immunologic impact of post-transplantation cyclophosphamide (PTCy). We are studying the impact of this therapy on clinical endpoints (survival, graft-versus-host disease, weight); accompanying these studies is a detailed characterization of the immunologic and histopathologic changes associated with this approach. Once the model is fully characterized and the mechanisms by which PTCy prevents GVHD uncovered, we will use this understanding as a basis to explore how to refine this BMT approach clinically towards the clinical goals of further reducing graft-versus-host disease, ensuring reliable engraftment with minimal conditioning, and serving as a platform for other therapies to reduce relapse. We also are exploring the impact of PTCy on human T cells in mixed lymphocyte cultures with the goal of improving our understanding of the immunologic impact of PTCy in order to improve clinical outcomes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011659-03
Application #
9556662
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Kanakry, Christopher G; Luznik, Leo (2018) Teaching a Young Dog New Tricks: Modifications to the Post-Transplantation Cyclophosphamide Haploidentical Transplantation Platform. Biol Blood Marrow Transplant 24:1108-1110
Kanakry, Christopher G; Coffey, David G; Towlerton, Andrea M H et al. (2016) Origin and evolution of the T cell repertoire after posttransplantation cyclophosphamide. JCI Insight 1:
Kanakry, Christopher G; Fuchs, Ephraim J; Luznik, Leo (2016) Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol 13:10-24
Kanakry, Christopher G; O'Donnell, Paul V; Furlong, Terry et al. (2014) Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol 32:3497-505
Kanakry, Christopher G; Tsai, Hua-Ling; BolaƱos-Meade, Javier et al. (2014) Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS. Blood 124:3817-27