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Blood and Marrow Transplant
A photo of the 2010 Behavioral Science Core

2011 Blood and Marrow Transplant Section

Transplantation of hematopoietic stem cells derived from bone marrow or peripheral blood following chemotherapy or radiation has been used as a treatment for high-risk cancers for four decades.  For children with leukemia who relapse or who are at high risk for relapse, blood or marrow transplantation (BMT) from another individual (allogeneic) can result in cure in approximately 50% patients.  Although initially performed as a rescue after very high doses of cytotoxic therapy, it is now evident that the donor immune system contributes to the curative potential allogeneic BMT (known as the graft versus tumor reaction).  Unfortunately, when this reaction targets normal tissues (graft versus host disease) serious side effects (including mortality) occur.  The primary focus of the Blood and Marrow Transplant Section of the Pediatric Oncology Branch is to develop approaches to increase the curative potential and minimize the toxicity associated with BMT.  The projects in the laboratory fall into two broad categories:

I.  Increasing the specificity of the graft versus tumor reaction. The primary  cells in the donor immune system that mediate the graft versus tumor reaction  are lymphocytes (T cells and natural killer cells). Ongoing studies in the BMT section are  exploring methods to educate these cells to recognize targets that are  expressed exclusively or to a greater degree on tumor cells compared to normal  tissues as a means of increasing the specificity and potency of the donor  immune response against the tumor. 

II. Minimizing graft versus host disease. Current standard  methods to prevent graft versus host disease (GVHD) involve the administration of immune suppressive agents. While these can be effective, they can also  increase the risk of infection and relapse. Dendritic cells are specialized cells responsible for orchestrating  immune responses and have been shown to play an important role in the development  of GVHD.  We have identified that selectively  targeting cytokine pathways (Interferon gamma) in donor-derived antigen  presenting cells can prevent GVHD. Importantly, in these transplants, the function of lymphocytes appears  to remain intact potentially preserving the opportunity to generate immune  responses against infections or cancer. Ongoing work is assessing how these principles might be translated into clinical trials.

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