) Whether ex vivo generated hematopoietic cells can provide both short and long-term reconstitution after high dose myeloablative chemotherapy is not known. The ability to generate multipotential hematopoietic cells (HPC) ex vivo from a small number of stem cells (SC) could have enormous potential in a variety of clinical settings. Ex vivo generated HPC could support multiple cycles of chemotherapy, provide a transplant option for patients without matched donors, facilitate transduction of vectors into immature cells for gene therapy, and provide a tumor free product for transplantation. Last, ex vivo expansion of umbilical cord blood cells could abrogate the extended neutropenia and thrombocytopenia after transplantation with this product. Two phase I clinical trials and correlative laboratory studies are proposed to address whether ex vivo generated cells can provide short and long-term h e m a topoietic reconstitution in patients that received myeloablative chemotherapy. The first trial will determine whether the administration of cultured cells results in any additional infusion related toxicity and combines cultured cells with infusion of 2.5x106 CD34 positive cells/Kg non-manipulated G-CSF mobilized product (G-PBMC). If the toxicity is negligible, we will perform a second trial, whereby only cultured cells are infused after myeloablative chemotherapy. This second trial will allow us to conclusively determine whether our cultured cells can provide rapid early hematopoietic recovery and will also provide information on the long-term reconstitution mediated by this expansion product. For non-manipulated G-PBMC, the number of CD34 positive cells and/or CFU-GM correlate to the rate of neutrophil and platelet recovery after transplanta-tion. It is not known whether the infusion of large numbers of these cell populations correlate to the engraftment rate of cultured cells. This understanding is essential for optimizing production of cells ex vivo and will be invaluable for predicting patient recovery. Hence, in parallel with the clinical trials extensive phenotypic and functional analysis of the expansion product is proposed. The phenotypic and functional composition of the infusion product will be compared to the rate of engraftment to identify markers that correlate to hematopoietic recovery. In summary, the two clinical trials and correlative studies will provide important preliminary data to further evaluate the role of ex vivo generated hematopoietic products in the clinic.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA078166-01
Application #
2655951
Study Section
Subcommittee G - Education (NCI)
Program Officer
Wu, Roy S
Project Start
1998-04-01
Project End
2000-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
Goerner, M; Roecklein, B; Torok-Storb, B et al. (2000) Expansion and transduction of nonenriched human cord blood cells using HS-5 conditioned medium and FLT3-L. J Hematother Stem Cell Res 9:759-65