5-FU modulation of human marrow has been evaluated recently 
as an alternative source of hemopoietic reconstitution 
following autologous marrow transplantation. (F. Marc 
Stewart, personal communication) Twenty-one patients were 
treated with 5-FU ( 15mg/kg-45mg/kg) IV for 1-3 days 
administered 6-22 days prior to bone marrow harvest. 
Toxicity of the 5-FU was minimal. Cerebellar toxicity was 
observed in several patients receiving more than 15 mg/kg 
per day. Numbers of CFU-C's and HPP-CFC's were increased in 
marrow in patients pre-treated in vivo with 5-FU. Although 
no definite correlation between dose or timing of 5-FU 
administration could be made with respect to CFC generation, 
peak CFU-C's and HPP-CFC's tended to occur in patients 
treated with 5-FU 14-18 days and 10 days prior to marrow 
harvest respectively. 
Post-FU marrow was infused into 15 patients following high 
dose cyclophosphamide, BCNU, and etoposide (CBV) . 17 
(historical controls) were treated with CBV and autologous 
marrow transplantation but did not receive 5-FU prior to 
marrow harvest. The groups were comparable for diagnosis and 
prior therapy. In the 5-FU-treated group vs. control, median 
recovery times for platelet count to 50,000/mm3 were 20 days 
and 30 days respectively (p=0.01) and for platelet count to 
100,000/mm3 were 23 days and 30 days respectively (p=0.007). 
Neutrophil recovery was not significantly changed. Thus, - 
5-FU treatment of patients prior to marrow harvest results 
in enrichment of multifactor-responsive HPP-CFC and possibly 
provides superior platelet recovery. 
In addition, 5-FU has been used in murine systems and 
primate models to enhance retroviral transduction of 
progenitor cells. Patients in this protocol are treated 
with 5-FU prior to marrow harvest in order to 1) enhance 
marrow recovery post-transplant and 2) continue to evaluate 
the retroviral transduction efficiency of pre and post-FU 
marrow samples in vitro. The data presented above reassures 
us that 5-FU treatment of patients in vivo allows safe and 
possibly improved marrow recovery post-transplant. 
3.3 PERIPHERAL BLOOD STEM CELL TRANSPLANTATION 
It has been known for twenty years that the peripheral blood 
contains progenitor cells, and recent advances in cell 
separation technology have allowed harvest of these 
circulating progenitors from humans. The combination of 
peripheral blood progenitors and autologous bone marrow was 
noted to produce more rapid engraftment than bone marrow 
given alone. 20,21 Peripheral blood progenitors or "stem 
cells" without additional marrow support were found to be a 
reliable source of hematopoietic support after high-dose 
therapy. 64 ; Collection of peripheral blood cells during 
Recombinant DNA Research, Volume 16 
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