of G-CSF following standard chemotherapy for breast cancer 
led to increased numbers of peripheral blood progenitor^ 
cells generated during the hematologic recovery phase. 
A number of other approaches in different animal 
systems leads to enhanced marrow recovery after either 
radiation cr chemotherapy. These manipulations have included 
exposure to_ low dose irradiation, chemotherapy, or 
endotoxins . ^”- 4 Bradley and ccwcrkers have shown an 
increased ability of marrow from animals "primed" with 
5-f luorouracil to recover when narrow was transplanted into 
otherwise lethally irradiated animals. 34 
In 19 vS Bradley and Hodgson described the high 
proliferative potential colony forming cell (EPP-CFC) , 
characterized by the formation of large colonies of 
macrophages (diameter > .5 mm) in nutrient agar cultures of 
normal mouse bone marrow and bone marrow from mice 
pretreated with 5-f luorouracil (5-FU) . ~ 4 Marrow exposed in 
vivo to 5-FU has the capacity to rapidly repopulate lethally 
irradiated animals over a period of 4 to 10 days. The 
HFP-CFC seems to correlate with marrow renewal potential. 
Colonies formed from these ceils contain an average of 5 x 
10 4 * cells which is 10 to 100 times the size of other 
colonies such as CFU-C. Multifactor combinations such as 
GM-CSF and IL-3 in agar cultures lead to the formation of 
EPP-CFC. 35 
In marrow obtained from patients following treatment 
with 5 -FT in vivo, McNiece and co-workers have described 
what appears to be the human equivalent of the murine 
EPP-CFC. 2 These cells occur at very low frequency in normal 
marrow or pre-FU marrow (approximately 1-1.5 per 100,000 
ceils plated) and appear to be generated by a 
synergistically interacting combination of growth factors. 
5-FU modulation of human marrow has been evaluated 
recently as an alternative source of hemopoietic 
reconstitution following autologous marrow transplantation. 
(F.M. 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 KPP-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 KPP-CFC's tended to occur in patients 
treated with 5-FU 14-13 days and 10 days prior to marrow 
harvest respectively. 
Post-FU marrow was infused into 15 patients following 
high dose cyclophosphamide, BCNU, and etoposiae (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 
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Recombinant DNA Research, Volume 16 
