active than cyclophosphamide or other marrow ablative 
regimens. 45 
Most recently, one group has reported using interferon 
maintenance after autologous transplantation. Preliminary 
data has suggested that initial VMCP or VAD, followed by 
high-dose melphalan and TBI with autologous bone marrow 
rescue, and then maintenance interferon is a feasible 
approach. 24 53% of the initial 19 patients went into CR, 
with follow-up still too short to assess impact on survival 
or stability of remissions. 
3.2 5-FU MODULATION OF HUMAN BONE MARROW: 
Theoretically, shortening the time after transplantation 
required for marrow recovery would improve survival and 
lessen morbidity. Techniques to shorten recovery in humans 
have included the use of recombinant human hemopoietic 
growth factors following transplantation of stem cells 46 ' 51 
or the use of chemotherapy-mobilized peripheral blood stem 
cells with or without growth factors, 21 ' 52 ' 56 A number of 
other approaches in different animal systems leads to 
enhanced marrow recovery after either radiation or 
chemotherapy. These manipulations have included exposure to 
low dose irradiation, chemotherapy, or endotoxins prior to 
marrow harvest 22,57 ' 61 . Bradley and coworkers have shown an- 
increased ability of marrow from animals "primed" with 
5-f luorouracil to recover when marrow was transplanted into 
otherwise lethally irradiated animals. 22 
In 1979 Bradley and Hodgson described the high proliferative 
potential colony forming cell (HPP-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 pre-treated with 5-f luorouracil 
(5-FU) . 22 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 HPP-CFC seems to correlate with 
marrow renewal potential. Colonies formed from these cells 
contain an average of 5x 104 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 HPP-CFC. 62 
In marrow obtained from patients following treatment with 
5-FU in vivo, McNiece and co-workers have described what 
appears to be the human equivalent of the murine HPP-CFC 63 . 
These cells occur at very low frequency in normal marrow or 
pre-FU marrow (approximately 1-1.5 per 100,000 cells plated) 
and appear to be generated by a synergistically interacting 
. combination of growth factors. 
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Recombinant DNA Research, Volume 16 
