conceivably could be held in check by the patient's own 
anti-tumor defenses, or by biomodulators such as interferon. 
The data to date strongly support further application of 
this approach in myeloma patients. 
Our protocol is a phase II trial in 24 chemotherapy- 
responsive patients with multiple myeloma. Transplantation 
of patients with chemotherapy-responsive disease at a point 
in time when their tumor mass is as low as possible should 
increase the chance of successful eradication of tumor. 
Aggressive treatment such as we suggest in this protocol 
should be used in patients most likely to benefit from it 
with long-term remission or cure, and other studies in 
patients with myeloma and lymphoma have suggested that 
patients with advanced chemotherapy-refractory disease are 
unlikely to benefit from high-dose therapy with autologous 
stem cell rescue. 18,19 
We propose to harvest both mobilized peripheral blood "stem 
cells" and 5-f luorouracil-primed bone marrow to use for 
autologous transplantation. Chemotherapy and growth-factor 
mobilized peripheral blood "stem" cells have been shown to 
"rescue" patients successfully after high-dose chemo- 
radiotherapy , and when given in combination with standard 
autologous marrow, speed recovery and thus decrease the 
morbidity and mortality of the transplantation procedure.- 20,21 
(G. Morstyn, personal communication) As discussed in more 
detail in section 3.0, this approach has already been found 
feasible in a small number of myeloma patients. We plan to 
obtain cyclophosphamide and G-CSF-mobilized peripheral blood 
stem cells via apheresis. In animal transplantation models, 
5-f luorouracil (5-FU) has been shown to stimulate cycling of 
early bone marrow hematopoietic progenitors, and use of 
marrow obtained from donor animals given 5FU pre-harvest has 
hastened hematopoietic reconstitution in ablated recipient 
animals. 22 A preliminary human Phase I-II trial done by our 
collaborators at the University of Virginia suggests that 
patients receiving 5-FU prior to marrow harvest recovered 
platelets more rapidly after autologous transplantation than 
historical controls . .(F^ Marc Stewart, personal 
communication) 
Patients will receive high-dose melphalan (140mg/m2) and 
1200 cGy total body irradiation, marrow-ablative agents 
found to be very active against myeloma tumor cells. Marrow 
and peripheral blood stem cells will be reinfused, and G-CSF 
will be given in an attempt to shorten the period of 
profound neutropenia. The transplantation of a combination 
~ of~ both - bonfe* marrow* artd~p6ripheral' blood cells as well as 
priming of the bone marrow with 5-f luorouracil should 
provide very rapid hematopoietic reconstitution, thus 
decreasing transplant-related toxicity. Alpha-interferon 
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