increase the efficiency of transduction. Two different 
marking vectors will be used to mark the bone marrow and 
peripheral blood target cells respectively. These two 
vectors will be distinguishable by PCR analysis , and will 
allow identification of cells originating from the marrow 
versus the peripheral blood graft post-transplant. The 
transduced marrow and peripheral blood populations will 
given back to the patient along with non-transduced marrow 
and peripheral blood. The kinetics and biology of 
autologous reconstitution can be studied if successful 
marking of progenitors or stem cells is obtained, and if 
patients relapse post-transplant, the presence of marked 
tumor cells will indicate origin of the relapse from the 
autografted marrow or peripheral blood. This type of 
information could help guide future approaches to 
autotransplantation, especially as regards the need for 
purging autografts of residual tumor cells. 
3 . 0 BACKGROUND 
3.1 MULTIPLE MYELOMA: THERAPY : 
Despite the rapid progress made in the treatment of other 
hematologic malignancies over the past three decades, the- 
uniformly dismal prognosis of multiple myeloma has not 
changed since the introduction of melphalan and prednisone 
over twenty-five years ago. 19,25 The median survival ranges 
from 30-35 months. Survival curves for responders to 
chemotherapy never parallel those of age-matched controls, 
indicating that patients are not cured of their disease with 
currently available standard therapy. 
STANDARD CHEMOTHERAPY: Investigators have attempted to 
intensify the initial treatment of multiple myeloma using 
multi-drug, non-cross-resistant regimens analogous to those 
that have been so successful in producing complete remission 
or cure in patients with other lymphoid malignancies. 
Various combinations of vincristine, adriamycin, melphalan, 
cyclophosphamide, carmustine (BCNU) , prednisone and other 
agents have been studied, and none show any clear advantage 
..over. .standard melphalan and prednisone in response as 
measured by decrease in plasma or urine monoclonal 
paraprotein or in survival. 26,27 Reasons for this resistance 
to chemotherapy are unclear, but may result from the low 
fraction of plasma cells or more immature myeloma "stem 
cells" in cell cycle and thus sensitive to standard 
chemotherapy, or the propensity for myeloma cells to rapidly 
acquire or . intrinsically possess high levels of the 
multidrug, transporter (p-glycoprotein) . 7,28,29 
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