Appendix C 
SCIENTIFIC ABSTRACT 
Replication incompetent, recombination incompetent retroviral 
vectors (GINa and LNL6) will be used to mark autologous peripheral 
blood and marrow cells removed and stored at the time of 
cytogenetic remission or re-induction of chronic phase in 
Philadelphia chromosome positive CML patients who have developed 
blast crisis or accelerated phase and have been reinduced into 
chronic phase following Daunomycin, high-dose Ara-C, and GM-CSF 
therapy. This study will also compare the relative efficiency of 
the peripheral blood and marrow to generate hematopoietic recovery 
after transplantation. We estimate that between 0.6 and 2 x 10 6 
CD34 positive cells/kg will be infused and that between 600 and 
2000 leukemia cells will be marked with NEO in the autologous cells 
used for transplant. It is not known how many CML blastic leukemia 
cells are present in the systemic circulation following induction 
of the chronic phase or a cytogenetic remission by Daunomycin, 
high-dose Ara-C, and GM-CSF, but a significant number of patients 
are in cytogenetic remission (7) . We will look for the number of 
NEO-marked cells using a methylcellulose late progenitor colony 
culture system and a PCR assay for the NEO gene used previously 
(5) . In the CML cells under analysis, the percent of these NEO- 
marked cells which are leukemic can be determined by a PCR assay 
for the bcr-abl mRNA positive CML cells (5) . These studies will 
clarify if relapse arises from the leukemic CML blast cells present 
in the autologous cells infused after TBI , VP-16, and cytoxan (if 
polyclonal CML NEO-marked blastic cells appear at the time of 
relapse) , or if residual systemic disease contributes to relapse 
(if none of the CML leukemic blasts at the time of relapse contain 
the NEO gene) . These studies will help us evaluate purging and 
selection of peripheral blood or marrow as a source of stem cells 
for transplant. 
Recombinant DNA Research, Volume 15 
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