1.0 OBJECTIVES 
1.1 To use transduction of both the GIN and LNL6 marker retroviruses into 
separate portions of each patient's autologous marrow to determine: 
a) whether purging eliminates gene marked malignant cells from the 
harvested marrow, so that marker genes are absent in the malignant 
population at the time of relapse. 
b) whether marrow purging with 4HC or with IL2 is more effective at 
preventing relapse with gene marked malignant cells. 
c) how each method of purging modifies the pattern of autologous 
reconstitution. 
1.2 To estimate the continuous complete remission rate at 2 years for children 
with AML in first complete remission treated with 4HC and IL2 purged 
Autologous Bone Marrow Transplant (ABMT). 
2.0 BACKGROUND 
2.1 Current Status of Therapy for Acute Nonlymphocytic Leukemia 
Despite improvements in chemotherapy regimens and supportive care, 15% 
to 20% of children with acute myeloid leukemia (AML) fail to achieve 
complete remission (CR) (1-4). Further, most children who achieve CR then 
relapse and in most studies the median duration of complete continuous 
remission (CCR) rarely exceeds 18 months. Long-term survival is realized in 
20-40% of patients treated with current cytotoxic drug therapy. Reinduction 
chemotherapy regimens have limited success; brief second CRs are achieved 
in only 40% to 50% of patients (1-4). 
The major therapeutic problem in AML is effectively eliminating the residual 
leukemic cells after patients achieve a complete remission. Explanations 
proposed for treatment failure include: (1) variations in patients' systemic 
drug metabolism leading to insufficient exposure of leukemic cells to the 
active drug; (2) variations in leukemic cellular metabolism of drugs leading 
to insufficient leukemic cell kill; (3) the development of multidrug resistance, 
either classical (mediated by the MDR1 gene product) or "atypical" in nature; 
(4) inability of maintenance therapy to eliminate the residual leukemic cell 
burden due to failure of the clonogenic leukemia cells to enter the cell cycle, 
thus precluding cytotoxic effects of S-phase-specific drugs (1-4). 
Recombinant DNA Research, Volume 17 
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