1.0 OBJECTIVES 
1.1 To estimate the continuous complete remission rate at 2 years for children 
with AML in first complete remission treated with Autologous Bone Marrow 
Transplant. 
1.2 To use transduction of marker genes into autologous marrow to determine: 
a) whether the source of relapse after ABMT for AML is residual 
malignant cells in the harvested marrow or in the patient, and whether 
marrow purging is therefore rational. 
b) whether the majority of AML, which lack genetic markers, represent 
abnormalities in a multilineage progenitor cell, and whether therefore, 
autografting^tensified chemotherapy is ever likely to augment the cure 
rate. 
c) the mechanisms of autologous reconstitution, and the effects of stimuli 
which modify the process. 
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). 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 
less than 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. Bone marrow transplant offers 
better disease control, but the criteria for patient selection and the best timing 
for trsmsplantation remain controversial, and most patients lack a suitable 
donor. 
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 MDRl gene product) or "atypical" in nature; 
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Recombinant DNA Research, Volume 14 
