3.3.1 4-Hydroxy-peroxy-cyclophosphamide (4HC) 
This cytotoxic drug is the most widely used agent for purging marrow 
from patients with AML. Although the drug damages normal 
progenitor cells and slows engraftment, we have chosen it in part 
because it represents the closest to a "gold standard" for purging 
techniques and in part because the institution already has considerable 
experience with the drug in a Phase 1 study that was part of the 
AML87 protocol. The drug will be used at a fixed dose in the present 
investigation. 
3.3.2 Interleukin-2 (IL2) 
IL2 activated killer cells are able to destroy viable malignant blast cells 
ex vivo and in vivo in bone marrow. Recently, studies by the 
Leukemia/Bone Marrow Transplantation program of British Columbia 
and by the Terry Fox laboratories in Vancouver have shown that ex 
vivo culture of leukemic patient marrow for 7 days in the presence of 
IL2 will generate a high level of activated killer cells. IL2 treatment 
produces little impairment of the subsequent growth of primitive 
marrow progenitor cells. In a pilot study, 8 of 9 patients receiving 
marrow cultured ex vivo with IL2 subsequently engrafted. Their 
median time to 500 neutrophils was 53 days (range 20-71 days). This 
immunomodulatory approach to marrow purging appears particularly 
worthy of evaluation, given our previous and current experience with 
IL2 treatment of patients with AML. Appendix F contains a relevant 
pre-print. 
STUDY OUTLINE AND SAFETY 
This study proposes to transduce marker genes into two separate aliquots of marrow 
obtained for ABMT in patients in remission of AML. Each aliquot will be purged by 
a different technique and the marrow cryopreserved. The marrow will be reinfused 
after the patient has received ablative therapy. The vectors to be used in the 
transduction studies are the closely related but distinguishable retrovirus vectors 
LNL6 and GIN. Safety considerations for each of these vectors were discussed in 
detail in the original AMLREM protocols. 
Recombinant DNA Research, Volume 17 
