AuBMT for patients with ALL show a high relapse 
rate, greater than 80% for patients transplanted in 
second or later remission, but preliminary studies 
suggest that the overall survival may be equivalent 
to results with patients receiving AlloBMT (10,27- 
29) . 
AuBMT has an advantage over conventional 
chemotherapy in allowing intensification of 
therapy, permitting 1.5 to 3 times the drug dosage 
administered in conventional chemotherapy protocols 
(13) . The advantages of AuBMT over AlloBMT include 
applicability to older patients, no restrictions 
related to donor availability, no graft rejection, 
and no severe graft-versus-host disease. 
The disadvantages of AuBMT include the potential 
loss of the "graft versus leukemia" effect and 
inadvertent transplantation of marrow contaminated 
with residual leukemia. Human syngeneic transplants 
have a higher relapse rate (59%) when compared to 
allogenic transplant (18%) for first remission AML 
supporting the contention that the graft may have 
an important antileukemic effect (30) . The loss of 
any anti-leukemic effect of an allograft is 
currently offset by the decreased treatment related 
mortality of syngeneic BMT. The incidence and 
importance of inadvertent transfer of leukemic 
cells in the transplanted marrow is not known and 
is the question being addressed in this protocol. 
1.2) Rationale for the use of retroviral-mediated gene 
transfer in bone marrow transplant 
A major issue related to AuBMT is determining 
whether there is transfer of leukemic cells in the 
transplanted marrow. The significance of residual 
leukemia is difficult to assess since the factors 
leading to leukemic relapse after AuBMT are not 
known. Relapse may depend on recurrent leukemia in 
the transplanted marrow, insufficient conditioning 
(i.e. leukemic cells survive the BMT ablative 
regimen) , or both. 
If elimination of residual leukemia is critical to 
the success of AuBMT, then methods to "purge" the 
marrow of leukemic cells should decrease the 
relapse rate. A variety of purging methods have 
been evaluated using monoclonal antibodies (30-33) 
and drugs such as 4-HC, Asta Z 7557 and VP-16 
(32,34-36). While some reports are encouraging the 
patient numbers are small and the follow-up is 
Recombinant DNA Research, Volume 15 
[469] 
