transplant treatment with interferon induced cytogenetic 
remissions. 2 Therefore, autotransplantation may convert 
some previously resistant patients to interferon responsive. 
Mechanism of Relapse Following Autologous Marrow 
Transplantation for CML : 
Chronic myelocytic leukemia is malignancy of 
pluripotential stem cells, characterized by specific 
cytogenetic and molecular abnormalities. 15 The Philadelphia 
chromosome (t[9;22] [q34;qll]) is found in over 95% of 
patients presenting with the characteristic clinical 
disease. The Philadelphia translocation results in a 
transposition of the abl gene from its position on 
chromosome 9 to a 5.8 kb breakpoint region on chromosome 22, 
termed the breakpoint cluster region or bcr. The bcr-abl 
gene is translated into a p210 protein with tyrosine kinase 
activity. Although the bcr-abl gene may be found in other 
types of leukemia (e.g. 25-35% of adults with acute 
lymphoblastic leukemia) , for an individual patient with CML 
the bcr-abl gene provides a highly specific molecular marker 
for leukemia cells. 15 Techniques such as the polymerase 
chain reaction (PCR) to distinguish the RNA product of bcr- 
abl DNA may be used to detect very small numbers of leukemia 
cells analyzed in vitro, either from individual colony- 
forminq cells or from pooled populations of marrow or blood 
cells . ^ 5 
Techniques to purge bone marrow of neoplastic cells 
have theoretical appeal, but their usefulness in patients 
remains unproven. Large, prospective controlled studies 
would be required to definitively determine the benefit of 
purging based on clinical outcome alone. 23 Proof of 
efficacy is desirable since these methods often damage 
normal marrow cells and impair hemopoietic recovery. 6 To 
assess whether purging is likely to be useful in CML, it is 
important to determine whether relapse occurs due to a 
failure of the transplant conditioning regimen to eradicate 
systemic disease (endogenous relapse) or, due to a 
reinfusion of contaminating leukemia cells (graft-related 
relapse) . In humans with CML or other neoplastic diseases no 
studies have adequately addressed this question since it is 
impossible to distinguish the autografted leukemia cells 
from the leukemia cells which survive intensive therapy. 
The use of gene transfer techniques to mark cells from 
the marrow or peripheral blood stem cell graft may permit a 
more complete understanding about the origin of relapse 
after autologous transplant. If relapse is primarily related 
to survival of endogenous cells, treatment with more 
intensive conditioning regimens may be warranted to decrease 
systemic recurrence. If relapse originates from either the 
autografted marrow or the peripheral blood progenitor cells, 
strategies should be targeted toward in vitro purging of 
Recombinant DNA Research, Volume 16 
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