normal and leukemic cells at equivalent frequencies. Other 
laboratories (Malcolm Brenner's, St. Jude) have confirmed 
these findings. 
The work of Brenner already has suggested that the 
retroviruses integrate into early progenitor cells and that in 
unpurged AML patients, sufficient number of blasts are marked 
so as to contribute to relapse. The NIH Recombinant DNA 
Advisory Committee and the FDA also support this view. 
The Recombinant DNA Advisory Committee of the NIH has approved 
a protocol by Dr. Malcolm Brenner of St. Jude Children's 
Hospital which is designed to test in acute myelogenous 
leukemia if relapse occurring following intensive therapy and 
infusion of unpurged autologous reconstitution results from 
residual systemic disease or disease that is infused with the 
autologous transplant. These studies have already shown that 
the normal cells are marked with the GINA virus after 
transplant and that at the time of relapse, that some of the 
leukemia cells also contain the retroviral marker. 
The present protocol is designed to resolve a related question 
in second chronic phase CML patients: does the origin of 
relapse involve the infused autologous cells or systemic 
disease, and do the purged peripheral blood or marrow 
autologous cells differ in their capability to generate normal 
hematopoietic recovery or relapse after transplant? In this 
study, autologous cells are collected after reinduction of the 
second chronic phase. When no accelerated phase or blast 
crisis phase blasts are morphologically detectable, the marrow 
and peripheral blood are purged, with CD34 positive selection, 
and the virus marked with a vector LNL-6 (peripheral blood) 
and GINa (marrow) and stored. The autologous cells are 
reinfused after intensive therapy. This program may resolve 
the origin of relapse of Ph+ blast cells in patients in whom 
collection of autologous cells, delivery of intensive therapy, 
and autologous transplant is conducted at a time of 
cytogenetic or hematological remission induced by conventional 
dose therapy, and the relative contribution of marrow or 
peripheral blood to the recovery of normal hematopoietic cells 
after transplant. 
CML is a disease in which this question can be answered more 
decisively than in AML since the polymerase chain reaction 
assay (PCR) , fluorescence in situ hybridization (FISH) , and 
classical metaphase cytogenetic assays are available for 
detection of the leukemic cells in CML. The M. D. Anderson 
program will consist of taking 30% of a population of purged 
autologous cells, which are to be used to reconstitute 
hematopoiesis following TBI, VP-16, and cytoxan, exposing it 
in vitro to the replication-incompetent GINa and LNL-6 neo 
positive retroviral vectors, thus marking the cells in vitro, 
and then returning those marked cells along with the rest of 
the autologous stem cells to restore hematopoiesis after 
Recombinant DNA Research, Volume 15 
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