existing in vitro culture assays, integrate these 
viruses. Ten to thirty percent of leukemia cells 
integrate these viruses. The in vitro growth of the 
normal and leukemia cells is not reduced by exposure to 
the viruses. Our in vitro data has suggested that the 
two viruses, LNL-6 and GINA, which differ only in small 
stretches of neutral sequences introduced for marking 
which are detectable by PCR, transduce 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 sufficient numbers of 
progenitor cells and leukemia cells such that these 
marked cells can be detected after transplant. 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. At the 
time of relapse, Dr. Brenner has shown that some of the 
leukemia cells also contain the retroviral marker. 
The present protocol is also designed to resolve the 
following question in CLL patients infused with purged 
autologous marrow: does the origin of relapse involve 
the infused autologous cells or systemic disease? In 
this study, autologous cells are collected after 
induction of a remission. The marrow cells are purged 
with CD3 4 positive selection, and the virus marked with a 
vector LNL-6. The cells are then fractionated with 
monoclonal antibodies to the CD19 lymphoid antigen. A 
second virus, GINa , is used to mark these cells. The 
autologous cells are then reinfused after intensive 
preparative therapy. This program may resolve the origin 
of relapse of CLL cells in patients in whom collection of 
autologous cells, delivery of intensive therapy, and 
autologous transplant is conducted at a time of 
hematological remission induced by conventional dose 
therapy. This protocol will also independently analyze 
the efficacy of the CD34 and CD19 purging procedures. 
CLL is a disease in which this question can be answered 
since the polymerase chain reaction assay (PCR) , 
fluorescence in situ hybridization (FISH) , and classical 
. metaphase cytogenetic assays are available for detection 
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Recombinant DNA Research, Volume 16 
