Non-Technical Abstract 
Infection with the human immunodeficiency virus (HIV) , the virus 
associated with the Acquired Immunodeficiency Syndrome (AIDS) , is 
often characterized by gradual impairment of the immune system 
leading to increased infections and an increased risk for the 
development of cancers, including lymphoma, a cancer of the lymph 
node cells. Drug therapy such as zidovudine (AZT) may temporarily 
slow the progress of HIV infection, but the disease usually 
progresses to a fatal immunodeficiency. Lymphomas in patients 
with HIV infection are usually treated with chemotherapy or 
radiation therapy which may provide a temporary remission, but 
recurrence of the cancer is common. This study is evaluating bone 
marrow transplantation as a therapy for both the lymphoma and HIV 
infection. Prior to bone marrow transplant very high doses of 
chemotherapy combined with total body irradiation (TBI) can be 
given in an attempt to destroy the lymphoma cells . This treatment 
will also destroy the normal bone marrow and the blood cells 
infected with HIV. Donor bone marrow will be given to replace the 
destroyed marrow. In an attempt to prevent HIV infection of the 
donated bone marrow and destroy any residual HIV infected cells, 
we will boost immunity to HIV with a treatment called adoptive 
immunotherapy . 
Most patients with HIV initially develop some immunity to the 
virus provided by lymphocytes which specifically recognize and 
kill HIV infected cells. The presence of these cells in the body 
appears to help prevent HIV spread and progression to AIDS. The 
chemotherapy and radiation therapy used to destroy the lymphoma 
cells will also destroy the lymphocytes providing this immunity to 
HIV. Therefore, we will attempt to isolate these specific 
lymphocytes that fight HIV from the patient's blood before the 
bone marrow transplant and grow these cells to large numbers in 
the laboratory. These lymphocytes will be given back to the 
patient after the transplant in an attempt to provide immunity to 
HIV and prevent the virus from infecting the new immune system 
developing from the donated marrow. We will insert a gene into 
the lymphocytes to be used in immunotherapy to provide a sensitive 
indicator of the survival of these cells after giving them back to 
the patient. Since this is a new experimental therapy, it is 
possible the transferred lymphocytes might cause side effects due 
to inflammation initiated when these cells contact residual HIV 
infected cells. Therefore, the gene inserted into the 
lymphocytes, termed HyTK, was selected to make a protein that will 
kill the cells if they are exposed to the drugs acyclovir or 
ganciclovir (used to treat herpes and cytomegalovirus infections) . 
The presence of this gene in the transferred lymphocytes should 
allow us to destroy them if they cause any serious side effects by 
administering ganciclovir. If the cells do not cause any side 
effects at all, but ganciclovir or acyclovir are required to treat 
a herpes virus infection developing after transplant, we will 
administer lymphocytes that were not modified by the gene transfer 
technique . 
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Recombinant DNA Research, Volume 15 
