Human Gene Therapy Subcommittee - 11/21-22/91 
aspect to consider. 
Dr. Parkman provided information regarding the present status of bone marrow 
transplantation for the treatment of patients infected with HIV. HIV positive patients 
receiving short-term AZT exhibit no interference with hematopoietic engraftment 
following bone marrow transplantation. Patients who receive long-term AZT 
demonstrate granulocyte suppression; however, at the dose levels proposed in Dr. 
Greenberg's protocol, there have been no negative effects on engraftment. 
Regarding the efficacy of the proposed treatment, Dr. Parkman explained that non- 
Hodgkin's lymphoma is universally fatal in patients who have acquired immunodeficiency 
syndrome (AIDS). There is no effective therapy for the disease, and patients die very 
rapidly. One of 6 patients receiving allogeneic bone marrow transplant from an identical 
twin has exhibited increased survival out to 16 months. The remaining 5 patients died as 
a result of recurrence of their lymphoma or because of opportunistic infections like 
cytomegalovirus (CMV). Since the therapy of choice for CMV is ganciclovir, the 
investigators should address how this impacts on clinical decision making. In the one 
patient who died of recurrent lymphoma following bone marrow transplantation, there 
was no detectable HIV. Therefore, the bone marrow transplant not only purges the 
patient of neoplastic lymphoma cells but of HIV infected cells as well. It is relatively 
easy to eliminate circulating cells that are infected with HIV; however, the slowly 
dividing cells such as macrophages are a concern. How is HIV eliminated in non- 
hematopoietically derived cells such as neurons? Since the investigators propose to 
administer T cells that are specific for HIV, it may be possible to eliminate the 
remaining HIV infected cells. 
Dr. Parkman explained that HIV patients often develop resistance to AZT; the 
investigators have avoided this complication by the addition of exclusion criteria that 
patients will not have received AZT for greater than three months or that the virus still 
demonstrates AZT sensitivity. The patients will receive chemotherapy or radiation to 
kill the lymphoma cells in addition to the hematopoietically derived cells, followed by 
allogeneic bone marrow transplantation from a histocompatible sibling and the use of 
AZT. AZT is administered to prevent the infection of the transplanted cells with HIV. 
The T cell clones that will be administered should recognize the HIV viral antigens and 
kill the remaining infected cells. 
Dr. Mclvor noted that 1 AIDS patient who received a bone marrow transplant and AZT 
had no detectable levels of HIV out to 16 months. What levels of HIV were observed in 
the 5 patients who died following this procedure? Dr. Parkman responded that 4 of the 
patients had detectable levels of HIV, and 3 of the 4 had AZT-resistant HIV. Dr. 
Epstein asked if the infusion of the cloned T cells is dependent on being able to mark 
these cells with the HyTK gene. 
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