The Body Covers: The 4th International AIDS Malignancy Conference
May 16-28, 2000
Abstract 60: Mobilization of Peripheral Blood Progenitor Cells and Engraftment Following High-Dose Chemotherapy for AIDS-Lymphoma.
Authors: Krishnan, Molina, Zaia et al.
Abstract S19: Treatment of AIDS Lymphoma with High-Dose Chemotherapy and Genetically Modified Stem Cells: A Model for Evaluation of Gene Therapy.
Authors: Zaia, Krishnan, Rossi, et al.
In a stem cell transplant, patients have white blood cells (the infection-fighting cells) removed from their blood stream by a machine and put into a plastic bag like those used for blood transfusions. These cells are then sorted to remove the ones that can't reproduce. The remaining cells, the "stem cells," are saved and frozen to use later to repopulate the immune system of the patient after chemotherapy. The patient then receives very high doses of chemotherapy, much higher than they could tolerate without transplantation. All of their white blood cells are killed off by the chemotherapy. Without white blood cells, they would die of an inability to fight infection. However, the stem cells are infused after the chemotherapy treatment has been completed, and this allows patients to regenerate their white blood cells without difficulty. Higher doses of chemotherapy potentially leads to a higher chance of cure, even in people who have relapsed with their cancer. Although this is commonly performed in HIV-negative patients with various forms of cancer, the experience in AIDS is quite limited, and probably represents less than 20 or 30 transplants.
This study had an interesting twist. Before re-infusion of the white blood cells they were treated with a virus that was modified in the laboratory. A length of DNA was inserted into the virus, and the virus and stem cells were mixed. The virus attached to the cells and injected the DNA into the cells, which then spliced into the cell's DNA, and the viral DNA then becomes just another bit of the cell's DNA. However, that DNA causes the cell to produce an enzyme that breaks down HIV so that it can't infect the cell. Potentially then, these patients could become HIV-resistant and have a smaller drop in their T-cell count. This process is called "gene therapy."
The investigators observed that this gene was present in a number of the patients after the transplantation was complete. Although it is too soon to tell what effect this gene therapy has on the individual's resistance to HIV, 7 out of 9 patients have not relapsed with their lymphoma, and are doing quite well. This is a very unusual outcome in this population from a cancer standpoint, and suggests that the stem-cell transplantation may be effective therapy for selected patients with relapsed or resistance lymphoma that are in good enough condition to tolerate the high doses of chemotherapy required.
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