NEW ORLEANSThe use of highly active antiretroviral therapy (HAART) in HIV-infected individuals with lymphoma may make it possible for them to receive high-dose chemotherapy with autologous stem cell transplantation (ASCT), according to a study conducted at City of Hope National Medical Center, Los Angeles.
Previously, it had been thought that ASCT, which is the best available treatment for relapsed lymphoma, would not be appropriate for patients with HIV because their weakened immune systems could not tolerate high-dose chemotherapy, Amrita Y. Krishnan, MD, said at the American Society of Hematology (ASH) annual meeting. But this study demonstrates that the treatment is safe and effective for certain HIV-positive lymphoma patients.
The study included six HIV-positive patients with non-Hodgkins lymphoma and one with Hodgkins disease. All patients were receiving concomitant combination anti-HIV therapy with undetectable HIV viral loads before stem cell collection, and were on prophylaxis for pneumocystis and mycobacterium infections both before and after transplant.
One of the non-Hodgkins disease patients failed to produce enough stem cells for transplantation. The six remaining patients underwent stem cell harvest followed by transplant. So far, Dr. Krishnan said, five remain in remission, one for as long as 21 months.
The fact that there was no liver toxicity and that these patients didnt die of infections following transplant is encouraging, Dr. Krishnan said. It allows us to approach these patients in a similar way to people who are HIV negative. She noted, however, that these patients were carefully selected and did not have any opportunistic infections at the time of treatment. Unfortunately, people with uncontrolled HIV infection would not likely survive this procedure, she said.
The study was supported by City of Hope and by the Lymphoma Research Foundation of America.
Gene Therapy Study
Four of the seven patients in the transplant study had a portion of their stem cells set aside for a gene therapy study. An anti-HIV gene containing two types of anti-HIV ribozymes was engineered to target and sever two critical HIV genes, thus rendering the virus ineffective. It was inserted into the stem cells, which were then returned to the patients after high-dose chemotherapy, along with stem cells not containing the gene.
Although these are early results, we are very encouraged that stem cells containing anti-HIV genes have engrafted into the bone marrow of all of the persons enrolled in our current trial, John Zaia, MD, director of virology and infectious diseases, City of Hope Cancer Center, said at the ASH meeting.
The researchers had discovered in an earlier safety study that stem cells containing the gene would not engraft in patients who had not undergone myelo-ablative chemotherapy. The bone marrow of these HIV-positive patients was intact, so there was no space for the reinfused stem cells containing the anti-HIV genes, Dr. Zaia explained.
However, in the four patients in the current study, the anti-HIV gene engrafted into the bone marrow, appearing in the blood at a frequency of about 1 in 10,000 cells, approximately 100 times more than was observed in the initial study.
This is an early observation, and we are continuing to follow these patients closely to determine how long the anti-HIV gene will continue to circulate, Dr. Zaia said.
The study was conducted in collaboration with investigators from Childrens Hospital, Los Angeles; Chiron Corporation; and Ribozyme Pharmaceuticals, Inc.