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