MEDICINE RESEARCH : Bone-Marrow Transplant to Be Tested Against AIDS
Medical researchers in Los Angeles County intend to begin testing bone-marrow transplantation as a treatment for some AIDS patients, in light of a case in which a man appeared to have been purged of the AIDS virus after physicians replaced his bone marrow.
A team of transplant specialists at City of Hope National Medical Center in Duarte is among several groups nationwide that plan to test the experimental procedure on a small number of patients with AIDS-related lymphomas, or tumors of the lymph nodes.
The procedure, which entails eradicating an impaired immune system in hopes of cultivating a new one, is considered extraordinarily risky, however. Several dozen previous attempts at treating AIDS patients with similar transplants have produced disappointing results.
“I think we have to be very circumspect in how we proceed with the treatment using bone-marrow transplantation,” said Dr. Ronald Mitsuyasu of UCLA, who has tried the technique. “We don’t want to kill the patient in the process of trying to help them.”
The plan to test the procedure at centers in California, Washington, Minnesota and Maryland was fueled in part by a report from Johns Hopkins University in Baltimore, where researchers believe that they purged an AIDS patient of the human immunodeficiency virus.
The case, reported at the International AIDS Conference in Montreal last June and published Wednesday in Annals of Internal Medicine, involved a 41-year-old man whose defective bone marrow was replaced by researchers with marrow taken from a healthy sister.
The man, who was also treated with the anti-viral drug AZT, died of cancer 47 days after the operation. Researchers found no traces of the virus in his body either while he lived or in an autopsy performed after his death from his AIDS-related lymphoma.
“It’s an exciting case, but it’s just one,” said Dr. William Burns, a member of the team involved in the work. “It’s probably a year before we know if this is going to be something important for treating AIDS or not.”
Other experts in AIDS treatment raised similar reservations.
“It’s going to take patients living a lot longer to see if we really have been able to render that patient free of the (consequences) of the AIDS virus,” said Dr. Stephen J. Forman of City of Hope, whose team helped to analyze the Johns Hopkins case. “It may be that the AIDS virus may still be in the body and the AZT is preventing it from infecting the cells.”
“My concern is that there will be a misinterpretation that we’re dealing with a cure for AIDS, which this certainly is not,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
At least initially, the four medical centers intending to test the procedure plan to use it only on patients with AIDS-related lymphomas and leukemia. The reason is that patients with those conditions, even in the absence of AIDS, are sometimes treated with bone-marrow transplants.
The procedure used by the Hopkins group involves exposing the patient to high doses of chemotherapy and radiation. The purpose is to eliminate cancerous cells from the patient’s body and knock out the AIDS-impaired immune system to make way for transplanted marrow.
They then inject into the patient’s blood stream about a quart of bone-marrow cells drawn from the hip bone of a sibling donor. Those cells make their way into the patient’s bone marrow and begin to grow, generating new, healthy, immune-system cells.
At the same time, the patient is treated with intravenous AZT, a drug that has been proven to block replication of the AIDS virus. The AZT is intended to prevent any virus remaining in the body from infecting the new immune system cells.
Bone-marrow transplantation, which costs up to $200,000, is fraught with complications even when used in more traditional ways, such as against leukemia. As many as one-third of all patients die within the first year alone from the procedure itself, researchers said.
The complications include a condition called graft-versus-host disease, in which cells in the transplanted marrow attack the patient’s tissues. That condition can increase the patient’s susceptibility to infection--already a problem in AIDS patients.
The Johns Hopkins patient died from a relapse of his cancer, despite high doses of chemotherapy and radiation. Forman of City of Hope said that illustrates the fact that cancer cells are sometimes stronger than chemotherapy and radiation.
In other words, the therapy appeared to work against the AIDS virus, but failed to conquer the patient’s AIDS-related cancer.
Fauci said he had recently tested bone-marrow transplantation, without chemotherapy and radiation but with AZT, on 16 AIDS patients whose donors were identical twins. Marrow donated by identical twins is less likely to be rejected by the patient.
“We have found that apparently there is no lasting impact on the clinical course of the patient,” Fauci said in a telephone interview. “Some do well, some died, some have transient improvements. . . . Our experience is that the effects are only transient.”
Mitsuyasu, an assistant professor of medicine at UCLA’s AIDS Research Center, said UCLA had been conducting a study of bone-marrow transplantation in AIDS patients since 1983. But he said the university had tried the procedure on only three patients so far.
“We’ve always had enthusiasm for our study,” Mitsuyasu said. “It’s just that we want to select our patients carefully. . . . It’s a very aggressive treatment with a fairly high morbidity and mortality rate compared to other treatments.”
He said the procedure has other worrisome implications.
“The cost problem becomes a factor,” he said. “We’re talking on the order of $100,000 to $200,000 for a typical bone-marrow transplant. And that obviously is going to put a strain on the patient as well as the health care system.”
