The Bay Area Reporter - July 4, 1995
Matthew Sharp, ACT UP/Golden Gate Writer's Pool

People with AIDS-lymphoma are living longer for the same reasons that people with AIDS are living longer: improved prophlaxis against opportunistic infections. But as people survive longer they also run the risk of developing lymphoma.

As people with AIDS are living longer, there is more of a chance of coming down with the disease regardless of CD4 status (Munoz A., Am J of Epid.137(4):423-438, 1993). Interestingly, central nervous system lymphoma is more related to CD4 counts; 75 percent of those with the CNS lymphoma have a CD4 count of under 50.

Symptoms of lymphoma can range from rapidly enlarging asymmetrical nodes to chronic GI (gastrointestinal) problems, from jaundice to constitutional symptoms. It's important to realize that many lymphoma symptoms are similar to other HIV and opportunistic infection symptomatology. Extra nodal disease (outside the lymph nodes) is seen in 80% of AIDS-lymphomas.

Blood tests to detect lymphomas are not available. Levels of LDH, a liver enzyme, may give some indication, but other conditions also elevate LDH. A definitive diagnosis of lymphoma almost always has to be proven with a biopsy. A less invasive method, fine needle aspiration (FNP), is less effective than a regular biopsy because it produces less tissue.

'Bogus data'

Just how often AIDS lymphoma occurs has been difficult to estimate - and a matter of some controversy. A 1991 NCI (National Cancer Institute) study found alarmingly high lymphoma in AIDS, but Lawrence Kaplan, M.D., an Oncology/HIV specialist from San Francisco General Hospital, says that "the data is bogus and highly biased." Estimates from the Center for Disease Control, like so many of the CDC's numbers, are probably low due to under- reporting. Kaplan says that SFGH sees approximately 30 people with AIDS a year with lymphoma, and that the number has stayed relatively constant over the years.

In lymphoma research, data has been hard to come by and people with these diseases are difficult to enroll in clinical trials. Managed healthcare plans may not enable their "clients" to go to county hospitals such as SFGH, where some of the most important oncology research is taking place. Also, private physicians are reluctant to release their patients to other institutions for fear of losing them.

Chemotherapy is still the standard in treating lymphoma though the immunosuppressive effects can outweigh the benefits. In an ACTG (AIDS Clinical Trials Group) study of a standard chemotherapy regimen (BACOD) with GM-CSF (used to build white blood cell reserves) 50 percent of patients achieved a complete response. More research with the combination, by Kaplan et al., shows that a delayed administration of GM-CSF may reduce neutropenia (white blood cell depletion). Furthermore, a recent important ACTG study (142) shows that the same response rates can be attained by using half-dose chemotherapy. This is important because chemotherapy is so toxic in AIDS that many people have to forego treatment; for some a lower dose would allow therapy to continue. Kaplan stated that more approaches need to be studied in lymphoma. "We can't go much further with chemotherapy. We need to look at non-myelotoxic [bone marrow suppressive] therapies."

A new chemical treatment that is non-myelotoxic called MGBG (mitoguazone) has been looked at in combination with CHOP, another chemotherapeutic regimen. Kaplan says, "It may be useful in improving quality of life, but is not the answer with balky disease." The excitement with this therapy may be drug company (Sanofi-Winthrop) induced. More studies are underway.

Lymphoma research gaining ground

Another class of drugs that Kaplan feels are promising are camptothecins. Topotecan, produced by SmithKline-Beecham, may be useful because it has shown to be an anti-HIV drug. (Crumpacker WS-A17-5 Int. Conf. on AIDS, 1993) It is also being researched for PML (progressive multifocal leukoencehalopathy). Kaplan recently designed a protocol for this drug that will be studied at SFGH.

The field of AIDS-lymphoma research is gaining ground. Kaplan feels as though progress has been made with standard chemo, and the next step needs to be taken to further options and increase survival. Research into the molecular make-up of lymphoid tumors is needed to develop better theories for treatments. Ultimately, the goal would be to combine biological methods with chemotherapy for the best results.

There are two real areas of interest in biological methods in lymphoma research: 1) antibody-directed, and 2) cytokine-directed.

Antibody-directed therapies use special lymphoid antibodies to deliver a toxin called ricin to the surface of lymphoma cells, where the toxin would hopefully kill them. One such study, using the CD22 antibody, is ongoing at SFGH, but because the antibody is rare the trial has had trouble enrolling volunteers. One patient with lymphoma who didn't respond to standard treatment saw a complete response in this study.

David Straus at Memorial Sloan-Kettering in New York is researching radioimmunotherapy, which uses the antibody method plus a radioactive iodine instead of the ricin toxin. Hopefully, this will be as effective - and, additionally, may be useful in imaging the tumor.

Cytokines are chemicals the body produces to regulate the immune system. One cytokine, IL-6 has been found in lymphomas, so methods of reducing IL-6 levels are being studied, along with ways to increase IL-4 which inhibits IL-6 in the test tube. Two other cytokines may be useful in lymphoma as research expands: IL-2 and IL-12.

A feasibility study will begin soon to expand certain specific lymphoma-related CD8 cells. In this study the researchers will isolate and expand these CD8 cells and put them back into the body, with the hope of added CD8 activation and response to kill lymphoma cells.

According to Kaplan, "things are good right now" in lymphoma research. The NCI (National Cancer Institute) has expressed interest in AIDS malignancy and in this much larger institution, funding is available. Drug companies want to cooperate where development is fastest so they can rush their drugs to the market. Fast proven development means more treatments for people with AIDS. The NCI has better clinical and basic science resources for lymphoma. Also, the AIDS Malignancy Clinical Trial Consortium at the NCI will develop an important tissue bank which will make precious specimens more available for study.

The ACTG has been reluctant and laggard in accepting oncology research in AIDS. Sites for clinical trials are being reduced. The ACTG needs to be influenced by AIDS activists such as the late Andy Zysman from ACT UP/Golden Gate, who made great strides in improving interest in oncology at the ACTG. Unfortunately, the elite infectious disease physicians there monopolize funding and priorities for research. Oncologists and infectious disease physicians mix like oil and water; therefore, the NCI is a better, more productive avenue for research.

Solving some of the systemic problems in AIDS research and in our health care system may never materialize. Nevertheless, through all the hurdles and roadblocks it is promising to see some exciting, new approaches in eradicating lymphoma as we strive to survive AIDS.

For more information on lymphoma order The Lymphoma Project Report, written by Michael Marco from Treatment Action Group in New York. It's free for people with AIDS/$10 for others - call (212) 873-9044.

ACTion UPdate

Does your doctor measure the amount of HIV in your body?

* HIV PCR and bDNA tests measure the amount of HIV in the blood.

* As a thermometer is used for measuring fever, these tests measure if you have a low-level HIV infection or a higher "life-threatening" viral load.

* Without the tests it's a hit and miss in treatment.

* The result is wasted money on poorly managed care and death for people with AIDS.

If you only had a fever!

If you have not received these tests from your insurer or healthcare provider, please call (415) 789-7838 and we will help. (The number was incorrectly reported last week; did everyone enjoy the sale?)

ACT UP Golden Gate meets every Tuesday at 7:30 p.m. at 592 Castro Street, upstairs.

950704
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