Castleman's disease is a rare complication of HIV infection. Signs/symptoms of Castleman's disease can include the following:

• swollen lymph nodes
• weight loss
• fever
• swollen liver and/or spleen
• low levels of red blood cells

Castleman's disease is caused by a virus that also causes another AIDS-related disorder -- Kaposi's sarcoma. This virus, called KSHV (Kaposi's sarcoma-associated herpes virus), infects a type of immune cell called B-cells, overstimulating them. These infected B-cells grow abnormally and multiply rapidly, fill up lymph nodes and produce higher-than-normal levels of antibodies. There is no standard treatment for Castleman's disease.

Doctors in Milan, Italy, reported the successful treatment of an HIV positive woman who had Castleman's disease. She was treated with a new anti-cancer therapy that is called Rituxan (rituximab) in North America and Mabthera in Europe. This drug is different from many other anti-cancer therapies in that it consists of antibodies that attack a protein found on B-cells that have turned into tumours.

Study Details

A 52-year-old woman went to the emergency department of a hospital because her symptoms of the past two weeks -- fever, night sweats, fatigue, shortness of breath -- had been growing worse. Her CD4+ cell count was 383 cells and her viral load was below 500 copies. At that time, her anti-HIV therapy consisted of two nukes -- d4T (Zerit, stavudine) and 3TC (lamivudine, Epivir). Analysis of her lymph nodes revealed KSHV-related production of high levels of the chemical messenger interleukin-6 (IL-6).

Therapies Tested

Doctors gave the woman the antiviral drug cidofovir (Vistide) and anti-IL-6 therapy, but this did not help her condition. Their next approach was anti-cancer therapy using the following drugs at eight-week intervals:

• bleomycin
• doxorubicin
• vincristine

Treatment with these three drugs caused a rapid improvement in the woman's Castleman's disease. However, two months after she first entered the hospital her CD4+ count had fallen to 104 cells and her viral load rose to about 15,000 copies, so doctors prescribed the following combination of anti-HIV drugs:

• d4T
• nevirapine (Viramune)
• indinavir (Crixivan)

After four months of this new anti-HIV combination, the woman's viral load fell below the 80 copy mark. She continued to receive chemotherapy every three weeks. After six months of triple chemotherapy, her anti-cancer regimen was changed to intravenous liposomal daunorubicin given every two to four weeks. After four months of this new chemotherapy, CAT scans of her body did not reveal any swelling in her lymph nodes or spleen. Yet, shortly after each cycle of chemotherapy was complete, the following symptoms returned:

• night sweats
• weakness

Along with these symptoms, levels of KSHV in the woman's blood rose. Two years after she first sought medical attention, doctors decided to give her a single intravenous dose of the new anti-cancer drug rituximab. KSHV levels fell to undetectable levels and her symptoms cleared. No side effects were reported and no changes to CD4+ and CD8+ cell counts or viral load were noted.

These results are exciting but further study is needed to find out if rituximab alone can help people with HIV/AIDS recover from Castleman's disease or if pre-treatment with chemotherapy and highly active antiretroviral therapy is needed.

Reference

1. Corbellino M, Bestetti G, Scalamonga C, et al. Long-term remission of Kaposi sarcoma-associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy. Blood 2001;98(12):3473-3475.