CHICAGO — The incidence of multicentric Castleman's disease is increasing among patients with human immunodeficiency virus, including those who have access to highly active antiretroviral therapy, Mark Bower, Ph.D., reported in a poster at the annual meeting of the American Society of Clinical Oncology.
Also called angiofollicular or giant lymph node hyperplasia, multicentric Castleman's disease is an atypical lymphoproliferative disorder characterized by the growth of tumors in lymph node tissue. It is causally related to infection with human herpesvirus-8 (HHV-8), and patients are at increased risk of developing a malignancy, such as non-Hodgkin's lymphoma.
In a prospective cohort of nearly 10,997 HIV-positive patients with more than 56,000 patient years of follow-up, Dr. Bower and his coauthors calculated that the overall event rate for multicentric Castleman's disease was 4.3 per 10,000 years of patient follow-up. They reported:
▸ From 1983 to 1996 (the era before highly active antiretroviral therapy [HAART]) the incidence was 2.3 per 10,000 years of patient follow-up.
▸ From 1997 to 2001 (the initial HAART era) the incidence was 2.8 per 10,000 years of patient follow-up.
▸ From 2002 to 2007 (the HAART era) the incidence was 8.3 per 10,000 years of patient follow-up.
The increase over time was significant, but was not associated with gender or prior AIDS, noted Dr. Bower of Chelsea and Westminster Hospital, London. In contrast, the incidence of Kaposi's sarcoma (also causally related to infection with HHV-8) is greater in men, and has decreased with improved immune function and HAART availability.
For the study, plasma HHV-8 DNA levels were measured in 24 HIV-positive patients with newly diagnosed multicentric Castleman's disease, 72 with newly diagnosed Kaposi's sarcoma, 74 with newly diagnosed lymphoma, and in 53 HIV-positive controls with none of these diagnoses.
On multivariate analysis, increased risk of multicentric Castleman's disease was associated with nadir CD4 cell count above 200/mm
A higher proportion of patients with multicentric Castleman's disease had detectable plasma HHV-8 DNA levels at diagnosis, compared with Kaposi's sarcoma patients and lymphoma patients (83% vs. 35% and 3%, respectively). The levels also were higher in patients with newly diagnosed multicentric Castleman's disease (41,000 copies/mL), compared with Kaposi's sarcoma patients (3,500 copies/mL).
In an additional analysis involving the three main HAART drug classes, only nucleoside reverse transcriptase inhibitors were associated with decreased incidence of multicentric Castleman's disease.
The incidence of multicentric Castleman's disease is increasing despite the availability of HAART, and it appears that comparatively well-preserved immune function, increased age, nonwhite race, a short known duration of HIV infection, and no HAART use predispose HIV patients to development of the disease, according to the investigators.
Multicentric Castleman's disease appears to occur more often in older HIV-positive patients with well-preserved immune function, Dr. Bower noted, adding that the role of HHV-8 appears to be different in this disease and Kaposi's sarcoma.
Additional investigation is required to explore the cause of the increased incidence of this disease, he said.