Surviving Multicentric Castleman's Disease (MCD): Do You Gotta Have HAART?
Aaron J Leifer, Julian Arce, Miles Levin, Quilu Pan, Chih-King Huang, Yungtai Lo, Howard Ratech. Albert Einstein College of Medicine, Bronx, NY; Montefiore Medical Center, Bronx, NY
Background: MCD is a non-neoplastic disorder of unknown etiology that often has a fatal outcome. A high association with human herpes virus 8 (HHV8) in many but not all patients suggests a viral pathogenesis. Because it has been suggested that HAART can be either harmful or beneficial in HIV+ patients with MCD, we retrospectively studied the impact of HHV8 viral load and HAART on survival in a cohort of MCD patients with and without HIV.
Design: HHV8 viral load (VL) was measured in DNA extracted from 147 lymph node or spleen samples using a Q-PCR assay originally developed for plasma (J Clin Microbiol 39:4269, 2001). HHV8 VL values were normalized to a mammalian house-keeping gene, HCK. We scored 6 plasma cell and 6 hyaline-vascular morphologic features of MCD. In addition, we immunohistochemically stained tissue samples for HHV8 latent nuclear antigen (LANA-1). Therapy and clinical outcomes were obtained from hospital records and a public mortality database.
Results: HHV8 VL was detected in lymph nodes or spleens from 13 patients: 8 HIV+ and 5 HIV-. In 1/13 tissue samples, HHV8 could be detected by Q-PCR but not by immunostaining for LANA-1. The median follow-up period was 41 months and the mean age was 54.7 ± 17.7 years. There were 6 deaths and 7 long-term survivors. As expected, age was a poor prognostic indicator (per 5 years, Cox proportional hazard model, HR=1.27, 95% CI [0.99-1.61], p=0.05). Neither the morphologic features of MCD (2 hyaline-vascular type, 11 plasma cell type); nor the lymph node counts of CD3, CD4 or CD8; nor the HHV8 VL predicted survival. Surprisingly, 6/8 HIV+ patients who received HAART survived but 4/5 HIV- individuals who did not receive HAART died (Cox proportional hazard model, HR=0.26, 95% CI [0.05-1.44], p=0.12). Although this did not reach statistical significance, it is a highly suggestive trend given the small sample size. Careful review of the individual drugs administered hinted that nucleoside/tide reverse transcriptase inhibitors (NRTI) might explain the longer survival of HIV+ patients compared to HIV- individuals with MCD.
Conclusions: Unexpectedly in this small retrospective study, there was a trend for HIV+ patients to have a superior survival than HIV- individuals. Although we cannot exclude bias in patient selection, it is possible that HAART therapy, in particular NRTI, could be beneficial for treating MCD. This may warrant a larger prospective investigation.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 150, Tuesday Afternoon