Targeted Oncolytic Virotherapy and Natural History Study of KSHV-Associated Multicentric Castleman's Disease With Laboratory and Clinical Correlates of Disease Activity
- Multicentric Castleman's disease (MCD) is a rare but lethal Kaposi's sarcoma-associated
herpesvirus (KSHV) associated lymphoproliferative disorder with a median survival of 2
years. It occurs more often in HIV-infected individuals than those without HIV
infection. The poor prognosis is not fully explained by the underlying HIV, as the
HIV-negative cases appear to have no survival advantage over the HIV-positive cohort.
The disease has no defined standard treatment and has not been prospectively studied in
a comprehensive manner.
- KSHV-MCD may provide a model for the development of targeted oncolytic virotherapy or
other pathogenesis-based approaches to viral-associated malignancies. In KSHV-MCD,
viral encoded tyrosine kinase genes appear to be possible targets to exploit in a
virotherapy approach. Specific viral encoded genes appear to convert zidovudine and
ganciclovir (or valganciclovir) into toxic phosphorylated moieties within the
KSHV-infected tumor cells, to specifically target the KSHV-infected cells thus leading
to specific cell death. If successful, this could have direct therapeutic benefit to
patients and also provide a model for further development of this approach in other
- To study and describe the natural history of KSHV-MCD.
- To assess disease activity as reflected by fever, thrombocytopenia, anemia,
neutropenia, and lymphocytopenia, human and viral interleukin-6 levels, C-reactive
protein, and KSHV viral loads.
- To describe how the laboratory pathogenesis-related parameters (especially serum levels
of human and viral interleukin-6) are related to the clinical and hematologic
- Age greater than or equal to 12 years
- Biopsy proven KSHV-associated MCD
- Natural History study
- Inclusion of treatment as needed, with guidelines for preliminary investigation of a
variety of specific treatments of interest
- High-dose zidovudine and ganciclovir
- High-dose zidovudine and ganciclovir and bortezomib
- Rituximab with liposomal doxorubicin followed by interferon-alpha
- Rituximab with EPOCH chemotherapy
Robert Yarchoan, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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