1. NATURAL HISTORY AND THERAPY OF KSHV INFLAMMATORY CYTOKINE SYNDROME KSHV inflammatory cytokine syndrome (KICS) is a newly recognized syndrome caused by Kaposi sarcoma-associated herpesvirus (KSHV). It is characterized by severe inflammatory symptoms including fevers, wasting, cytopenias, hypoalbuminemia, and hyponatremia, associated in some cases with lymphadenopathy or effusions, without pathological evidence of MCD. Patients with KICS exhibit elevated KSHV viral loads and cytokine dysregulation, with elevations of IL-6, IL-10, and a KSHV-encoded IL-6 homolog, viral IL-6. The primary study objective is to enable intensive study and description of the natural history of KICS. Secondary objectives include assessment in affected persons of KSHV viral loads and cytokine levels, evaluation of tissue pathophysiology, exploration of 18FDG-PET abnormalities, and pilot assessment of response to two therapies: high dose zidovudine/valganciclovir or rituximab/liposomal doxorubicin. 2. POMALIDOMIDE IN KS Kaposi Sarcoma (KS) is an incurable, multicentric angioproliferative tumor that most frequently involves the skin. It is seen most frequently in people with HIV or other forms of immune compromise. Current therapies are limited by toxicities, including cumulative cardiotoxicity, while effective oral agents, agents deliverable in resource-limited settings, and agents deliverable long-term for relapsing disease are all lacking. The primary objective of this study is to: assess the safety, tolerability and pharmacokinetics of pomalidomide in subjects with Kaposi sarcoma, whether HIV associated or not. Secondary objectives include characterization of immunological and virological changes, including cytokine changes and T cell responses, during pomalidomide therapy. 3. IMAGING OF KSHV ASSOCIATED TUMORS Kaposi's sarcoma is a highly vascular tumor. As such, it may provide a good model for the study of angiogenesis-based therapy in cancer. However, there are no standardized techniques now available to assess the effects of anti-angiogenesis therapy on blood flow in KS tissues. The present protocol is written to allow us to explore and gain experience with four promising techniques to examine tumor vasculature and structure in cutaneous KS lesions: a) laser Doppler imaging;b) multi-spectral imaging;c) infrared thermal imaging;and d) optical coherence tomography. The first objective is to assess, in preliminary fashion, non-invasive methods for studying tumor vascularity, structure, and vascular changes in patients with Kaposi's sarcoma using four different imaging techniques. Other objectives are to correlate these techniques to each other and to conventional KS tumor assessment, and to assess the response of these techniques in patients receiving therapy for Kaposi's sarcoma. In addition, we are now correlating these techniques with systemic nuclear imaging using FDG-PET functional imaging. We have shown that this technique is of utility in other KSHV-associated tumors, KSHV-MCD and PEL, and now are extending this work to KS in conjunction with local imaging techniques.

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Bhutani, Manisha; Polizzotto, Mark N; Uldrick, Thomas S et al. (2015) Kaposi sarcoma-associated herpesvirus-associated malignancies: epidemiology, pathogenesis, and advances in treatment. Semin Oncol 42:223-46
Polizzotto, Mark N; Millo, Corina; Uldrick, Thomas S et al. (2015) 18F-fluorodeoxyglucose Positron Emission Tomography in Kaposi Sarcoma Herpesvirus-Associated Multicentric Castleman Disease: Correlation With Activity, Severity, Inflammatory and Virologic Parameters. J Infect Dis 212:1250-60
Aka, Peter V; Kemp, Troy J; Rabkin, Charles S et al. (2015) A multiplex panel of plasma markers of immunity and inflammation in classical kaposi sarcoma. J Infect Dis 211:226-9
Labo, Nazzarena; Miley, Wendell; Marshall, Vickie et al. (2014) Heterogeneity and breadth of host antibody response to KSHV infection demonstrated by systematic analysis of the KSHV proteome. PLoS Pathog 10:e1004046
Polizzotto, Mark N; Uldrick, Thomas S; Yarchoan, Robert (2014) Case 29-2013: An HIV-positive man with dyspnea and skin lesions. N Engl J Med 370:87-8
Shahbazi, Shandiz; Peer, Cody J; Polizzotto, Mark N et al. (2014) A sensitive and robust HPLC assay with fluorescence detection for the quantification of pomalidomide in human plasma for pharmacokinetic analyses. J Pharm Biomed Anal 92:63-8
Uldrick, Thomas S; Polizzotto, Mark N; Aleman, Karen et al. (2014) Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease. Blood 124:3544-52
Polizzotto, Mark N; Uldrick, Thomas S; Wang, Victoria et al. (2013) Human and viral interleukin-6 and other cytokines in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease. Blood 122:4189-98
Kainerstorfer, Jana M; Polizzotto, Mark N; Uldrick, Thomas S et al. (2013) Evaluation of non-invasive multispectral imaging as a tool for measuring the effect of systemic therapy in Kaposi sarcoma. PLoS One 8:e83887
Uldrick, Thomas S; Wyvill, Kathleen M; Kumar, Pallavi et al. (2012) Phase II study of bevacizumab in patients with HIV-associated Kaposi's sarcoma receiving antiretroviral therapy. J Clin Oncol 30:1476-83

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