This project is focused on the clinical study of patients with AIDS-related malignancies. Much of the work is focused on tumors associated with Kaposis sarcoma-associated herpesvirus (KSHV), also called human herpesvirus-8 (HHV-8). This virus is the cause of Kaposis sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castlemans disease (MCD). We are also studying antibody to VEGF (bevacizumab) as a therapeutic agent in KS as well as BAY 43-9007 (sorafineb). Bevacizumab was shown in an initial tril to have clinical activity in about 30% of patients. Sorafineb is of interest because it can downregulate several receptors for VEGF. We have also initiated a trial of bevacizumab in combination with liposomal doxorubicin in patients with severe KS. Most recently, we initiated a trial of pomalidomide in KS. We have initiated a clinical trial to study the natural history of MCD and to explore the treatment of MCD using a combination of AZT and valganciclovir, a pro-drug of ganciclovir as well as several other approaches (including liposomal doxorubicin and rituxuimab). Initial results show that AZT plus ganaiclovir has substantial activity, although relapses are common when used alone. In addition, we are studying other patients with KSHV infection to assess factors that may be linked to malignancy. We are exploring methotrexate-based therapy for primary central nervous system lymphoma (PCNSL). We are also studying infusional chemotherapy as therapy for AIDS-associated lymphoma in collaboration with the Metabolism Branch. We have identified a group of patients with a new KSHV-related syndrome, called KSHV inflammatory cytokine syndrome (KICS), and have just opened a protocol to study this new disease. Finally, as part of this effort, we are collaborating with a number of other investigators to conduct translational studies related to HIV, AIDS-malignancies, and also xenotropic murine leukemia-virus related virus (XMRV).

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
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National Cancer Institute Division of Basic Sciences
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Goncalves, Priscila H; Montezuma-Rusca, Jairo M; Yarchoan, Robert et al. (2016) Cancer prevention in HIV-infected populations. Semin Oncol 43:173-88
Polizzotto, Mark N; Uldrick, Thomas S; Wyvill, Kathleen M et al. (2016) Clinical Features and Outcomes of Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS). Clin Infect Dis 62:730-8
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
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; 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
Venkataraman, Girish; Uldrick, Thomas S; Aleman, Karen et al. (2013) Bone marrow findings in HIV-positive patients with Kaposi sarcoma herpesvirus-associated multicentric Castleman disease. Am J Clin Pathol 139:651-61
Polizzotto, Mark N; Uldrick, Thomas S; Hu, Duosha et al. (2012) Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV-MCD) and the KSHV Inflammatory Cytokine Syndrome. Front Microbiol 3:73
Uldrick, Thomas S; Polizzotto, Mark N; Yarchoan, Robert (2012) Recent advances in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease. Curr Opin Oncol 24:495-505
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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