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Prepublished online as a Blood First Edition Paper on February 27, 2003; DOI 10.1182/blood-2002-11-3589. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3589v1 101/12/4653    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Little, R. F. Articles by Wilson, W. H. Search for Related Content PubMed PubMed Citation Articles by Little, R. F. Articles by Wilson, W. H. Related Collections Immunobiology Neoplasia Plenary Papers Oncogenes and Tumor Suppressors Gene Expression Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2003, Vol. 101, No. 12, pp. 4653-4659 PLENARY PAPERS Highly effective treatment of acquired immunodeficiency syndrome–related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biology Richard F. Little, Stefania Pittaluga, Nicole Grant, Seth M. Steinberg, Mark F. Kavlick, Hiroaki Mitsuya, Genoveffa Franchini, Martin Gutierrez, Mark Raffeld, Elaine S. Jaffe, Gene Shearer, Robert Yarchoan, and Wyndham H. Wilson From the Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD. The outcome of acquired immunodeficiency syndrome–related lymphomas (ARLs) has improved since the era of highly active antiretroviral therapy, but median survival remains low. We studied dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) with suspension of antiretroviral therapy in 39 newly diagnosed ARLs and examined protein expression profiles associated with drug resistance and histogenesis, patient immunity, and HIV dynamics and mutations. The expression profiles from a subset of ARL cases were also compared with a matched group of similarly treated HIV-negative cases. Complete remission was achieved in 74% of patients, and at 53 months median follow-up, disease-free and overall survival are 92% and 60%, respectively. Following reinstitution of antiretroviral therapy after chemotherapy, the CD4+ cells recovered by 12 months and the viral loads decreased below baseline by 3 months. Compared with HIV-negative cases, the ARL cases had lower bcl-2 and higher CD10 expression, consistent with a germinal center origin and good prognosis, but were more likely to be highly proliferative and to express p53, adverse features with standard chemotherapy. Unlike HIV-negative cases, p53 overexpression was not associated with a poor outcome, suggesting different pathogenesis. High tumor proliferation did not correlate with poor outcome and may partially explain the high activity of dose-adjusted EPOCH. The results suggest that the improved immune function associated with highly active antiretroviral therapy (HAART) may have led to a shift in pathogenesis away from lymphomas of post–germinal center origin, which have a poor prognosis. These results suggest that tumor pathogenesis is responsible for the improved outcome of ARLs in the era of HAART. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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