Burkitt lymphoma (BL) is a very aggressive subtype of non-Hodgkin's lymphoma that occurs with higher frequency in patients with HIV/AIDS. Patients with HIV-related BL (HIV-BL) are usually treated with high-intensity, multi-agent chemotherapy regimens. The addition of the monoclonal antibody Rituximab to chemotherapy has also been studied in this setting. The potential risks and benefits of commonly used regimens are reviewed herein, along with a discussion of controversial issues in the practical management of HIV-BL, including concurrent anti-retroviral therapy, treatment of relapsed and/or refractory disease, and the role of stem cell transplantation. 1. Introduction Burkitt lymphoma (BL) is a very aggressive subtype of non-Hodgkin lymphoma (NHL) usually associated with translocation of the MYC oncogene. The World Health Organization (WHO) classification recognizes three clinical variants of BL: sporadic, endemic, and immunodeficiency related [1]. The last of these is particularly common in patients with human immunodeficiency virus (HIV), in whom the lifetime incidence of BL has been estimated at 10–20% [2], and wherein it constitutes an acquired immunodeficiency-syndrome- (AIDS-) defining illness. The difference in clinical variants of BL may be explained by variation in stage of B-cell development at which lymphomagenesis occurs and by a potential relationship with Epstein Barr virus (EBV). It has been shown, for instance, that cases of endemic and AIDS-related BL (both of which are generally EBV related) have considerably highermutation rates than those of sporadic BL; EBV-positive BLs also have higher levels of somatic hypermutation of their variable region heavy chain genes, and evidence of antigen selection (whereas EBV-negative BLs generally fail to show this selection)[3]. These data suggest that EBV-negative BL arises from an early centroblast, while EBV-positive BL arises later in development, likely from a memory B cell or late germinal center B cell. Gene expression signatures of the three variants also appear to be distinct, with differences between endemic and sporadic cases of BL in terms of expression of proteins that influence the oncogenic potential of MYC [4], ectopic expression of which is a near-universal phenomenon in BL. Historically, HIV/AIDS-related BL (HIV-BL) has represented a therapeutic challenge, mainly due to (a) the toxicity involved in treating HIV-positive patients with very intense and immunosuppressive regimens found to be successful in HIV-negative patients with BL, (b) the paucity of data from randomized
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