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Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies
Published on: January 7, 2019
Treatment of human immunodeficiency virus-related lymphoma
1Our Lady of Mercy Comprehensive Cancer Center, New York Medical College, Bronx, NY 10466, USA.
Abstract:
In newly diagnosed human immunodeficiency virus (HIV)-positive patients with non-Hodgkin's lymphoma (NHL), standard lymphoma regimens yield approximately a 50% complete response (CR) rate and an overall median survival of < or = 9 months. Treatment results of relapsed patients are extremely poor. Regimens that appear more effective than standard therapy have usually been investigated only in patients with relatively high CD4 counts. An exception is a regimen consisting of a continuous 96-hour infusion of cyclophosphamide, doxorubicin, and etoposide (CDE). A 62% CR rate was achieved in 21 patients with a median CD4 count of 87/microL, and the median overall survival was 18 months. In another study of 25 patients, didanosine (ddI) was added to CDE and was shown to cause less myelosuppression without compromising efficacy. Other studies suggest that highly active antiretroviral therapy (HAART) can be combined with intensive chemotherapy regimens, with improved efficacy attributed to less frequent dosage reduction of chemotherapeutic agents. More recently, autologous and syngeneic bone marrow transplantation have been explored in a handful of patients with acquired immunodeficiency syndrome (AIDS)-related NHL with promising results. Data on whether widespread use of HAART decreases the incidence of HIV-positive NHL are conflicting. Some clues from recent studies suggest we are close to an answer: (1) protease inhibitors significantly improve survival of HIV-positive patients with NHL; (2) only one of eight recent cases of HIV-positive men with NHL received HAART compared with greater than 70% of HIV-positive men free of NHL; and (3) no prior HAART independently predicted for AIDS-related NHL development. On the other hand, Hodgkin's disease may be increasing in frequency in HIV-positive patients as the incidence of NHL declines. It is hypothesized that more effective reconstitution of the immune system with HAART may facilitate the inversion of these incidences. Future prospective studies will hopefully answer these questions.
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