July 15, 2004
It is clear that HIV infection markedly increases the incidence of non-Hodgkin's lymphoma. In the era before the advent of highly active antiretroviral therapy (HAART), the more advanced the HIV infection, the greater the increase in the incidence of AIDS-related lymphoma (ARL), including systemic ARL (s-ARL) and central nervous system lymphoma (CNL). These were harder to treat and cure, at least partly because the bone marrow damage due to advanced HIV infection did not permit full chemotherapy dosing.
It is less well established that HAART reverses the increase in lymphoma incidence. Even less well explored is the impact of HAART on the prognosis of lymphoma, when it does occur.
Details of This Study
Wolf et al reported on 214 cases of ARL treated at the Johann Wolfgang Goethe University Hospital, in Frankfurt, Germany, between 1981 and 2002. Incidence rates per 1,000 patient-years were calculated during 5 time intervals (Table 1 and Figure 1). The rate of s-ARL peaked at 14.8 cases/1,000 patient-years during the 1991-1994 interval, then fell to 3.7 by 1995-2002.
There was also significantly improved survival in the post-HAART era (Figure 2a). Patients were mostly treated with CHOP (a regimen consisting of cyclophosphamide [Cytoxan, Neosar], doxorubicin [Adriamycin, Rubex], vincristine [Oncovin, Vincasar, Vincrex] and prednisone [Deltasone, Orasone]) and the anti-CD20 monoclonal antibody rituximab (Rituxan). HAART was administered as well. The survival rate was better for patients who had a good response to HAART (viral load <500 copies/mL after 3 months; Figure 2b) and patients who achieved complete remission. As noted in the presentation, but not the abstract, there was no impact of survival on HAART response among those achieving complete remission.
Somewhat paradoxically, the survival rate was better in patients with lower CD4+ cell counts. This probably occurs because lymphomas breaking through a more normal immune system are more potent. Patients developing lymphoma with a low CD4+ cell count profit from the restored immunity that HAART will afford.
Significance for Patients and Clinicians
ARL is becoming a more common initial AIDS-defining illness. This study confirms what we would hope regarding the impact of HAART on HIV-related non-Hodgkin's lymphoma: that the incidence rate is substantially reduced and survival improved. Although the study was purely observational, it also provided support for CHOP and rituximab as appropriate chemotherapy during simultaneous use of HAART.
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