Response to HAART Predicts Outcome of Lymphoma

SEATTLE—A response to highly active antiretroviral therapy (HAART) independently predicts the outcome of AIDS-related lymphoma, underscoring the importance of giving HIV-positive patients this therapy whenever possible, Christian Hoffmann, MD, of the University of Kiel, Germany, said at the 9th Conference on Retroviruses and Opportunistic Infections (abstract 619W).

Previous studies have yielded conflicting findings about the effect of HAART on the survival of patients with AIDS-related lymphoma, Dr. Hoffman said. Recently, he and his colleagues found that HAART dramatically improves the survival of patients with AIDS and primary central nervous system lymphoma (AIDS 15:2119-2127, 2001). Nonetheless, few studies have looked at associations between the survival of HIV-infected patients with lymphoma and the actual receipt and effectiveness of both HAART and curative lymphoma regimens.

"Due to the poor prognosis of AIDS patients with lymphoma before HAART, many patients and/or physicians possibly might have shown a therapeutic nihilism even after 1996 when HAART became available. Therefore, in studying these patients, one should consider whether they really received HAART and chemotherapy or not, and, if yes, if the HAART and chemotherapy were successful or not," he said.

Dr. Hoffmann and his colleagues analyzed clinical and laboratory predictors of survival in a cohort of 221 patients diagnosed with AIDS-related lymphoma between 1990 and 2001 and treated with chemotherapy or radiation therapy. In 13% of patients, the lymphoma was Hodgkin’s disease. At the time of diagnosis of lymphoma, the patients’ median CD4 count was 140/µL, and AIDS-defining events had occurred in 33%.

During follow-up, 32% of 104 evaluable patients received and had a response to HAART (an increase in the CD4 cell count of more than 100/µL and/or at least one viral load of less than 500 copies/mL within 2 years of diagnosis of AIDS-related lymphoma), and 59% of patients in the entire cohort who received polychemotherapy had a complete remission (an absence of measurable disease for at least 4 weeks on CT scans).

In multivariate analysis, the risk of mortality was reduced significantly in patients with a response to HAART (relative hazard, 0.30) and in patients with a complete remission (vs partial remission or progression) of their lymphoma (relative hazard, 0.26). The risk of mortality was increased in patients with a prior AIDS-defining event (relative hazard, 1.93) and in those with extranodal (vs nodal) manifestations of lymphoma (relative hazard, 2.92).

In contrast, factors historically associated with poor survival of AIDS-related lymphoma (low CD4 cell count, elevated lactate dehydrogenase level, advanced stage, B symptoms, and others) were not significantly associated with mortality in multivariate analysis.

The 2-year survival was 38%. Survival was significantly improved in patients with both a complete remission and a HAART response, with a 2-year survival of 89%. Furthermore, the response to HAART provided a significant prognostic benefit even in the subset of patients with a complete remission and a baseline CD4 cell count of greater than 150/µL (relative hazard of death for patients with HAART response, 0.14).

Summing up the prognostic impact of the combination of a HAART response and complete remission, Dr. Hoffmann said, "If an HIV-positive patient with lymphoma receives chemotherapy and HAART, and if both are successful, then the patient has a prognosis that possibly does not really differ from that of HIV-negative patients with lymphoma."

Dr. Hoffman cited several possible reasons why HAART efficacy has overshadowed historical risk factors for the prediction of outcome of AIDS-related lymphoma. "I think that the success of HAART is not only important in avoiding AIDS-defining illnesses but also in avoiding infectious complications during chemotherapy," he said. "And, last but not least, I would speculate that, at least in some patients, there may be a direct antiproliferative effect of an enhanced immune function."

The findings suggest that it may be time to rethink the traditional approach to treating patients with AIDS-related lymphoma, Dr. Hoffmann noted. "The approach of treating these patients less aggressively than other HIV-infected patients (regarding HAART) or than uninfected patients with lymphoma (regarding chemotherapy) may be inappropriate," he said.

Based on the findings, Dr. Hoffmann offered some recommendations for physicians treating HIV-positive patients with lymphoma. "If the performance status allows any treatment, then try both HAART and chemotherapy," he said. "Even in the presence of several risk factors . . . use a curative chemotherapy regimen and start/intensify/continue HAART. Whenever possible, don’t use palliative chemotherapy regimens since there is a chance to cure lymphoma even in patients with advanced disease."