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Outcomes of HIV-associated Hodgkin lymphoma in the era of antiretroviral therapy
Published by François RAFFI

Updated: 1 May, 2016

Olszewski AJ et al. AIDS. 2016 Mar 13;30(5):787-96.

Clinical series suggest favorable outcomes of HIV-associated Hodgkin lymphoma, in conflict with population-based statistics. The objective was to investigate the proportion of Americans who received curative chemotherapy for this disease, and compare their survival with HIV-negative cases using population data.

We selected cases of HIV-associated Hodgkin lymphoma diagnosed in 2004–2012 from the National Cancer Data Base (NCDB). Factors associated with receipt of chemotherapy were analyzed by logistic regression. Overall survival was compared in proportional hazard models adjusting for available confounding factors.

Among 43 935 patients with classical Hodgkin lymphoma recorded in the NCDB between 2004 and 2012, 2090 (5%) were HIV-positive.

HIV-positive patients were on average older, primarily in the 40 to 59-year-old group, with a predominance of men and a significantly higher proportion of white Hispanic or black race (In 2012, 49% of HIV-positive patients were black, and 15% were Hispanic).

Two-thirds of HIV-positive patients had advanced-stage Hodgkin lymphoma, and most had B-symptoms – in reverse of proportions observed within the HIV-negative group. HIV-positive Hodgkin lymphoma was also more frequently extranodal in origin, with most frequent sites being bone marrow (46% of extranodal cases), gastrointestinal tract (28%) and head and neck mucosa (13%).

Among the 2090 HIV-positive patients, 81% received chemotherapy (12% in combination with radiation), 13% received any radiation therapy, and 16% received no treatment for their lymphoma. The proportions treated with chemotherapy and radiation were significantly lower compared with the HIV-negative population (87, 31 and 9%, respectively, all P<0.00001).

Advanced age, male sex, nonwhite race, poor socioeconomic status (no health insurance, or living in areas with the lowest median income), and undetermined histologic subtype were associated with higher risk of not receiving chemotherapy.

With median follow-up of 51 months (interquartile range, 30 to 72 months), unadjusted 5-year overall survival for HIV-positive Hodgkin lymphoma was 66% (95% CI, 64– 68%), significantly lower than for HIV-negative patients (80%, 95% CI, 79–80%). Stratified by stage, these estimates among HIV-positive patients were 86% (CI, 81–90%) for 'early favorable' (stage I/IIA), 71% (CI, 64–76%) for 'early unfavorable' (stage I/IIB), and 60% (CI, 57–63%) for advanced stage disease. Among HIV-negative patients, they were 89% (CI, 89–90%), 84% (CI, 83–85%), and 70% (CI, 69–70%), respectively. Among patients who received chemotherapy, HIV-positive status was not significantly associated with higher mortality in classical histologic subtypes, including nodular sclerosis (hazard ratio, HR, 1.08; 95% confidence interval, CI, 0.88–1.33) and mixed cellularity (HR, 1.06; 95% CI, 0.80–1.40). In contrast, prognosis remained significantly worse for cases with undetermined histology (HR, 1.56; 95% CI, 1.31–1.85), suggesting a more aggressive biology or other high-risk characteristics in this subgroup.

Worse survival statistics for HIV-associated Hodgkin lymphoma are driven by lower rates of chemotherapy administration. The disparity in treatment delivery needs attention. The fact that survival with active treatment is not influenced by HIV status in patients with classical histologic subtypes of Hodgkin lymphoma underscores the need for an aggressive approach to obtain an adequate diagnostic sample and to deliver curative therapy, but also for adequate supportive care to assure its safety.

Conclusion : A majority of HIV-positive patients in the current era appear to have the favorable nodular sclerosis morphology and should not miss the opportunity of upfront cure. Those with excellent immune function should potentially not be excluded from the upcoming clinical trials involving immunotherapy or checkpoint inhibitors, as had been previously advocated. Patients with undetermined histology require particular attention due to worse prognosis and high risk of non-treatment, and may be targeted by novel, alternative approaches.