Advanced Stage Hodgkin’s Lymphoma Has More Aggressive Characteristics but Similar Outcome in HIV-Infected Than in HIV-Negative Patients in the Combination Antiretroviral Therapy Era
Authors: Navarro Jose-Tomas , Sorigue Marc , Xicoy Blanca , Garcia Olga , Baptista Maria Joao , Sancho Juan-Manuel , Mate Jose-Luis , Feliu Evarist , Ribera Josep-Maria 
Published: October 2019

Abstract
Background: In the combination antiretroviral therapy (cART) era the prognosis of HIV-infected patients with Hodgkin’s lymphoma (HL) approaches to that of the HIV-negative population. Treatment of advanced stage HL with ABVD has been shown feasible and effective in HIV patients. However, there is scarce information about the impact of cART on clinical and biological characteristics of HIV-related HL as well as on its prognosis.
Aim: To compare the clinical and biological characteristics and outcome of patients with advanced stage HL treated with ABVD according to HIV-status in the cART era.
Methods: Two groups of patients with advanced stage HL treated with ABVD were studied. The first group consisted of 63 HIV-infected patients diagnosed with HL in the cART era in 15 Spanish hospitals, and the control group included 31 HIV-negative patients diagnosed in the same period in a single institution. Demographic, clinical and biological data were collected, and complete response rate (CRR), disease-free survival (DFS) and overall survival (OS) were calculated. Then, HIV-infected patients were stratified according to whether they started cART therapy before or concomitantly with chemotherapy. Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. The Cox regression proportional hazards model was used for multivariate analyses. Significance level was established at p<0.05.
Results: The HIV-infected group showed a higher percentage of males (p=0.001), a higher serum LDH level at diagnosis (p=0.002); and non-significantly, worse ECOG performance status (p=0.05) and more extranodal areas affected (p=0.066). However, the percentage of patients with low Hasenclever score (<3 points) was similar in both groups (p=0.794). The most common HL subtype in HIV-negative patients was nodular sclerosis HL (58%) followed by mixed cellularity (26%), while in HIV-infected population the most common subtype was mixed cellularity (40%), followed by nodular sclerosis (29%).
There were no differences in CRR between the two groups (89% in HIV-infected vs. 87% in HIV-negative, p=1). Furthermore, with a median follow-up of 8.7 years, there were no differences in OS and DFS: 10-year OS 75% (95%CI, 64%-86%) in HIV-infected vs. 67% (50%-84%) in HIV-negative (p=0.674); 10-year DFS 74% (60%-88%) in HIV-infected vs. 64% (42%-86%) in HIV-negative (p=0.196). The only variable associated with a worse OS in the entire series was elevated serum LDH at diagnosis (p=0.047). Low Hasenclever score was not a prognostic factor for OS. No variable was associated with DFS.
In the HIV-infected group, CD4+ cell count at diagnosis (<200/µL vs. >=200/µL) and undetectable viral load were not associated with different CRR (p=0.688 and 0.188, respectively). Furthermore, no lymphoma-related variables were associated with DFS or OS.
Patients who started cART simultaneously (s-cART) with chemotherapy and those who started it previously (p-cART) were comparable in their baseline characteristics except for viral load (undetectable in 50% of patients in the p-cART group vs. 0% in the s-cART group, p=0.001), whereas there were no differences in CD4+ cell count at diagnosis. The prognosis of the 2 groups was similar in terms of CRR and DFS, but s-cART patients showed a trend towards a better OS: 10-year OS 70% (95%CI, 57-83%) in p-cART vs. 92% (77-100%) in s-cART, p=0.072).
Conclusion: Advanced stage HL is still associated with more aggressive features in HIV-positive than HIV-negative patients in the cART era. However, HIV infection is no longer a negative prognostic factor in patients with HL treated with ABVD.
This work was supported in part by grants EC11-041 and RD12/0036/0029 RTICC from “Instituto Carlos III” Spain and 2014 SGR225 (GRE) from Generalitat de Catalunya, and by Josep Carreras International Foundation.

Disclosures
No relevant conflicts of interest to declare.