Two distinct prognostic groups in advanced-stage Hodgkin lymphoma revealed by the presence and site of bulky disease.

Controversy exists regarding the definition and prognostic significance of bulk in advanced-stage (stage III/IV) Hodgkin lymphoma (ASHL), and bulk location (mediastinum vs other sites) further complicated the setting. This retrospective, multi-institutional study comprised 814 ASHL patients between 2000 and 2010 and aimed to evaluate the significance of bulk in ASHL. End points of interest included progression-free survival (PFS) and overall survival (OS). Covariates included maximum diameter and the site of bulky disease. SmoothHR and Kaplan-Meier analyses were used to assess for an association of PFS and OS with covariates. In the exploratory cohort (n = 683), maximum diameter had no association with PFS and a complex, U-shaped association with all-cause mortality on smoothHR analysis. Using 5 cm as a cutoff for bulk, Kaplan-Meier analyses confirmed the smoothHR results. The site of bulk was incorporated to divide patients into 2 groups. The mediastinal bulk (MB) type had more favorable characteristics than the nonbulky/non-MB (NB/NMB) type on age, histology, and bone marrow involvement (P < .001). The MB type was associated with better OS than the NB/NMB-type on univariable analysis (5-year OS, 92% vs 86%; HR, 0.53; 95% confidence interval, 0.34-0.84; P = .007). These findings persisted in the subgroup treated with chemotherapy alone and were confirmed in an independent validation cohort (n = 131). Our findings indicate that mediastinal bulk was associated with more favorable disease characteristics and improved OS in ASHL, and may be a surrogate of a more favorable biology.