A Population-Based Study Reveals the Unique Clinical Characteristics and Long-Term Survival of Patients with Gray Zone Lymphoma

Background and objective

Gray zone lymphoma (GZL) is a rare disease entity with pathological features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (HL). Herein, we examined detailed clinical features, outcomes, and prognostic factors of patients with GZL.

Materials and methods

Chemotherapy-treated patients with GZL diagnosed between 2000 and 2018 were selected. Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Cox and Fine-Gray regression models were used to evaluate overall and GZL-specific survival, respectively.

Results

A total of 211 patients were selected. Most patients were aged 55 years or older (51.7%). The lymph node was the most common primary site (85.3%). Patients with nodal primary sites presented more often with B symptoms (P = 0.041) and advanced-stage disease (P < 0.001). The 5-year overall survival (OS) rates and lymphoma-specific death rates of treated GZL patients were 75.1% (95% CI: 69.0%-81.2%) and 20.8% (95% CI: 15.1%-26.5%), respectively. Patients receiving combined radiotherapy had improved OS (P = 0.011) and lymphoma-specific survival (LSS, P = 0.031). Other independent prognostic factors included age, ethnicity and race. Patients who received combined radiotherapy, without B symptoms, Hispanic, and younger than 55 years generally had higher 3-year conditional survival (CS) rates.

Discussion and conclusions

Given its rarity, a relative paucity of clinical data exists describing GZL, and most publications are limited by small sample sizes and heterogeneous results, constraining our ability to better understand the clinical features and outcomes of GZL.

The present study represents the first and largest population-based study of chemotherapy-treated GZL patients with the longest follow-up, improving the generalizability of the results. An age cutoff was set, providing an excellent estimate of the prognosis. Several critical clinical features were identified, contributing to understanding the characteristics of GZL patients. In addition to the conventional survival analysis, a dynamic survival indicator was used to comprehensively investigate the clinical outcomes. It is noteworthy that chemotherapy-treated patients had potential for long-term survival, and patients who received combined radiotherapy had improved OS and LSS. Other significant prognostic factors for survival included age, ethnicity, race, B symptoms and Ann Arbor stage. Recognition of the unique clinical features of GZL and the factors that predict survival will enable clinical decision-making.

Funding

This work was supported by 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYJC21007).

Ethics Statement

Ethical approval is not required for this study because the SEER database is free of any sensitive patient information or identifiers.

Key words

Gray zone lymphoma, clinical characteristics, overall survival, lymphoma-specific survival, conditional survival

No relevant conflicts of interest to declare.