Gray zone lymphoma with features intermediate between classical hodgkin lymphoma and diffuse large B-cell lymphoma: Characteristics, outcomes, and prognostication among a large multicenter cohort.

Publication Type:

Journal Article


American journal of hematology (2015)


Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease. We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients treated across 19 North American centers. Forty-three percent of patients presented with mediastinal disease (MGZL), while 57% did not (NMGZL). NMGZL patients were older ((50 versus 37 years,) (P) (=0.0001); more often had) bone marrow involvement (19% versus 0%, P=0.001); >1 extranodal site (27% versus 8%, P=0.014); and advanced stage disease (81% versus 13%, respectively, P=0.0001); but less bulk (8% versus 44%, respectively, P=0.0001). Common frontline treatments were cyclophosphamide-doxorubicin-vincristine-prednisone +/- rituximab (CHOP+/-R) 46%, doxorubicin-bleomycin-vinblastine-dacarbazine +/- rituximab (ABVD+/-R) 30%, and dose-adjusted etoposide-doxorubicin-cyclophosphamide-vincristine-prednisone-rituximab (DA-EPOCH-R) 10%. Overall and complete response rates for all patients were 71% and 59%, respectively; 33% had primary refractory disease. At 31-month median follow-up, 2-year progression-free survival (PFS) and overall survival rates were 40% and 88%, respectively. Interestingly, MGZL outcomes appeared similar compared with NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival. Additionally, patients treated with ABVD+/-R had markedly inferior 2-year PFS (22% versus 52%, P=0.03) compared with DLBCL-directed therapy (CHOP+/-R and DA-EPOCH-R), which persisted on Cox regression (HR 1.88, 95%CI 1.03-3.83, P=0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (HR 0.35, 95%CI 0.18-0.69, P=0.002). Collectively, GZL is a heterogeneous and likely more common entity that includes non-mediastinal presentation, while outcomes appear superior when treated with a rituximab-based, DLBCL-specific regimen. This article is protected by copyright. All rights reserved.