title: 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.
abstract: 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 (MGZL). We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients recently treated across 19 North American centers. Forty-three percent of patients presented with MGZL, whereas 57% had non-MGZL (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%, P = 0.0001); but they had less bulk (8% versus 44%, P = 0.0001), compared with MGZL patients. 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, outcomes in MGZL patients seemed similar compared with that of NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival for all patients. 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 (hazard ratio, 1.88; 95% confidence interval, 1.03-3.83; P = 0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (hazard ratio, 0.35; 95% confidence interval, 0.18-0.69; P = 0.002). Collectively, GZL is a heterogeneous and likely more common entity and often with nonmediastinal presentation, whereas outcomes seem superior when treated with a rituximab-based, DLBCL-specific regimen.
authors.affiliation: Tufts Medical Center, Boston, Massachusetts.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Evens
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kanakry
authors.affiliation: Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.affiliation: Tufts Medical Center, Boston, Massachusetts.
authors.forename: Athena
authors.initials: A
authors.lastname: Kritharis
authors.affiliation: Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Feldman
authors.affiliation: Quantitative Health Sciences, The University of Massachusetts (UMASS), Worcester, Massachusetts.
authors.forename: Aimee
authors.initials: A
authors.lastname: Kroll
authors.affiliation: Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Abramson
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Petrich
authors.affiliation: Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Hernandez-Ilizaliturri
authors.affiliation: Hematology/Oncology, UMASS, Massachusetts.
authors.forename: Zeina
authors.initials: Z
authors.lastname: Al-Mansour
authors.affiliation: Loyola University Medical Center, Maywood, Illinois.
authors.forename: Camille
authors.initials: C
authors.lastname: Adeimy
authors.affiliation: Ohio State University, Columbus, Ohio.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hemminger
authors.affiliation: Washington University School of Medicine, St Louis, Missouri.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
authors.affiliation: Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Anthony
authors.initials: A
authors.lastname: Mato
authors.affiliation: Case Western Reserve University, Cleveland, Ohio.
authors.forename: Paolo F
authors.initials: PF
authors.lastname: Caimi
authors.affiliation: Stanford University, Palo Alto, California.
authors.forename: Ranjana H
authors.initials: RH
authors.lastname: Advani
authors.affiliation: Tufts Medical Center, Boston, Massachusetts.
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Klein
authors.affiliation: The University of Chicago, Chicago, Illinois.
authors.forename: Chadi
authors.initials: C
authors.lastname: Nabhan
authors.affiliation: The University of Chicago, Chicago, Illinois.
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: University of Miami School of Medicine, Miami, Florida.
authors.forename: Jesus C
authors.initials: JC
authors.lastname: Fabregas
authors.affiliation: University of Miami School of Medicine, Miami, Florida.
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
authors.affiliation: Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Fenske
authors.affiliation: University of Rochester, Rochester, New York.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.affiliation: University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.affiliation: Ohio State University, Columbus, Ohio.
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Blum
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D003520:Cyclophosphamide; D004317:Doxorubicin / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005047:Etoposide; D005260:Female; D006689:Hodgkin Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008482:Mediastinum / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011241:Prednisone; D011379:Prognosis; D012189:Retrospective Studies; D000069283:Rituximab; D016019:Survival Analysis; D014750:Vincristine
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone