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

Andrew M. Evens, Jennifer A. Kanakry, Laurie H. Sehn, Athena Kritharis, Tatyana Feldman, Aimee Kroll, Randy D. Gascoyne, Jeremy S. Abramson, Adam M. Petrich, Francisco J. Hernandez-Ilizaliturri, Zeina Al-Mansour, Camille Adeimy, Jessica Hemminger, Nancy L. Bartlett, Anthony Mato, Paolo F. Caimi, Ranjana H. Advani, Andreas K. Klein, Chadi Nabhan, Sonali M. SmithJesus C. Fabregas, Izidore S. Lossos, Oliver W. Press, Timothy S. Fenske, Jonathan W. Friedberg, Julie Marie Vose, Kristie A. Blum

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)778-783
Number of pages6
JournalAmerican Journal of Hematology
Volume90
Issue number9
DOIs
StatePublished - Sep 1 2015

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Lymphoma, Large B-Cell, Diffuse
Hodgkin Disease
Lymphoma
Doxorubicin
Vincristine
Prednisone
Cyclophosphamide
Disease-Free Survival
Etoposide
Mediastinal Diseases
Confidence Intervals
Dacarbazine
Vinblastine
Bleomycin
Rituximab
Survival Rate
Bone Marrow
Survival
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Evens, Andrew M.; Kanakry, Jennifer A.; Sehn, Laurie H.; Kritharis, Athena; Feldman, Tatyana; Kroll, Aimee; Gascoyne, Randy D.; Abramson, Jeremy S.; Petrich, Adam M.; Hernandez-Ilizaliturri, Francisco J.; Al-Mansour, Zeina; Adeimy, Camille; Hemminger, Jessica; Bartlett, Nancy L.; Mato, Anthony; Caimi, Paolo F.; Advani, Ranjana H.; Klein, Andreas K.; Nabhan, Chadi; Smith, Sonali M.; Fabregas, Jesus C.; Lossos, Izidore S.; Press, Oliver W.; Fenske, Timothy S.; Friedberg, Jonathan W.; Vose, Julie Marie; Blum, Kristie A.

In: American Journal of Hematology, Vol. 90, No. 9, 01.09.2015, p. 778-783.

Research output: Contribution to journalArticle

Evens, AM, Kanakry, JA, Sehn, LH, Kritharis, A, Feldman, T, Kroll, A, Gascoyne, RD, Abramson, JS, Petrich, AM, Hernandez-Ilizaliturri, FJ, Al-Mansour, Z, Adeimy, C, Hemminger, J, Bartlett, NL, Mato, A, Caimi, PF, Advani, RH, Klein, AK, Nabhan, C, Smith, SM, Fabregas, JC, Lossos, IS, Press, OW, Fenske, TS, Friedberg, JW, Vose, JM & Blum, KA 2015, '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', American Journal of Hematology, vol. 90, no. 9, pp. 778-783. https://doi.org/10.1002/ajh.24082
Evens, Andrew M. ; Kanakry, Jennifer A. ; Sehn, Laurie H. ; Kritharis, Athena ; Feldman, Tatyana ; Kroll, Aimee ; Gascoyne, Randy D. ; Abramson, Jeremy S. ; Petrich, Adam M. ; Hernandez-Ilizaliturri, Francisco J. ; Al-Mansour, Zeina ; Adeimy, Camille ; Hemminger, Jessica ; Bartlett, Nancy L. ; Mato, Anthony ; Caimi, Paolo F. ; Advani, Ranjana H. ; Klein, Andreas K. ; Nabhan, Chadi ; Smith, Sonali M. ; Fabregas, Jesus C. ; Lossos, Izidore S. ; Press, Oliver W. ; Fenske, Timothy S. ; Friedberg, Jonathan W. ; Vose, Julie Marie ; Blum, Kristie A. / 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. In: American Journal of Hematology. 2015 ; Vol. 90, No. 9. pp. 778-783.
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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.",
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T1 - Gray zone lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma

T2 - Characteristics, outcomes, and prognostication among a large multicenter cohort

AU - Evens, Andrew M.

AU - Kanakry, Jennifer A.

AU - Sehn, Laurie H.

AU - Kritharis, Athena

AU - Feldman, Tatyana

AU - Kroll, Aimee

AU - Gascoyne, Randy D.

AU - Abramson, Jeremy S.

AU - Petrich, Adam M.

AU - Hernandez-Ilizaliturri, Francisco J.

AU - Al-Mansour, Zeina

AU - Adeimy, Camille

AU - Hemminger, Jessica

AU - Bartlett, Nancy L.

AU - Mato, Anthony

AU - Caimi, Paolo F.

AU - Advani, Ranjana H.

AU - Klein, Andreas K.

AU - Nabhan, Chadi

AU - Smith, Sonali M.

AU - Fabregas, Jesus C.

AU - Lossos, Izidore S.

AU - Press, Oliver W.

AU - Fenske, Timothy S.

AU - Friedberg, Jonathan W.

AU - Vose, Julie Marie

AU - Blum, Kristie A.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

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