CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study

Shimin Hu, Zijun Y Xu-Monette, Aarthi Balasubramanyam, Ganiraju C Manyam, Carlo Visco, Alexander Tzankov, Wei-min Liu, Roberto N Miranda, Li Zhang, Santiago Montes-Moreno, Karen Dybkær, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L Richards, Eric D Hsi, William W L Choi, J Han van Krieken, Qin HuangJooryung Huh, Weiyun Ai, Maurilio Ponzoni, Andrés J M Ferreri, Xiaoying Zhao, Jane N Winter, Mingzhi Zhang, Ling Li, Michael Møller, Miguel A Piris, Yong Li, Ronald S Go, Lin Wu, L Jeffrey Medeiros, Ken H Young

Research output: Contribution to journalJournal articleResearchpeer-review

197 Citations (Scopus)

Abstract

CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD30 expression in DLBCL is unknown. Here we report that CD30 expression is a favorable prognostic factor in a cohort of 903 de novo DLBCL patients. CD30 was expressed in ∼14% of DLBCL patients. Patients with CD30(+) DLBCL had superior 5-year overall survival (CD30(+), 79% vs CD30(-), 59%; P = .001) and progression-free survival (P = .003). The favorable outcome of CD30 expression was maintained in both the germinal center B-cell and activated B-cell subtypes. Gene expression profiling revealed the upregulation of genes encoding negative regulators of nuclear factor κB activation and lymphocyte survival, and downregulation of genes encoding B-cell receptor signaling and proliferation, as well as prominent cytokine and stromal signatures in CD30(+) DLBCL patients, suggesting a distinct molecular basis for its favorable outcome. Given the superior prognostic value, unique gene expression signature, and significant value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30(+) DLBCL as a distinct subgroup of DLBCL.
Original languageEnglish
JournalBlood
Volume121
Issue number14
Pages (from-to)2715-24
Number of pages10
ISSN0006-4971
DOIs
Publication statusPublished - 4 Apr 2013

Keywords

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD30
  • Antineoplastic Agents
  • Antineoplastic Combined Chemotherapy Protocols
  • Cyclophosphamide
  • Disease-Free Survival
  • Doxorubicin
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma, Large B-Cell, Diffuse
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prednisone
  • Prognosis
  • Survival Analysis
  • Transcriptome
  • Treatment Outcome
  • Vincristine

Fingerprint

Dive into the research topics of 'CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study'. Together they form a unique fingerprint.

Cite this