Authors

Adam S. Zayac, The Warren Alpert Medical School Medical School of Brown University
Daniel J. Landsburg, University of Pennsylvania
Mitchell E. Hughes, University of Pennsylvania
Allison M. Bock, Mayo Clinic
Grzegorz S. Nowakowski, Mayo Clinic
Emily C. Ayers, University of Virginia
Mark Girton, University of Virginia
Marie Hu, University of Minnesota
Amy K. Beckman, University of Minnesota
Shaoying Li, The University of Texas MD Anderson Cancer Center
L Jeffrey Medeiros, The University of Texas MD Anderson Cancer Center
Julie E. Chang, University of Wisconsin School of Medicine and Public Health
Adam Stepanovic, University of Wisconsin School of Medicine and Public Health
Habibe Kurt, The Warren Alpert Medical School of Brown University
Jose Sandoval-Sus, Moffitt Cancer Center at Memorial Healthcare System,
M Ali Ansari-Lari, Memorial Healthcare System
Shalin K. Kothari, Yale University School of Medicine
Anna Kress, Yale University School of Medicine
Mina L. Xu, Yale University School of Medicine
Pallawi Torka, Roswell Park Comprehensive Cancer Center
Suchitra Sundaram, Roswell Park Comprehensive Cancer Center
Stephen D. Smith, Fred Hutchinson Cancer Research Center
Kikkeri N. Naresh, University of Washington
Yasmin H. Karimi, University of Michigan Health
Narendranath Epperla, The Ohio State University Comprehensive Cancer Center
David A. Bond, The Ohio State University Comprehensive Cancer Center
Umar Farooq, University of Iowa
Mahak Saad, University of Iowa
Andrew M. Evens, Rutgers Cancer Institute of New Jersey
Karan Pandya, Rutgers Cancer Institute of New Jersey
Seema G. Naik, Penn State Hershey Medical Center
Manali Kamdar, University of Colorado
Bradley Haverkos, University of Colorado
Reem Karmali, Northwestern University
Timothy S. Oh, Northwestern University
Julie M. Vose, University of Nebraska Medical CenterFollow
Heather Nutsch, University of Nebraska Medical CenterFollow
Paul G. Rubinstein, University of Illinois
Amina Chaudhry, University of Illinois
Adam J. Olszewski, The Warren Alpert Medical School Medical School of Brown University

Document Type

Article

Journal Title

Blood Advances

Publication Date

2023

Volume

7

Abstract

In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase >3 × upper limit of normal, and a dual-expressor immunophenotype. Age >60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS.

MeSH Headings

Humans, Middle Aged, Rituximab, Retrospective Studies, Lymphoma, Large B-Cell, Diffuse, Prednisone, Vincristine, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins c-myc, Cyclophosphamide, Doxorubicin, Etoposide, Lactate Dehydrogenases

ISSN

2473-9537

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