Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2023 Nov 14;7(21):6381-6394.
doi: 10.1182/bloodadvances.2023009731.

High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study

Adam S Zayac  1 , Daniel J Landsburg  2 , Mitchell E Hughes  2 , Allison M Bock  3 , Grzegorz S Nowakowski  3 , Emily C Ayers  4 , Mark Girton  5 , Marie Hu  6 , Amy K Beckman  7 , Shaoying Li  8 , L Jeffrey Medeiros  8 , Julie E Chang  9 , Adam Stepanovic  9 , Habibe Kurt  10 , Jose Sandoval-Sus  11 , M Ali Ansari-Lari  12 , Shalin K Kothari  13 , Anna Kress  13 , Mina L Xu  14 , Pallawi Torka  15 , Suchitra Sundaram  15 , Stephen D Smith  16   17 , Kikkeri N Naresh  18 , Yasmin H Karimi  19 , Narendranath Epperla  20 , David A Bond  20 , Umar Farooq  21 , Mahak Saad  21 , Andrew M Evens  22 , Karan Pandya  22 , Seema G Naik  23 , Manali Kamdar  24 , Bradley Haverkos  24 , Reem Karmali  25 , Timothy S Oh  25 , Julie M Vose  26 , Heather Nutsch  26 , Paul G Rubinstein  27 , Amina Chaudhry  27 , Adam J Olszewski  1
Affiliations
Multicenter Study

High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study

Adam S Zayac et al. Blood Adv. .

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.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: N.E. reports financial support from Pharmacyclics, Seattle Genetics, BeiGene, TG Therapeutics, Novartis, and Incyte. D.J.L. reports financial support from MorphoSys, Calithera, Karyopharm, Epizyme, Curis Inc, ADC Therapeutics, and Triphase. M.E.H. reports financial support from AbbVie, Acerta Pharma, AstraZeneca, Genzyme, and Karyopharm. G.S.N. NanoString, Roche, TG Therapeutics, Zai Lab, Bristol Myers Squibb (BMS)/Celgene, Selvita, Ryvu Therapeutics, MorphoSys US Inc, Kymera Therapeutics, Kite Pharma Inc, Karyopharm, Incyte, Genentech Inc, F. Hoffmann-La Roche Ltd, Daiichi Sankyo Inc, Curis Inc, Celgene Corporation/BMS, Blueprint Medicines Corporation, and Bantam Pharmaceutical. J.S.-S. served on the speaker’s bureu for Seagen and consulted for (advisory boards) TG Therapeutics, AbbVie, ADC therapeutics, Janssen, MorphoSys/Incyte, and MassiveBio. S.K.K. reports financial support from Radyus Research, Karyopharm, and Incyte Pharmaceuticals. M.L.X. reports financial support from Pure Marrow and Blueprint Medicines. P.T. reports financial support from TG Therapeutics, Genentech, ADC Therapeutics, Epizyme, Targeted Oncology, Physician Education Review, and Lilly USA. S.D.S. reports financial support from Portola Pharmaceuticals, Numab Therapeutics AG, Nanjing Pharmaceuticals Co Ltd, MorphoSys, Merck Sharp/Dohme Corp, Kymera Therapeutics, KITE pharma, Karyopharm, Incyte Corporation, Genentech, Epizyme, Enterome, Denovo Biopharma, BeiGene, Bayer, AstraZeneca, ADC Therapeutics, AbbVie, and Viracta Therapeutics. D.A.B. reports financial support from Kite/Gilead, Seagen, Novartis, and Nurix Therapeutics. U.F. reports financial support from Kite, a Gilead Company, MorphoSys, Caribou pharma, and Checkmate Pharma. M.K. reports financial support from AbbVie, AstraZeneca, Celgene/Bristol Myers Squibb, Adaptive Biotechnologies, ADC Therapeutics, BeiGene, Impact Bio, TG Therapeutics, Novartis, Seagen, Celgene, and Genentech. B.H. reports financial support from Viracta Therapeutics and BMS. R.K. reports financial support from Kite, BMS/Celgene, Eusa, Takeda, Pharmacyclics, Genentech/Roche, Karyopharm, BeiGene, Calithera, MorphoSys/Incyte, and AstraZeneca. J.M.V. reports financial support from AstraZeneca, Janssen, Lilly, AbbVie, Johnson & Johnson, Daiichi Sankyo, Pharmacyclics, MorphoSys, and Kite (a Gilead Company). A.J.O. reports financial support from Genmab, Precision Bio, Adaptive Biotechnologies, Celldex, Acrotech Biopharma, Schrodinger, TG Therapeutics, and Genentech. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Clinicopathologic characteristics of HGBL-NOS. (A) Prevalence of the most common immunophenotypes with or without MYC rearrangement (only phenotypes with n ≥ 2 are shown); (B) prevalence of MYC and/or BCL2 alterations, via FISH, in morphologic subtypes; distribution of characteristics based on panel B tumor morphology and (C) cell of origin determined via immunohistochemistry (P values from Fisher exact test).
Figure 2.
Figure 2.
Survival outcomes in HGBL-NOS. (A) PFS for all patients and (B) based on the tumor morphology; (C-D) analogous curves for OS; P values were obtained using log-rank test.
Figure 3.
Figure 3.
Biologic risk factors in HGBL-NOS. PFS based on (A) the cell of origin via immunohistochemistry, (B) DEL phenotype (MYC and BCL2 expression via immunohistochemistry), (C) presence of MYC alterations via FISH, and (D) presence of TP53 alterations (by sequencing or p53 IHC); (E-H) analogous curves for OS; P values were obtained using log-rank test (log-rank test for trend as indicated).
Figure 3.
Figure 3.
Biologic risk factors in HGBL-NOS. PFS based on (A) the cell of origin via immunohistochemistry, (B) DEL phenotype (MYC and BCL2 expression via immunohistochemistry), (C) presence of MYC alterations via FISH, and (D) presence of TP53 alterations (by sequencing or p53 IHC); (E-H) analogous curves for OS; P values were obtained using log-rank test (log-rank test for trend as indicated).
Figure 4.
Figure 4.
Survival outcomes in HGBL-NOS based on the first-line therapy. (A) PFS among patients treated with R-CHOP, DA-EPOCH-R, R-CODOX-M/IVAC, or R-hyperCVAD/MA; P values compare R-CHOP with other (intensive) regimens; (B) PFS among patients treated with R-CHOP or DA-EPOCH-R, stratified based on the presence or absence of MYC rearrangement (MYC-R), P values compare MYC-R+ groups treated with R-CHOP or DA-EPOCH-R; (C) PFS among patients with Burkitt-like HGBL-NOS (excluding transformed and PTLD cases) treated with R-CHOP or DA-EPOCH-R; and (D-F) analogous curves for OS.
Figure 4.
Figure 4.
Survival outcomes in HGBL-NOS based on the first-line therapy. (A) PFS among patients treated with R-CHOP, DA-EPOCH-R, R-CODOX-M/IVAC, or R-hyperCVAD/MA; P values compare R-CHOP with other (intensive) regimens; (B) PFS among patients treated with R-CHOP or DA-EPOCH-R, stratified based on the presence or absence of MYC rearrangement (MYC-R), P values compare MYC-R+ groups treated with R-CHOP or DA-EPOCH-R; (C) PFS among patients with Burkitt-like HGBL-NOS (excluding transformed and PTLD cases) treated with R-CHOP or DA-EPOCH-R; and (D-F) analogous curves for OS.
See this image and copyright information in PMC

References

    1. Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022;36(7):1720–1748. - PMC - PubMed
    1. Campo E, Jaffe ES, Cook JR, et al. The international consensus classification of mature lymphoid neoplasms: a report from the Clinical Advisory Committee. Blood. 2022;140(11):1229–1253. - PMC - PubMed
    1. Olszewski AJ, Kurt H, Evens AM. Defining and treating high-grade B-cell lymphoma, NOS. Blood. 2022;140(9):943–954. - PubMed
    1. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–2390. - PMC - PubMed
    1. International Non-Hodgkin's Lymphoma Prognostic Factors Project A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993;329(14):987–994. - PubMed

Publication types

MeSH terms