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Non-Hodgkin Lymphoma
Inferior survival in high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements is not associated with MYC/IG gene rearrangements
Ellen D. McPhail,1 Matthew J. Maurer,2 William R. Macon,1 Andrew L. Feldman,1 Paul J. Kurtin,1 Rhett P. Ketterling,1 Rakhee Vaidya,3 James R. Cerhan,4 Stephen M. Ansell,5 Luis F. Porrata,5 Grzegorz S. Nowakowski,5 Thomas E. Witzig1,5 and Thomas M. Habermann5
1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; 2Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN; 3Department of Hematology and Oncology, Wake Forest Baptist Health, Winston-Salem, NC; 4Department of Health Sciences Research, Mayo Clinic, Rochester, MN and 5Division of Hematology, Mayo Clinic, Rochester, MN, USA
ABSTRACT
High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (double-/triple-hit lymphoma) have an aggres- sive clinical course. We investigated the prognostic value of transformation from low-grade lymphoma, cytological features (high grade versus large cell), MYC rearrangement partners (immunoglobu- lin versus nonimmunoglobulin gene), and treatment. We evaluated 100 adults with double-/triple-hit lymphoma, reviewing cytological fea- tures; cell of origin; and rearrangements of MYC, BCL2, and BCL6 using MYC, BCL2, and BCL6 break-apart and IGH/MYC, IGL/MYC, IGK/MYC, and IGH/BCL2 dual-fusion interphase fluorescence in situ hybridization probes. Outcome analysis was restricted to patients with lymphoma, de novo or at transformation, who received anthracy- cline-based chemotherapy. Among them, 60% had high-grade cyto- logical features; 91% had a germinal center B-cell phenotype, and 60% had a MYC/IG rearrangement. Germinal center B-cell phenotype was associated with BCL2 rearrangements (P<0.001). Mean (95% con- fidence interval) 5-year overall survival was 49% (37%-64%). Transformation from previously treated and untreated low-grade lym- phoma was associated with inferior overall survival (hazard ratio, 2.99; P=0.008). Patients with high-grade cytological features showed a non-significant tendency to inferior outcome (hazard ratio, 2.32; P=0.09). No association was observed between MYC rearrangement partner and overall survival (hazard ratio, 1.00; P=0.99). Compared with patients receiving rituximab, cyclophosphamide, doxorubicin, and vincristine (R-CHOP) and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH- R), patients receiving rituximab, cyclophosphamide, vincristine, dox- orubicin, methotrexate/ifosfamide, etoposide, and cytarabine (R- CODOX-M/IVAC) had a non-significant tendency to better overall survival (hazard ratio, 0.37; P=0.10). In conclusion, high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements had heterogeneous outcomes and MYC/IG rearrangements were not asso- ciated with inferior overall survival.
Introduction
The diagnosis of ‘high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements’ (double-/triple-hit lymphoma, DH/THL) was established in the 2016 revision of the World Health Organization (WHO) classification of lym- phoid neoplasms.1 This category includes all large B-cell lymphomas with
Ferrata Storti Foundation
Haematologica 2018 Volume 103(11):1899-1907
Presented as an abstract and poster at the American Society of Hematology 58th Annual Meeting and Exposition, San Diego, California, USA, December 3-6, 2016.
Correspondence:
mcphail.ellen@mayo.edu
Received: February 7, 2018. Accepted: June 12, 2018. Pre-published: June 14, 2018.
doi:10.3324/haematol.2018.190157
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/11/1899
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