Leukemic High Grade B Cell Lymphoma is Associated With MYC Translocation, Double Hit/Triple Hit Status, Transformation, and CNS Disease Risk: The Mayo Clinic Experience

Clin Lymphoma Myeloma Leuk. 2022 Aug;22(8):e815-e825. doi: 10.1016/j.clml.2022.04.009. Epub 2022 Apr 14.

Abstract

Introduction: Leukemic involvement in high grade B cell lymphoma (L-HGBL) is rare and has been sparsely described in the literature. We report our experience in a large single institution multicenter academic setting.

Materials and methods: Medical records of patients with HGBL who received care at Mayo Clinic between 2003 and 2020 were reviewed. L-HGBL was confirmed by peripheral blood smear and flow cytometry with corroboration from tissue and bone marrow biopsy findings.

Results: Twenty patients met inclusion criteria. All patients had significant bone marrow involvement by HGBL. Leukemic involvement presented in 11 of 20 (55%) in the de novo and 9 of 20 (45%) in the relapsed setting. Seven of 20 patients had DLBCL, NOS, 6 of 20 had transformation (t-DLBCL), 3 of 20 had transformed double/triple hit lymphoma (t-DHL/THL), 2 of 20 had double hit lymphoma (DHL), and 2 of 20 had HGBL with intermediate features between DLBCL and Burkitt lymphoma. Nine of 15 patients had MYC translocation. Based on Hans criteria, 11 of 20 had germinal center B-cell (GCB) cell of origin (COO) and 9/20 had non-GCB COO. Five of 11 de novo patients experienced CNS relapse/progression. All de novo patients received anthracycline-based chemoimmunotherapy. Eighteen of 20 patients died of progressive disease. Median overall survival was significantly better in the de novo compared to relapsed group (8.9 months vs. 2.8 months, P = .01). COO, MYC status, DHL/THL status, HGBL subtype, or treatment group did not demonstrate a significant effect on overall survival.

Conclusion: L-HGBL carries a poor prognosis and is associated with MYC translocation, DHL/THL status, transformation, and high CNS risk. Novel therapeutic approaches are needed for L-HGBL.

Keywords: De novo high grade B cell lymphoma; Double hit lymphoma; Relapsed high grade B cell lymphoma; Transformed diffuse large B cell lymphoma.

Publication types

  • Multicenter Study

MeSH terms

  • Burkitt Lymphoma* / genetics
  • Central Nervous System Diseases*
  • Disease Susceptibility
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Translocation, Genetic

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • Proto-Oncogene Proteins c-myc