Clinical relevance of MYC/BCL2 expression and cell of origin in patients with diffuse large b-cell lymphoma treated with autologous transplant

Bone Marrow Transplant. 2023 Sep;58(9):1000-1007. doi: 10.1038/s41409-023-02006-3. Epub 2023 May 18.

Abstract

Dual expression of MYC and BCL2 proteins (double-expressor lymphoma [DEL]) as well as cell of origin (COO) are important prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) after conventional chemotherapy. We studied the prognostic impact of DEL and COO in patients with relapsed DLBCL treated with autologous stem cell transplant (ASCT). Three-hundred and three patients with stored tissue samples were identified. Classification was successful in 267 patients: 161 (60%) were DEL/non-double hit (DHL), 98 (37%) were non-DEL/non-DHL, and 8 (3%) were DEL/DHL. Compared to non-DEL/non-DHL, DEL/DHL had worse overall survival while DEL/non-DHL did not significantly differ in overall survival. On multivariable analysis, DEL/DHL, age >60 years, and >2 prior therapies, but not COO, were important prognostic factors for overall survival. When we explored the interaction of COO and BCL2 expression, patients with germinal center B-cell (GCB)/BCL2 (+) had inferior progression-free survival (PFS) compared to GCB/BCL2 (-) patients (HR, 4.97; P = 0.027). We conclude that the DEL/non-DHL and non-DEL/non-DHL subtypes of DLBCL have similar survival after ASCT. The negative impact of GCB/BCL2 (+) on PFS warrants future trials targeting BCL2 after ASCT. The inferior outcomes in DEL/DHL need to be verified in a larger number of patients.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autografts
  • Clinical Relevance*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Lymphoma, Large B-Cell, Diffuse* / therapy
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / therapeutic use
  • Proto-Oncogene Proteins c-myc / analysis
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / therapeutic use

Substances

  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc