Double hit lymphoma: the MD Anderson Cancer Center clinical experience

Br J Haematol. 2014 Sep;166(6):891-901. doi: 10.1111/bjh.12982. Epub 2014 Jun 18.

Abstract

We report our experience with 129 cases of double hit lymphoma (DHL), defined as B-cell lymphoma with translocations and/or extra signals involving MYC plus BCL2 and/or BCL6. All cases were reviewed for histopathological classification. Median age was 62 years (range, 18-85), 84% of patients had advanced-stage disease, and 87% had an International Prognostic Index score ≥2. Fourteen patients (11%) had a history of low-grade follicular lymphoma. MYC translocation was present in 81%, and extra signals of MYC in 25% of patients. IGH-BCL2 translocation was present in 84% and extra signals of BCL2 in 12% of patients. Two-year event-free survival (EFS) rates in all patients and patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and R-HyperCVAD/MA (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate) were 33%, 25%, 67% and 32%, respectively. In patients achieving complete response with initial therapy (n = 71), 2-year EFS rates in patients who did (n = 23) or did not (n = 48) receive frontline stem cell transplantation were 68% and 53%, respectively (P = 0·155). The cumulative incidence of central nervous system involvement was 13% at 3 years. Multivariate analysis identified performance status ≥2 and bone marrow involvement as independent adverse prognostic factors for EFS and OS. Further research is needed to identify predictive and/or targetable biological markers and novel therapeutic approaches for DHL patients.

Keywords: BCL2; BCL6; MYC; double hit lymphoma; prognostic factors.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Central Nervous System Neoplasms / drug therapy
  • Central Nervous System Neoplasms / genetics
  • Central Nervous System Neoplasms / mortality
  • DNA-Binding Proteins / genetics
  • Disease-Free Survival
  • Genes, bcl-2 / genetics
  • Genes, myc / genetics
  • Humans
  • Lymphoma, B-Cell* / drug therapy
  • Lymphoma, B-Cell* / genetics
  • Lymphoma, B-Cell* / mortality
  • Lymphoma, B-Cell* / pathology
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-6
  • Retrospective Studies
  • Translocation, Genetic / genetics
  • Treatment Outcome
  • Young Adult

Substances

  • BCL6 protein, human
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-6