Outcome of Patients With Non-Hodgkin Lymphomas With Concurrent MYC and BCL2 Rearrangements Treated With CODOX-M/IVAC With Rituximab Followed by Hematopoietic Stem Cell Transplantation

Clin Lymphoma Myeloma Leuk. 2015 Jun;15(6):341-8. doi: 10.1016/j.clml.2014.12.015. Epub 2015 Jan 3.

Abstract

Background: Double-hit lymphoma is characterized by the presence of concurrent MYC (myelocytomatosis oncogene) and BCL2 (B-cell lymphoma 2) gene rearrangements. Prognosis is poor with standard chemoimmunotherapy. Since 2003, the British Columbia Cancer Agency has used CODOX-M/IVAC+R (cyclophosphamide, vincristine, doxorubicin, methotrexate, cytarabine, ifosfamide, and etoposide, combined with rituximab) followed by consolidative hematopoietic cell transplantation as definitive treatment for double-hit lymphoma.

Patients and methods: A retrospective review of the survival outcomes of patients with double-hit lymphoma treated at our institution was conducted. Thirty-two patients diagnosed with non-Hodgkin lymphoma with concurrent MYC and BCL2 translocations from 2003 to 2013 were identified. Cases with MYC or BCL2 amplification and those with overexpression in immunohistochemistry analysis were excluded.

Results: Median age at diagnosis was 53.0 years (range, 35.5-70.9 years), 23 (72%) were male, and 30 (94%) had stage III to IV disease. CODOX-M/IVAC+R was administered in 25 (78%) patients and 20 (80%) achieved a partial remission or better, of which 9 (36%) had a complete remission. Nineteen of the 32 (59%) patients underwent upfront hematopoietic cell transplantation. At a median follow-up of living patients of 26.4 months, 14 (44%) were alive in remission, 15 (47%) died, and 3 (9%) were alive in relapse. The 2-year progression-free survival (PFS) and overall survival (OS) of all patients were 41% and 53%, respectively. The sixteen patients treated with CODOX-M/IVAC+R followed by hematopoietic cell transplantation had a 2-year PFS of 60% and 2-year OS of 82%.

Conclusion: Patients with double-hit lymphoma treated with CODOX-M/IVAC+R followed by hematopoietic cell transplantation can achieve durable remissions, although disease progression before transplantation remains a significant problem.

Keywords: Aggressive B-cell lymphoma; BCLU; Double-hit lymphoma; Magrath protocol; allotransplant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Gene Rearrangement*
  • Genes, bcl-2 / genetics*
  • Genes, myc / genetics*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Ifosfamide / administration & dosage
  • Lymphoma, Non-Hodgkin / genetics*
  • Lymphoma, Non-Hodgkin / pathology
  • Lymphoma, Non-Hodgkin / therapy*
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Retrospective Studies
  • Rituximab / administration & dosage
  • Survival Rate
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Cytarabine
  • Rituximab
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Ifosfamide
  • Methotrexate

Supplementary concepts

  • ANAVACYM protocol
  • IVAC protocol