title: 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.
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.
  
  
  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%.
  
  
  CONCLUSIONS
  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.
authors: Division of Hematology, University of British Columbia, Vancouver, Canada.
authors: Haowei
authors: H
authors: Sun
authors: Centre for Lymphoid Cancer and Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
authors: Kerry J
authors: KJ
authors: Savage
authors: Genome Sciences Centre and Department of Pathology, British Columbia Cancer Agency, Vancouver, Canada.
authors: Aly
authors: A
authors: Karsan
authors: Centre for Lymphoid Cancer and Department of Pathology, British Columbia Cancer Agency, Vancouver, Canada.
authors: Graham W
authors: GW
authors: Slack
authors: Centre for Lymphoid Cancer and Department of Pathology, British Columbia Cancer Agency, Vancouver, Canada.
authors: Randy D
authors: RD
authors: Gascoyne
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Cynthia L
authors: CL
authors: Toze
authors: Centre for Lymphoid Cancer and Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
authors: Laurie H
authors: LH
authors: Sehn
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Yasser
authors: Y
authors: Abou Mourad
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Michael J
authors: MJ
authors: Barnett
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Raewyn C
authors: RC
authors: Broady
authors: Centre for Lymphoid Cancer and Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
authors: Joseph M
authors: JM
authors: Connors
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Donna L
authors: DL
authors: Forrest
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Centre for Lymphoid Cancer and Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Alina S
authors: AS
authors: Gerrie
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Donna E
authors: DE
authors: Hogge
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Sujaatha
authors: S
authors: Narayanan
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Thomas J
authors: TJ
authors: Nevill
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Stephen H
authors: SH
authors: Nantel
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Maryse M
authors: MM
authors: Power
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: Heather J
authors: HJ
authors: Sutherland
authors: Centre for Lymphoid Cancer and Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
authors: Diego
authors: D
authors: Villa
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada.
authors: John D
authors: JD
authors: Shepherd
authors: Division of Hematology, University of British Columbia, Vancouver, Canada; Leukemia/BMT Program of British Columbia, Vancouver General Hospital, Vancouver, Canada. Electronic address: ksong@bccancer.bc.ca.
authors: Kevin W
authors: KW
authors: Song
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D015321:Gene Rearrangement; D019254:Genes, bcl-2 / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide; D008727:Methotrexate
keywords: Aggressive B-cell lymphoma; BCLU; Double-hit lymphoma; Magrath protocol; allotransplant