title: MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy.
abstract: Approximately 5% to 10% of diffuse large B-cell lymphomas (DLBCLs) harbor an MYC oncogene rearrangement (MYC+). The prognostic significance of MYC+ DLBCL was determined in an unselected population of patients with newly diagnosed DLBCL treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP). Using a Vysis break-apart fluorescence in situ hybridization probe, 12 of 135 (8.8%) cases of MYC+ DLBCL were identified that had no defining high-risk features. MYC+ DLBCL was associated with an inferior 5-year progression-free survival (66% vs 31%, P = .006) and overall survival (72% vs 33%, P = .016). Multivariate analysis confirmed the prognostic importance of MYC for both progression-free survival (hazard ratio = 3.28; 95% confidence interval, 1.49-7.21, P = .003) and overall survival (hazard ratio = 2.98; 95% confidence interval, 1.28-6.95, P = .011). Cases of MYC+ DLBCL also had a higher risk of central nervous system relapse (P = .023), independent of other risk factors. The diagnosis of MYC+ DLBCL is likely underappreciated; and given the lack of defining risk factors, fluorescence in situ hybridization for MYC rearrangements should be performed in all patients with DLBCL. In the R-CHOP treatment era, MYC+ DLBCLs have an inferior prognosis. Treatment regimens similar to those used in Burkitt lymphoma may be more appropriate in this patient population and need to be prospectively tested.
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, 600 West 10th Ave, Vancouver, BC, Canada V5Z4E6. ksavage@bccancer.bc.ca
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Savage
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Johnson
authors.forename: Susana
authors.initials: S
authors.lastname: Ben-Neriah
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.forename: Pedro
authors.initials: P
authors.lastname: Farinha
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Horsman
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone