Rearrangement ofMYCIs Associated With Poor Prognosis in Patients With Diffuse Large B-Cell Lymphoma Treated in the Era of Rituximab

Abstract

Purpose Rearrangement of MYC occurs in a proportion of diffuse large B-cell lymphomas (DLBCL), where they may be associated with an adverse clinical outcome. The aim of this study was to determine the frequency of MYC translocations in DLBCL and their prognostic impact in the era of cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (CHOP-R) therapy. Patients and Methods Three hundred three patients with previously untreated DLBCL, with no evidence of underlying follicular lymphoma, were investigated using immunohistochemistry and interphase fluorescent in situ hybridization for MYC, BCL6, and t(14;18)/BCL2 rearrangements. All patients (median age, 71.1 years; range, 23 to 96 years) were treated when CHOP-R was standard therapy for DLBCL and observed for a maximum of 4 years. Overall survival (OS) at 3 years was 49% (95% CI, 42% to 56%). Results MYC rearrangements were demonstrated in 35 (14%) of 245 biopsies with data available. Of these, 26 (74%) also had a t(14;18), 10 (26%) were BCL6 and MYC rearranged, and seven had all three abnormalities. Only age, International Prognostic Index, and MYC rearrangement retained prognostic significance in the final model. OS was significantly worse for patients with rearrangement of MYC (survival probability at 2 years = 0.35 in v 0.61 in the nonrearranged group). Conclusion The presence of a MYC rearrangement is a strongly adverse prognostic factor in CHOP-R–treated patients and can be used in combination with patients' age and IPI to accurately predict clinical outcome. In DLBCL, rearrangement of MYC is rarely found as the sole genetic abnormality and the poor prognosis of these patients is likely to reflect a synergistic effect alongside deregulation of BCL6 or BCL2.