Prognostic value of MYC rearrangement in cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma

BACKGROUND: B-cell lymphoma, Unclassifiable with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, for convenience referred to here as unclassifiable B-cell lymphoma, is a category in the 2008 World Health Organization system used for a group of histologically aggressive neoplasms that are difficult to classify definitively. Currently, there is no established standard therapy for these neoplasms. METHODS: The authors assessed MYC status and correlated it with treatment response and outcome in a group of 52 patients with unclassifiable B-cell lymphoma treated with either a standard DLBCL regimen (R-CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone-related therapy]) or more intensive regimens, such as R-hyper-CVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine). The regimens were selected by the treating clinicians based on the overall clinical and pathological findings. RESULTS: Thirty (58%) unclassifiable B-cell lymphomas had MYC abnormalities (MYC ⁺) including 27 with rearrangement, 2 with amplification, and 1 with both. The MYC ⁺ and MYC ^- groups were similar in their age distribution and International Prognostic Index scores. Progression-free survival of patients with MYC ⁺ unclassifiable B-cell lymphoma treated initially with R-CHOP was significantly worse than patients treated with R-hyper-CVAD (P =.0358). In contrast, for the MYC ^- unclassifiable B-cell lymphoma group, some patients responded to R-CHOP, and others were refractory to R-hyper-CVAD. CONCLUSIONS: MYC aberrations are common in unclassifiable B-cell lymphoma. The presence of MYC aberrations identifies a patient subset that requires more aggressive therapy than R-CHOP. In contrast, MYC ^- unclassifiable B-cell lymphoma patients responded variably to either R-CHOP or aggressive therapy, and the latter showed no survival advantage.