MYC/BCL6 DOUBLE HIT LYMPHOMA NEGATIVE FOR T(3;8) BCL6::MYC FUSION IS ASSOCIATED WITH INFERIOR SURVIVAL, IN CONTRAST WITH T(3;8) POSITIVE PSEUDO‐DOUBLE HIT LYMPHOMA

Abstract

Introduction: A small proportion of large B cell non-Hodgkin lymphoma (NHL) has MYC and BCL6 rearrangements, detectable by fluorescence in-situ hybridisation (FISH) break-apart probes. There are conflicting reports on the prognosis of this group. A proportion of them have a single t(3;8) BCL6::MYCtranslocation which accounts for both break-apart probe results. The prognostic significance of this t(3;8) positive group is unknown. Methods: We conducted a retrospective cohort study of cases of high grade B NHL, excluding Burkitt lymphoma, referred to a regional histopathology and FISH laboratory from 14 hospitals in the West Midlands, UK. Cases of MYC/BCL2 double-hit lymphoma without BCL6 rearrangement were excluded. Survival was analysed using univariate and multiple regression with Cox proportional hazards. Results: Data were collected for 106 cases of high grade B cell lymphoma with MYC rearrangements. BCL6 rearrangement by FISH break-apart probe (BCL6r) was seen in 61, of which 19/38 tested with a t(3;8) fusion probe were positive. The four groups, MYC single hit, BCL6r t(3;8) positive, BCL6r t(3;8) negative, and BCL6r t(3;8) untested, were well matched for baseline histological and clinical characteristics. Univariate survival analysis showed that the BCL6r t(3;8) negative group had inferior overall survival (OS) and progression-free survival relative to MYC single hit (hazard ratio (HR) 2.6 for death, p = 0.01), and the association was maintained in a multivariate analysis (HR 3.1, p = 0.01). No significant effect on survival was associated with the BCL6r t(3;8) positive group. Keywords: aggressive B-cell non-Hodgkin lymphoma, diagnostic and prognostic biomarkers, pathology and classification of lymphomas No conflicts of interests pertinent to the abstract.