Современная онкология (Dec 2016)
Clinical features and therapy of double-hit and double-expressor lymphomas
Abstract
Purpose. The identifying of the clinical, morphological, immunophenotypic and cytogenetic features of double-hit and double-expressor lymphomas as well as the development of optimal tactics of treatment and evaluation of efficiency of the ASCT were the main purposes of the study. Material and methods. The study included 85 patients: 45 males and 40 females, the median was 46,6 years (15-73). 62 patients with DLBCL and 23 with BCLu were given BL-M-04/ m-NHL-BFM-90 regimes in Hematological Scientific Center and Municipal Clinical Hospital №52, 2001-2015. Results. Stage I was diagnosed in 5 (6%) patients, II - in 13 (15%) patients, III - in 7 (8%) patients, IV - in 60 (71%) patients. Double-hit lymphoma was diagnosed in 6 (7%) patients (5 MYC+/BCL2+, 1 MYC+/BCL6+), single-hit lymphoma was diagnosed in 6 patients. The translocation was detected in 5 of 12 cases t(8;14)(q24;q32), in 1 case of 12 - t(2;8)(p21;q24), in 2 cases of 12 - t(8;22)(q24;q11) (restructuring c-MYC and IGL gene loci have been identified), in 3 cases of 12 - restructuring of c-MYC with non-IG partner [translocation was absent t(8;14)(q24;q32) and restructuring IGK and IGL gene loci], the partner was not identified in one case of translocation with c-MYC gene [restructuring c-MYC gene loci was identified and translocation was absent t(8;14(q24;q32)]. 8 factors had prognostic significance in relation to OS: nosology - BCLu vs DLBCL (p=0.007; RR=4.5), bone marrow lesion (p=0.0004; RR=7.9), B-symptoms (p=0.0002; RR=8.4), BCL2 expression (I=0.01; RR=4.4), MYC/BCL2 coexpression (p=0.017; RR=0.08), double-hit or double-expressor lymphomas (p=0.009; RR=15.1), the absence of rituximab in therapy (p=0.03; RR=0.3), unfulfillment of ASCT (p=0.003; RR=0.06). Two factors were significant in relation to probability of development of recurrence/progression: double-hit or double-expressor lymphomas (p=0.0005; RR=4.0) and IPI (p=0.03; RR=4.9). Conclusions. Thus, complex diagnostic includes the antibody to the BCL2 (clone 124, Dako) and MYC (clone Y69, Epitomics), and the conduct of standard cytogenetic analysis (SCA) and FISH to detect rearrangements of MYC, BCL2, and BCL6 genes in addition to standard immunohistochemical panel for aggressive B-cell lymphomas. It allows not only to establish the correct diagnosis (DLBCL, BCLu or LB), but also to detect the double-hit and double-expressor lymphomas, which require intensive induction with rituximab and high-consolidation ASCT in first remission.
