Clinical features and therapy of double-hit and double-expressor lymphomas


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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.

作者简介

E Baryakh

City Clinical Hospital №52 of the Department of Health of Moscow; N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation

Email: ebaryakh@gmail.com
канд. мед. наук, врач-гематолог отд-ния гематологии и высокодозной химиотерапии ГБУЗ ГКБ №52, доц. каф. общей терапии ФДПО ФГБОУ ВО РНИМУ им. Н.И.Пирогова 123182, Russian Federation, Moscow, ul. Pekhotnaia, d. 3; 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1

A Misyurina

Hematology Research Center of the Ministry of Health of the Russian Federation

канд. мед. наук, науч. сотр. науч.-клин. отд-ния химиотерапии гемобластозов ФГБУ ГНЦ 125167, Russian Federation, Moscow, Novyi Zykovskii pr., d. 4

A Kovrigina

Hematology Research Center of the Ministry of Health of the Russian Federation

д-р биол. наук, зав. патологоанатомическим отд-нием ФГБУ ГНЦ 125167, Russian Federation, Moscow, Novyi Zykovskii pr., d. 4

T Obukhova

Hematology Research Center of the Ministry of Health of the Russian Federation

канд. мед. наук, зав. науч.-клин. лаб. кариологии ФГБУ ГНЦ 125167, Russian Federation, Moscow, Novyi Zykovskii pr., d. 4

S Kravchenko

Hematology Research Center of the Ministry of Health of the Russian Federation

канд. мед. наук, зав. науч.-клин. отд-нием химиотерапии гемобластозов ФГБУ ГНЦ 125167, Russian Federation, Moscow, Novyi Zykovskii pr., d. 4

A Magomedova

Hematology Research Center of the Ministry of Health of the Russian Federation

д-р мед. наук, вед. науч. сотр. науч.-клин. отд-ния химиотерапии гемобластозов ФГБУ ГНЦ 125167, Russian Federation, Moscow, Novyi Zykovskii pr., d. 4

B Zingerman

Hematology Research Center of the Ministry of Health of the Russian Federation

зав. отд. информационных технологий ФГБУ ГНЦ 125167, Russian Federation, Moscow, Novyi Zykovskii pr., d. 4

E Misyurina

City Clinical Hospital №52 of the Department of Health of Moscow

канд. мед. наук, рук. гематологической службы ГБУЗ ГКБ №52 123182, Russian Federation, Moscow, ul. Pekhotnaia, d. 3

N Poteshkina

City Clinical Hospital №52 of the Department of Health of Moscow; N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation

д-р мед. наук, проф., зав. каф. общей терапии ФДПО ФГБОУ ВО РНИМУ им. Н.И.Пирогова 123182, Russian Federation, Moscow, ul. Pekhotnaia, d. 3; 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1

M Lysenko

City Clinical Hospital №52 of the Department of Health of Moscow

д-р мед. наук, глав. врач ГБУЗ ГКБ №52 123182, Russian Federation, Moscow, ul. Pekhotnaia, d. 3

A Vorobev

Hematology Research Center of the Ministry of Health of the Russian Federation

акад. РАН, д-р мед. наук, проф., глав. науч. сотр. науч.-клин. отд-ния химиотерапии гемобластозов ФГБУ ГН 125167, Russian Federation, Moscow, Novyi Zykovskii pr., d. 4

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