Роль транслокаций с участием локусов генов c-MYC/8q24, BCL2/18q21 и/или BCL6/3q27 у больных фолликулярной лимфомой. Ретроспективный анализ данных одноцентрового исследования
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Misyurina A.E., Kravchenko S.K., Kovrigina A.M., et al. The role of translocations involving c-MYC/8q24, BCL2/18q21 and/or BCL6/3q27 genes in patients with follicular lymphoma. Retrospective analysis of single-centre data. Therapeutic Archive. 2019; 91 (7): 52–62. DOI: 10.26442/00403660.2019.07.000070
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Материалы и методы. С 2004 по 2017 г. в ФГБУ «НМИЦ гематологии» Минздрава России наблюдались 12 больных с диагнозом HGBL DH и 6 больных ФЛ с транслокациями с участием локусов генов c-MYC, BCL2 и/или BCL6. Мы выполнили сравнительный ретроспективный анализ клинических характеристик в обеих группах пациентов. В качестве первичных конечных точек оценена частота полных ремиссий (ПР) и прогрессирования заболевания (Прогр), в качестве вторичных – общая (ОВ) и бессобытийная выживаемость (БСВ).
Результаты. У 5 больных с HGBL DH выявлены транслокации с участием локусов генов c-MYC/BCL6, у 7 – c-MYC/BCL2; у 2 с диагнозом ФЛ – c-MYC/BCL2, у 3 – c-MYC/BCL6, у 1 – c-MYC/BCL2/BCL6. Цитологический тип ФЛ представлен ФЛ 3А с бластоидной морфологической картиной в 2 случаях, ФЛ 3В в 4 случаях, 3 из которых имели признаки гистологической трансформации. Больные HGBL DH и ФЛ не имели значимых различий по клиническим характеристикам. Так, большинство из них имели распространенную стадию заболевания, повышенную активность лактатдегидрогеназы, высокую частоту вовлечения экстранодальных областей и костного мозга. Уровень пролиферативной активности Ki-67 был значимо выше у больных HGBL DH (p<0,05). Больные HGBL DH получали терапию по протоколам R-BL-M-04, R-(DA)-EPOCH, CHOP-21±R, больные ФЛ – R-CHOP-21 или R-(DA)-EPOCH. Частота ПР у больных HGBL DH и ФЛ составляла 42 и 33% соответственно. Частота прогрессирования заболевания – 50% в обеих группах. Двухлетняя ОВ больных HGBL DH и ФЛ с транслокациями с участием локусов генов c-MYC, BCL2 и/или BCL6 составила 50 и 42% соответственно, p=0,85; 2-летняя БСВ – 33% в обеих группах, p=0,8.
Заключение. Мы продемонстрировали агрессивно протекающий вариант ФЛ 3-го цитологического типа с транслокациями с участием локусов генов c-MYC, BCL2 и/или BCL6, который характеризовался столь же негативным прогнозом, как и HGBL DH.
Ключевые слова: HGBL DH, фолликулярная лимфома, транслокации с участием локусов генов c-MYC, BCL2 и/или BCL6, прогноз заболевания.
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Aim of the issue was to compare clinical characteristics and treatment results of patients with follicular lymphoma (FL) with translocations involving loci of c-MYC/8q24, BCL2/18q21 and/or BCL6/3q27 genes and patients with high-grade B-cell lymphoma [High-grade B-cell lymphoma (HGBL), double-hit (DH)].
Materials and methods. Since 2004 to 2017 years in National Research Center for Hematology 12 patients with high-grade B-cell lymphoma double-hit (HGBL DH) and 6 FL patients with translocations involving c-MYC and BCL2 and/or BCL6 had been treated. We performed a comparative analysis of clinical characterisctics in both groups. As primary endpoints was assessed frequency of complete remission (CR) or progressive disease (PD); as secondary endpoints – overall (OS) and event-free survival (EFS).
Results. 5 patients with HGBL DH had c-MYC/BCL6, 7 – c-MYC/BCL2 rearrangements; 2 patients with FL had c-MYC/BCL2, 3 – c-MYC/BCL6, 1 – c-MYC/BCL2/BCL6 rearrangements. FL was represented by grade 3A in 2, grade 3B – in 4 cases, 3 of them had large-cell transformation. In HGBL DH and FL patients had no significant differences in clinical characteristics. The majority of patients had a widespread tumour, increased LDH activity, high frequency of extranodal and bone marrow involvement. Ki-67 expression level was lower in patients with FL (p<0.05). Patients with HGBL DH were treated with R-BL-M-04, R-(DA)-EPOCH, CHOP–21±R, with FL – R-CHOP-21 or R-(DA)-EPOCH. Frequency of CR in HGBL DH and FL was 42% and 33%, respectively. Frequency of PD was 50% in both groups. Two-year OS of patients with HGBL DH and FL harbouring c-MYC, BCL2 and/or BCL6 rearrangements was 50% and 42% respectively, p=0.85. Two-year EFS was 33% in both groups, p=0.8.
Conclusions. We presented highly aggressive variant of FL grade 3 harbouring c-MYC, BCL2 and/or BCL6 rearrangements that had similarly poor prognosis as patients with HGBL DH.
Keywords: HGBL DH, FL harbouring c-MYC, BCL2 and/or BCL6 rearrangements, prognosis.
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1 ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, Москва, Россия;
2 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Россия;
3 Городская клиническая больница №52, Москва, Россия
________________________________________________
A.E. Misyurina 1, S.K. Kravchenko 1, A.M. Kovrigina 1, A.U. Magomedova 1, L.V. Plastinina1, T.N. Obukhova 1, A.V. Misyurin 2, V.A. Misyurin 2, L.A. Grebenuk 1, F.E. Babaeva1, E.A. Baryakh 3, A.I. Vorobiev 1
1 National Research Center for Hematology, Moscow, Russia;
2 Blokhin National Medical Cancer Research Center, Moscow, Russia;
3 City Clinical Hospital №52, Moscow, Russia