Вовлечение центральной нервной системы и целесообразность профилактики рецидива в центральную нервную систему у больных нодальной формой диффузной В-клеточной крупноклеточной лимфомы (неспецифицированной). Данные проспективного исследования
Вовлечение центральной нервной системы и целесообразность профилактики рецидива в центральную нервную систему у больных нодальной формой диффузной В-клеточной крупноклеточной лимфомы (неспецифицированной). Данные проспективного исследования
Магомедова А.У., Мисюрина А.Е., Мангасарова Я.К. и др. Вовлечение центральной нервной системы и целесообразность профилактики рецидива в центральную нервную систему у больных нодальной формой диффузной В-клеточной крупноклеточной лимфомы (неспецифицированной). Данные проспективного исследования. Терапевтический архив. 2019; 91 (7): 35–40. DOI: 10.26442/00403660.2019.07.000323
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Magomedova A.U., Misyurina A.E., Mangasarova J.K., et al. CNS involvement and the feasibility of intratecal chemotherapy administration in patients with a nodal form of diffuse large B-cell lymphoma not otherwise specified. Data of prospective study. Therapeutic Archive. 2019; 91 (7): 35–40. DOI: 10.26442/00403660.2019.07.000323
Вовлечение центральной нервной системы и целесообразность профилактики рецидива в центральную нервную систему у больных нодальной формой диффузной В-клеточной крупноклеточной лимфомы (неспецифицированной). Данные проспективного исследования
Магомедова А.У., Мисюрина А.Е., Мангасарова Я.К. и др. Вовлечение центральной нервной системы и целесообразность профилактики рецидива в центральную нервную систему у больных нодальной формой диффузной В-клеточной крупноклеточной лимфомы (неспецифицированной). Данные проспективного исследования. Терапевтический архив. 2019; 91 (7): 35–40. DOI: 10.26442/00403660.2019.07.000323
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Magomedova A.U., Misyurina A.E., Mangasarova J.K., et al. CNS involvement and the feasibility of intratecal chemotherapy administration in patients with a nodal form of diffuse large B-cell lymphoma not otherwise specified. Data of prospective study. Therapeutic Archive. 2019; 91 (7): 35–40. DOI: 10.26442/00403660.2019.07.000323
Целью работы является определение показаний к проведению профилактики рецидива диффузной В-клеточной крупноклеточной лимфомы (ДВККЛ) с вовлечением центральной нервной системы (ЦНС) путем введения химиопрепаратов в спинномозговой канал. Материалы и методы. С января 2009 по декабрь 2018 г. в ФГБУ «НМИЦ гематологии» Минздрава России проводилось лечение 102 больным первичной нодальной ДВККЛ старше 18 лет. Всем больным проводили гистологическое и иммуногистохимическое исследования, позволившие исключить трансформацию зрелоклеточной лимфомы в ДВККЛ. Результаты. Вовлечение оболочек головного мозга/нейролейкемия в дебюте заболевания диагностировано у 1 (0,98%) больного. Очагового вовлечения вещества головного мозга не выявлено ни у одного пациента. Более половины больных (54%) имели высокий риск развития рецидива или прогрессии с вовлечением ЦНС: у 8 (7,8%) больных отмечалось вовлечение почек/надпочечников, в таком же проценте – костного мозга, параназальных синусов – у 5 (4,9%), эпидурального пространства – у 7 (6,9%) и молочных желез – у 5 (4,9%) больных. У 82 (80,1%) пациентов определен постгерминальный (из В-клеток постгерминальной дифференцировки – non-GCB) молекулярный подтип ДВККЛ. Заключение. Введение химиопрепаратов в спинномозговой канал показано в единичных случаях, когда в момент манифестации ДВККЛ у больных выявляется вовлечение оболочек/нейролейкемия, и проводится согласно стандартным рекомендациям. Профилактическое введение цитостатических препаратов в спинномозговой канал не показано ввиду отсутствия рецидивов ДВККЛ с вовлечением ЦНС у больных, проходивших лечение как по протоколу m-NHL-BFM-90, так и R-CHOP, R-DA-EPOCH.
Ключевые слова: нодальная диффузная B-клеточная крупноклеточная лимфома, профилактика вовлечения центральной нервной системы в рецидиве заболевания.
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Aim of the issue was to determine indications for intratecal chemotherapy drugs administration to prevent relapse of diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) involvement. Materials and methods. Since January 2009 to December 2018 102 patients with primary nodal DLBCL over 18 years old were treated in the National Research Center for Hematology, Moscow, Russian Federation. Diagnosis were established in all cases according to histological and immunohistochemical studies which made it possible to exclude the transformation of mature B-cell lymphoma into DLBCL. Results. Isolated leptomeningeal involvement of CNS in the debut of the disease was detected in 1 (0.98%) out of 102 patients with DLBCL. Focal brain tissue involvement was not detected in any patient. More than half of the patients (54%) had a high risk of disease recurrence or progression with CNS involvement: in 8 (7.8%) patients had kidney/adrenal involvement, in the same proportion – bone marrow involvement, paranasal sinuses involvement – in 5 (4.9 %), epidural space – in 7 (6.9%) and breast – in 5 (4.9%) of patients. In 82 (80%) patients, a non-GCB (postgerminal differentiation of B-cell analog) molecular subtype of DLBCL was determined. Conclusion. The introduction of chemotherapy drugs into the spinal canal is recommended in isolated cases of leptomeningeal involvement of CNS at the time of DLBCL onset and is carried out according to standard recommendations. Prevention of relapse with involvement of central nervous system using intratecal chemotherapy in patients with nodal form of DLBCL is not indicated due to the absence of cases with disease progression or recurrence into CNS when patients were treated with R-m-NHL-BFM-90, R-DA-EPOCH and R-CHOP protocol.
Keywords: nodal form of diffuse B-cell large cell lymphoma, prophylaxis of relapse with central nervous system involvement.
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1. Kluin PM, Harris NL, Stein H, Leoncini L, Campo E, Jaffe ES, Gaskoyne RD, Swerdlow SN. High-grade B-cell lymphoma. WHO classification of tumours of haematopoietic and lymphoid tissues. 2017:335-341.
2. El-Galaly TC, Cheah CY, Bendtsen MD, Nowakowski GS, Kansara R, Savage KJ, Connors JM, Sehn LH, Goldschmidt N, Shaulov A, Farooq U, Link BK, Ferreri AJM, Calimeri T, Cecchetti C, Dann EJ, Thompson CA, Inbar T, Maurer MJ, Gade IL, Juul MB, Hansen JW, Holmberg S, Larsen TS, Cordua S, Mikhaeel NG, Hutchings M, Seymour JF, Clausen MR, Smith D, Opat S, Gilbertson M, Thanarajasingam G, Villa D. Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma. Eur J Cancer. 2018 Apr;93:57-68. doi: 10.1016/j.ejca.2018.01.073. Epub 2018 Feb 21 [eng.]
3. Holte H, Lepp¨a S, Bj¨orkholm M. Dose-densified hemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013;24(5):1385-92. doi: 10.1093/annonc/mds621 [eng.]
4. Cabannes-Hamy A, Peyrade F, Jardin F, Emile JF, Delwail V, Mounier N, Haioun C, Perrot A, Fitoussi O, Lara D, Delarue R, André M, Offner F, Ghesquières H, Pascal L, Soussain C, Lazarovici J, Schiano JM, Gaulard P, Tilly H, Thieblemont C. LYSA studies. Cancer Medicine. 2018;7(3):539-48. doi: 10.1002/cam4.1139 [eng.]
5. Boehme V, Schmitz N, Zeynalova S, Loeffler M, Pfreundschuh M. CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: an analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Blood. 2009;113(17):3896-902. doi.org/10.1182/blood-2008-10-182253 [eng.]
6. Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 – the Southwest Oncology Group. J Clin Oncol. 2009;27(1):114-9. doi: 10.1200/JCO.2008.16.8021 [eng.]
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8. Villa D, Connors JM, Sehn LH, Gascoyne RD, Savage KJ. Diffuse large B-cell lymphoma with involvement of the kidney: outcome and risk of central nervous system relapse. Haematologica. 2011;96(7):1002-7. doi: 10.3324/haematol.2011.041277 [eng.]
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ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, отделение интенсивной высокодозной химиотерапии с круглосуточным и дневным стационаром (ИВХТ с КС и ДС), Москва, Россия
National Research Center for Hematology, Department of Intensive High-Dose Chemotherapy with Round-the-Clock and Day Hospital (IVHT with CS and DS), Moscow, Russia