bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2019-64-4-447-461bloodjour-165Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВЫСОКОДОЗНАЯ ХИМИОТЕРАПИЯ ПЕРВИЧНОЙ ДИФФУЗНОЙ В-КРУПНОКЛЕТОЧНОЙ ЛИМФОМЫ ЦЕНТРАЛЬНОЙ НЕРВНОЙ СИСТЕМЫ. ПРОМЕЖУТОЧНЫЕ РЕЗУЛЬТАТЫ ПРОТОКОЛА CNS-2015HIGH-DOSE CHEMOTHERAPY FOR PRIMARY DIFFUSE LARGE B-CELL LYMPHOMA OF THE CENTRAL NERVOUS SYSTEM. INTERIM RESULTS OF THE CNS-2015 PROTOCOLhttps://orcid.org/0000-0002-2639-7419ЗвонковЕ. Е.ZvonkovE. E.

Звонков Евгений Евгеньевич, доктор медицинских наук, заведующий отделением интенсивной высокодозной химиотерапии лимфом с  круглосуточным и дневным стационарами 

тел.: +7 (495) 612-44-72; 125167

Evgeny E. Zvonkov*, Dr. Sci. (Med.), Head of the Department of Intensive Highdose Chemotherapy of Lymphomas with a 24-hour Hospital

tel.: +7 (495) 612-44-72

dr.zvonkov@gmail.comhttps://orcid.org/0000-0001-5762-8294КоролеваД. А.KorolevaD. A.

Королева Дарья Александровна, врач-гематолог отделения интенсивной высокодозной химиотерапии лимфом с круглосуточным и дневным стационарами

Daria A. Koroleva, Hematologist, Intensive High-dose Chemotherapy of Lymphomas Department with a 24-hour Hospital

koroleva_12-12@mail.ruhttps://orcid.org/0000-0001-5171-0414ГабееваН. Г.GabeevaN. G.

Габеева Нэлли Георгиевна, кандидат медицинских наук, врачгематолог отделения интенсивной высокодозной химиотерапии лимфом с круглосуточным и дневным стационарами

тел.: +7 (495) 612-4382, доб. 16-97

Nelli G. Gabeeva, Cand. Sci. (Med.), Hematologist, Intensive High-dose Chemotherapy of Lymphomas Department with a 24-hour Hospital

tel.: +7 (495) 612-4382, ext. 16-97

dr.gabeeva@gmail.comГаврилинаО. А.GavrilinaO. A.

Гаврилина Ольга Александровна, кандидат медицинских наук, врач-гематолог отделения интенсивной высокодозной химиотерапии гемобластозов и депрессий кроветворения с круглосуточным стационаром 

ORCID: https//orcid.org/0000-0002-9669-8482

Olga A. Gavrilina, Cand. Sci. (Med.), Hematologist, Intensive High-dose Chemotherapy of Lymphomas Department with a 24-hour Hospital

dr.gavrilina@mail.ruhttps://orcid.org/0000-0002-8239-5442ФедороваС. Ю.FedorovaS. Yu.

Федорова Светлана Юрьевна, врач-невролог лаборатории по изучению психических и неврологических расстройств при заболеваниях системы крови

Svetlana Yu. Fedorova, Neurologist, Laboratory for the Study of Mental and Neurological Disorders in the Setting of Hematologic Diseases

neuro_blood@mail.ruhttps://orcid.org/0000-0003-3698-7751ГубкинА. В.GubkinA. V.

Губкин Андрей Владимирович, кандидат медицинских наук, главный гематолог Центральной дирекции здравоохранения  — филиала ОАО «РЖД», заведующий отделением, врач-гематолог высшей квалификационной категории

Andrey V. Gubkin, Cand. Sci. (Med.), Chief Hematologist, Central Directorate of Healthcare — brunch of JSC “Russian Railways”, Head of Department, boardcertifi ed hematologist (highest category)

gubkinav@gmail.comhttps://orcid.org/0000-0002-1082-8659КовригинаА. М.KovriginaA. M.

Ковригина Алла Михайловна, доктор биологических наук, заведующая патологоанатомическим отделением

Alla M. Kovrigina, Dr. Sci. (Biol.), Head of the Pathology Department

kovrigina.alla@gmail.comhttps://orcid.org/0000-0001-8589-6122ЯцыкГ. А.YatsykG. A.

Яцык Галина Александровна, кандидат медицинских наук, заведующая отделением магнитно-резонансной томографии и ультразвуковой диагностики

Galina A. Yatsyk, Cand. Sci. (Med.), Head of the Department for Magnetic Resonance Imaging and Ultrasound Diagnostics

Yatsyk.g@blood.ruhttps://orcid.org/0000-0001-5973-5763КлясоваГ. А.KlyasovaG. A.

Клясова Галина Александровна, доктор медицинских наук, профессор, заведующая лабораторией клинической бактериологии, микологии и антибиотической терапии

Galina A. Klyasova, Dr. Sci. (Med.), Prof., Head of the Laboratory for Clinical Bacteriology, Mycology and Antibiotic Therapy

klyasova.g@blood.ruhttps://orcid.org/0000-0001-5593-6058СавенкоТ. А.SavenkoT. A.

Савенко Татьяна Александровна, кандидат медицинских наук, заместитель директора по лечебной работе

Tatyana A. Savenko, Cand. Sci. (Med.), Deputy Director for Clinical Care

tan.savenko@gmail.comhttps://orcid.org/0000-0001-8188-5557СавченкоВ. Г.SavchenkoV. G.

Савченко Валерий Григорьевич, доктор медицинских наук, академик РАН, профессор, генеральный директор

Valery G. Savchenko, Dr. Sci. (Med.), RAS Academician, Prof., Head

director@blood.ruФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Research Center for HematologyRussian FederationЦКБ им. Н. А. Семашко ОАО «РЖД»РоссияN.A. Semashko Central Clinical Hospital No. 2, JSC “Russian Railways”Russian Federation201911122019644447–461Copyright © Звонков Е.Е., Королева Д.А., Габеева Н.Г., Гаврилина О.А., Федорова С.Ю., Губкин А.В., Ковригина А.М., Яцык Г.А., Клясова Г.А., Савенко Т.А., Савченко В.Г., 20192019Звонков Е.Е., Королева Д.А., Габеева Н.Г., Гаврилина О.А., Федорова С.Ю., Губкин А.В., Ковригина А.М., Яцык Г.А., Клясова Г.А., Савенко Т.А., Савченко В.Г.Zvonkov E.E., Koroleva D.A., Gabeeva N.G., Gavrilina O.A., Fedorova S.Y., Gubkin A.V., Kovrigina A.M., Yatsyk G.A., Klyasova G.A., Savenko T.A., Savchenko V.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/165Введение

Введение. Основой индукционной химиотерапии (ХТ) первичной диффузной В-крупноклеточной лимфомы центральной нервной системы (ПДВККЛ ЦНС) является применение метотрексата в высоких дозах. Оптимальной стратегией консолидации является высокодозная ХТ с последующей трансплантацией аутологичных гемопоэтических стволовых клеток (ауто-ТГСК). Наиболее эффективным режимом кондиционирования являются комбинации химиопрепаратов с включением тиотепы.

Цель

Цель: предоставить собственный опыт применения ауто-ТГСК/TBC у больных ПДВККЛ ЦНС.

Методы

Методы. С 2015 по 2019 г. в проспективное исследование CNS-2015 было включено 20 больных в возрасте от 20 до 52 лет (медиана 42 года). Соотношение мужчины/женщины = 13/7. Соматический статус у 17 (85 %) больных соответствовал 0–1 баллу по шкале ECOG и только у 3 (15 %) — 4 баллам. Согласно критериям прогностической системы MSKCC, 18 (90 %) больных были отнесены к группе низкого риска и 2 (10 %) больных — к группе среднего риска.

Результаты

Результаты. Всем больным, включенным в исследование, было проведено 3–5 циклов ХТ с метотрексатом в высоких дозах, винкристином, прокарбазином и ритуксимабом (R-MPV) и выполнена ауто-ТГСК с режимом кондиционирования TBC (тиотепа, бусульфан, циклофосфамид). Перед началом ауто-ТГСК у 15 их 20 больных, у которых полностью завершили индукционную ХТ, была достигнута полная ремиссия, а у 5 — частичная ремиссия. У 5 больных с исходным частичным ответом после ауто-ТГСК удалось достичь полной ремиссии. Всем больным проводилась поддерживающая терапия темозоломидом в течение 2 лет. При медиане наблюдения 17 (1–46) месяцев 18 больных живы и находятся в ремиссии заболевания. Двое больных, у которых развился рецидив заболевания (+4 и +5 месяцы после ауто-ТГСК) и не было ответа на вторую линию ХТ и лучевую терапию, умерли через 24 и 26 месяцев после ауто-ТГСК.

Заключение

Заключение. Режим R-MPV является эффективным методом лечения больных ПДВККЛ ЦНС, не сопровождающийся тяжелой токсичностью. Применение высокодозной ХТ по программе TBC позволяет достичь высокой частоты ремиссий, при этом смертность, связанная с лечением, в группе больных, включенных в протокол, была равна 0 %.

Introduction

Introduction. Induction chemotherapy (CT) for primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is based on the use of methotrexate in high doses. An optimal consolidation strategy involves high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation (auto-HSCT). The most effective conditioning regimen comprises a combination of chemotherapy agents including thiotepa.

Aim

Aim. To present the authors’ experience of applying auto-HSCT/TBC in patients with primary DLBCL of the CNS.

Methods

Methods. The prospective study CNS-2015 was carried out among 20 patients aged 20–52 years (median 42 years old) from 2015 to 2019. The male/female ratio came to 13/7. The somatic status of 17 (85 %) patients was 0–1 on the ECOG scale. Only 3 (15 %) patients showed the somatic status of 4 points. According to the criteria of the MSKCC prognostic system, 18 (90 %) and 2 (10 %) patients were assigned to the low-risk and medium-risk groups, respectively.

Results

Results. All patients included in the study received 3–5 cycles of chemotherapy with high doses of methotrexate, vincristine, procarbazine and rituximab (R-MPV), as well as underwent auto-HSCT following TBC-based conditioning regimen (thiotepa, busulfan, cyclophosphamide). Prior to auto-HSCT, 15 and 5 out of 20 patients having completed induction chemotherapy achieved complete remission and partial remission, respectively. Following auto-HSCT, complete remission was achieved in 5 patients with an initial partial response to treatment. All patients underwent temozolomide maintenance therapy for 2 years. With a median follow-up of 17 (1–46) months, 18 patients are alive and in remission. Two patients, who relapsed 4 and 5 months after auto-HSCT and achieved no response to the second line of chemotherapy and radiation therapy, died 24 and 26 months after auto-HSCT.

Conclusion

Conclusion. R-MPV is an effective treatment for patients with primary DLBCL of CNS, which is not accompanied by severe toxicity. The use of high-dose chemotherapy with TBC allows a high remission rate to be achieved. The mortality associated with treatment in the group of patients included in the study came to 0 %.

первичная диффузная В-крупноклеточная лимфома центральной нервной системытрансплантация аутологичных гемопоэтических стволовых клеток кровивысокодозная химиотерапияprimary DLBCLCNSauto-HSCThigh-dose chemotherapyРабота выполнена при поддержке Министерства здравоохранения РФ (Клиническая апробация «Метод улучшения эффективности программной химиотерапии первичной диффузной В-крупноклеточной лимфомы ЦНС»). Благодарность. Авторы выражают благодарность коллективу ФГАУ «НМИЦ нейрохирургии им. академика Н.Н. Бурденко» за оказанную помощь в проведении исследования.This study was supported by the Ministry of Health of the Russian Federation (Clinical testing “Method for Improving the Efficacy of the Chemotherapy Regimen for Primary Diffuse Large B-cell Lymphoma of the Central Nervous System”) Acknowledgments. The authors express their gratitude to the staff of the N. N. 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The authors declare that there are no conflicts of interest present.