bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2020-65-4-386-402bloodjour-242Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESТрансплантация аллогенных гемопоэтических стволовых клеток с применением режимов кондиционирования со сниженной интенсивностью доз у больных хроническим миелолейкозомAllogeneic haematopoietic stem cell transplantation with reduced-intensity conditioning in chronic myeloid leukaemiahttps://orcid.org/0000-0002-0125-864XМорозоваЕ. В.MorozovaE. V.

Морозова Елена Васильевна, кандидат медицинских наук, заведующая кафедрой онкологии, гематологии и трансплантологии для подростков и взрослых НИИ детской онкологии, гематологии и трансплантологии им. Р.М.Горбачевой; доцент кафедры гематологии, трансфузиологии и трансплантологии ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. академика И. П. Павлова» Министерства здравоохранения Российской Федерации

Elena V. Morozova, Cand. Sci. (Med.), Head of the Department of Oncology, Hematology and Transplantology for Adolescents and Adults, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint-Petersburg State Medical University; Associate Professor, Chair of Hematology, Transfusiology and Transplantation, Pavlov First Saint-Petersburg State Medical University

197022, St. Petersburg

dr_morozova@mail.ruhttps://orcid.org/0000-0002-7762-0107ВласоваЮ. Ю.VlasovaY. I.

Власова Юлия Юрьевна, кандидат медицинских наук, заведующая приемным отделением № 3, врач-гематолог

Yulia Yu. Vlasova, Cand. Sci. (Med.), Head of the Admission Unit No. 3; Haematologist

197022, St. Petersburg

jj_vlasova@mail.ruhttps://orcid.org/0000-0002-5273-5581БарабанщиковаМ. В.BarabanshikovaM. V.

Барабанщикова Мария Владимировна, кандидат медицинских наук, старший научный сотрудник отдела детской онкологии, гематологии и трансплантологии

Maria V. Barabanshikova, Cand. Sci. (Med.), Senior Researcher, Department of Oncology, Hematology and Transplantology for Children

197022, St. Petersburg

maria.barabanshikova.spb@gmail.comhttps://orcid.org/0000-0002-2953-4300АфанасьеваК. С.AfanasevaK. S.

Афанасьева Ксения Сергеевна, клинический ординатор кафедры гематологии, трансфузиологии и трансплантологии

Ksenia S. Afanaseva, Clinical Resident, Chair of Hematology, Transfusiology and Transplantation

197022, St. Petersburg

afanasevaksenya11@gmail.comhttps://orcid.org/0000-0002-9032-6885ЮровскаяК. С.IurovskaiaK. S.

Юровская Ксения Сергеевна, врач-гематолог

Ksenia S. Iurovskaia, Hematologist, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation

197022, St. Petersburg

Ksenia_Kud_@mail.ruhttps://orcid.org/0000-0002-1302-3311ГиндинаТ. Л.GindinaT. L.

Гиндина Татьяна Леонидовна, кандидат медицинских наук, заведующая лабораторией цитогенетики и диагностики генетических заболеваний

Tatyana L. Gindina, Cand. Sci. (Med.), Head of the Laboratory of Cytogenetics and Genetic Disease Diagnostics

197022, St. Petersburg

tatgindina@gmail.comhttps://orcid.org/0000-0002-8000-3652БархатовИ. М.BarchatovI. M.

Бархатов Ильдар Мунерович, кандидат медицинских наук, заведующий лабораторией молекулярной гематологии и трансплантологии

Ildar M. Barchatov, Cand. Sci. (Med.), Head of the Laboratory of Molecular Hematology and Transplantation

197022, St. Petersburg

i.barkhatov@inbox.ruhttps://orcid.org/0000-0003-3910-6972АлянскийА. Л.AlyanskiyA. L.

Алянский Александр Леонидович, заведующий лабораторией Регистр доноров костного мозга

Alexandr L. Alyanskiy, Head of the Bone Marrow Donor Registry

197022, St. Petersburg

aalyanskiy@gmail.comhttps://orcid.org/0000-0002-5694-4348БакинЕ. А.BakinE. A.

Бакин Евгений Александрович, кандидат технических наук, старший научный сотрудник

Evgenii A. Bakin, Cand. Senior Researcher

197022, St. Petersburg

eugene.bakin@gmail.comhttps://orcid.org/0000-0002-2446-8092БондаренкоС. Н.BondarenkoS. N.

Бондаренко Сергей Николаевич, кандидат медицинских наук, заместитель директора по клинике

Sergei N. Bondarenko, Cand. Sci. (Med.), Deputy Director for Clinic

197022, St. Petersburg

dr.sergeybondarenko@gmail.comhttps://orcid.org/0000-0002-4332-0114МоисеевИ. С.MoiseevI. S.

Моисеев Иван Сергеевич, кандидат медицинских наук, заместитель директора по науке

Ivan S. Moiseev, Cand. Sci. (Med.), Deputy Director for Science

197022, St. Petersburg

moisiv@mail.ruhttps://orcid.org/0000-0003-2594-7703ЗубаровскаяЛ. С.ZubarovskayaL. S.

Зубаровская Людмила Степановна, доктор медицинских наук, профессор кафедры гематологии, трансфузиологии, трансплантологии, ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. академика И. П. Павлова» Министерства здравоохранения Российской Федерации; руководитель отдела детской онкологии, гематологии и трансплантологии, НИИ детской онкологии, гематологии и трансплантологии им. Р. М. Горбачевой

Ludmila S. Zubarovskaya, Dr. Sci. (Med.), Professor, Chair of Hematology, Transfusiology and Transplantation, Pavlov First Saint-Petersburg State Medical University; Head of the Department of Oncology, Hematology and Transplantation for Children, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation

197022, St. Petersburg

zubarovskaya_ls@mail.ruhttps://orcid.org/0000-0002-1235-4530АфанасьевБ. В.AfanasyevB. V.

Афанасьев Борис Владимирович, доктор медицинских наук, профессор, директор

Boris V. Afanasyev, Dr. Sci. (Med.), Professor, Director

197022, St. Petersburg

bmt-director@spb-gmu.ruНИИ детской онкологии, гематологии и трансплантологии им. Р. М. Горбачевой; ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. академика И. П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияRaisa Gorbacheva Memorial Research Institute for Pediatric Oncology; Hematology and Transplantation of the Pavlov First Saint Petersburg State Medical UniversityRussian Federation202009122020654386402Copyright © Морозова Е.В., Власова Ю.Ю., Барабанщикова М.В., Афанасьева К.С., Юровская К.С., Гиндина Т.Л., Бархатов И.М., Алянский А.Л., Бакин Е.А., Бондаренко С.Н., Моисеев И.С., Зубаровская Л.С., Афанасьев Б.В., 20202020Морозова Е.В., Власова Ю.Ю., Барабанщикова М.В., Афанасьева К.С., Юровская К.С., Гиндина Т.Л., Бархатов И.М., Алянский А.Л., Бакин Е.А., Бондаренко С.Н., Моисеев И.С., Зубаровская Л.С., Афанасьев Б.В.Morozova E.V., Vlasova Y.I., Barabanshikova M.V., Afanaseva K.S., Iurovskaia K.S., Gindina T.L., Barchatov I.M., Alyanskiy A.L., Bakin E.A., Bondarenko S.N., Moiseev I.S., Zubarovskaya L.S., Afanasyev B.V.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/242Введение

Введение. Трансплантация аллогенных гемопоэтических стволовых клеток (алло-ТГСК) является единственным методом, позволяющим добиться излечения больных хроническим миелолейкозом (ХМЛ).

Цель исследования

Цель исследования: анализ результатов алло-ТГСК с применением режимов кондиционирования со сниженной интенсивностью доз (РИК) у больных ХМЛ.

Материалы и методы

Материалы и методы. В ретроспективное исследование включено 110 больных ХМЛ, которым была выполнена аллоТГСК с 1995 по 2019 гг. РИК включал бусульфан в дозе 8–12 мг/кг, флударабин 180 мг/м2 или мелфалан 140 мг/м2, флударабин 180 мг/м2. Медиана времени начала терапии ингибиторами тирозинкиназ (ИТК) составила 60 дней после алло-ТГСК (30–835). Профилактику реакции «трансплантат против хозяина» (РТПХ) в посттрансплантационном периоде циклофосфамидом в высоких дозах (ПТЦф) 50 мг/кг на 3–4-й дни после алло-ТГСК (Д+3, Д+4) получали 61 % (n = 67) больных, антитимоцитарный глобулин (АТГАМ) 60 мг/кг — 17 % (n = 19) больных, тимоглобулин 5 мг/кг — 3 % (n = 3). Результаты. В исследуемой группе 50 % (n = 55) больных относились ко второй и последующим хроническим фазам (ХФ ≥ 2), 25 % (n = 27) — к фазе акселерации (ФА), 9 % (n = 10) — к фазе бластного криза (БК). Среди больных в ХФ ≥ 2 у 63 % (n = 58) отмечался БК в анамнезе, у 25 % (n = 23) — 2 и более БК. Однолетняя летальность, не связанная с рецидивом (ЛНР), составила 21 % (95 % доверительный интервал (ДИ) 15–31 %). Применение ПТЦф в качестве профилактики РТПХ по сравнению с другими режимами значительно снижало риск однолетней ЛНР: 11 % (95 % ДИ 5–20 %) против 38 % (95 % ДИ 23–53 %) (р = 0,001). Частота острой РТПХ II–IV степени составила 23 % (95 % ДИ 15–31 %), хроническая РТПХ средней и тяжелой степени — 15 % (95 % ДИ 9–22 %). В 49 % (n = 29) случаев ИТК назначались с целью профилактики рецидива, в 40 % (n = 24) — в связи с отсутствием ответа после алло-ТГСК, в 10 % (n = 6) — в связи с рецидивом. Инфузии донорских лимфоцитов (ИДЛ) получили 37 больных, основными показаниями к ИДЛ были BCR-ABL-позитивный статус — 24 % (n = 9) и рецидив — 49 % (n = 18). Трехлетняя частота рецидива составила 36 % (95 % ДИ 26–46 %), 5-летняя безрецидивная выживаемость (БРВ) составила 40 % (95 % ДИ 29–51 %). Трансплантация в ФА или БК достоверно увеличивала частоту рецидива — отношение рисков 2,4800 (1,2180–5,050), р = 0,012. Пятилетняя общая выживаемость составила 52 % (95 % ДИ 40–62 %), отсутствие БК в анамнезе и ПТЦф было ассоциировано с более высокой 5-летней общей выживаемостью (отношение рисков 1,9990 (1,0700–3,7350), р = 0,029 и 0,3126 (0,1670–0,5851), р = 0,0002 соответственно).

Заключение

Заключение. Применение РИК имеет преимущества у больных ХМЛ с длительным анамнезом заболевания, у которых было нескольких линий терапии ИТК. Уменьшение осложнений в посттрансплантационном периоде связано с применением ПТЦф. Однако рецидивы заболевания остаются проблемой при выполнении алло-ТГСК с РИК. Применение ИТК и ИДЛ в посттрансплантационном периоде позволяет достигнуть ответа у 54 % больных. Результаты алло-ТГСК во многом зависят от статуса заболевания на момент выполнения трансплантации (ХФ, ФА, БК).

Introduction

Introduction. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for chronic myeloid leukaemia (CML).

Aim

Aim. Analysis of allo-HSCT outcomes in CML patients following reduced-intensity conditioning (RIC) regimens.

Materials and methods

Materials and methods. This retrospective study included 110 CML patients who underwent allo-HSCT in 1995–2019. RIC regimens included busulfan (8–12 mg/kg), fludarabine (180 mg/m2) or melphalan (140 mg/m2), fludarabine (180 mg/m2). The median onset time for treatment with tyrosine kinase inhibitors (TKIs) was 60 days after allo-HSCT (30–835). Post-transplant graft-versus-host-disease (GVHD) prevention with cyclophosphamide (Cy) at high doses (PTCy) of 50 mg/kg in 3–4 days after allo-HSCT (D+3, D+4) was ordered in 61 % (n = 67), with antithymocyte globulin (ATGAM) 60 mg/kg — in 17 % (n = 19), with thymoglobulin 5 mg/kg — in 3 % (n = 3) of the patients.

Results

Results. In the study cohort, 50 % (n = 55) of the patients had chronic phase 2 and higher (CP ≥ 2), 25 % (n = 27) — accelerated phase (AP), 9 % (n = 10) — blast crisis (BC) phase of the disease. Among CP ≥ 2 patients, 63 % (n = 58) had a BC in history, and 25 % (n = 23) — 2 or more BCs. One-year non-relapse mortality (NRM) was 21 % (95 % CI 15–31). PTCy prevention of GVHD significantly reduced the NRM risk relative to other schemes: 11 % (95 % CI 5–20) vs. 38 % (95 % CI 23–53) (p = 0.001). Acute GVHD II–IV had a rate of 23 % (95 % CI 15–31), chronic GVHD of moderate to severe degree 15 % (95 % CI 9–22). TKIs were used in 49 % (n = 29) cases for relapse prevention, in 40 % (n = 24) — due to the lack of response to allo-HSCT, in 10 % (n = 6) — in relapse. Donor lymphocyte infusion (DLI) was performed in 37 patients mainly in BCR-ABL positive cases (24 %, n = 9) and relapse (49 %, n = 18). Three-year relapse rate was 36 % (95 % CI 26–46), and five-year relapse-free survival (RFS) was 40 % (95 % CI 29–51). Transplantation in AP or BC phase significantly increased the relapse rate (odds ratio 2.4800 (1.2180–5.050), p = 0.012). Five-year overall survival was 52 % (95 % CI 40–62), a clean BC history and PTCy correlated with a higher 5-year overall survival (odds ratios 1.9990 (1.0700–3.7350), p = 0.029, and 0.3126 (0.1670–0.5851), p = 0.0002, respectively).

Conclusion

Conclusion. Reduced-intensity conditioning is advantageous in patients with long-term CML and several lines of TKI therapy in history. Post-transplant complication relief is associated with PTCy prevention. Relapse instances, however, complicate the outcomes of allo-HSCT with RIC. Post-transplant TKI and DLI facilitate response in 54 % of the patients. Success of allo-HSCT largely depends on the disease phase (CP, AP, BC) at the time of transplantation.

трансплантация аллогенных гемопоэтических стволовых клетокхронический миелолейкозрежимы кондиционированияallo-HSCTchronic myeloid leukaemiaconditioning regimensReferencesАфанасьев Б.В. Результаты различных видов аллогенных трансплантаций гемопоэтических стволовых клеток у детей и взрослых. Клеточная трансплантология и тканевая инженерия. 2011; 6(1): 11.Afanasyev B. The results of various types of allogeneic hematopoietic stem cell transplantation in children and adults. Cell transplantation and tissue engineering. Kletochnaya transplantologiya i tkanevaya inzheneriya. 2011; 6(1): 11 (In Russian).Bacher U., Klyuchnikov E., Zabelina T. et al. The changing scene of allogeneic stem cell transplantation for chronic myeloid leukemia — A report from the German Registry covering the period from 1998 to 2004. Ann Hematol. 2009; 88(12): 1237–47. DOI: 10.1007/s00277-009-0737-3.Bacher U., Klyuchnikov E., Zabelina T. et al. The changing scene of allogeneic stem cell transplantation for chronic myeloid leukemia — A report from the German Registry covering the period from 1998 to 2004. Ann Hematol. 2009; 88(12): 1237–47. DOI: 10.1007/s00277-009-0737-3.Radujkovic A., Guglielmi C., Bergantini S. et al. Donor lymphocyte infusions for chronic myeloid leukemia relapsing after allogeneic stem cell transplantation: May we predict Graft-versus-Leukemia without Graft-versus-Host disease? Biol Blood Marrow Transplant. 2015; 21(7): 1230–6. DOI: 10.1016/j.bbmt.2015.03.012.Radujkovic A., Guglielmi C., Bergantini S. et al. Donor lymphocyte infusions for chronic myeloid leukemia relapsing after allogeneic stem cell transplantation: May we predict Graft-versus-Leukemia without Graft-versus-Host disease? Biol Blood Marrow Transplant. 2015; 21(7): 1230–6. DOI: 10.1016/j.bbmt.2015.03.012.Radich J.P., Gooley T., Bensinger W. et al. HLA-matched related hematopoietic cell transplantation for chronic-phase CML using a targeted busulfan and cyclophosphamide preparative regimen. Blood. 2003; 102(1): 31–5. DOI: 10.1182/blood-2002-08-2619.Radich J.P., Gooley T., Bensinger W. et al. HLA-matched related hematopoietic cell transplantation for chronic-phase CML using a targeted busulfan and cyclophosphamide preparative regimen. Blood. 2003; 102(1): 31–5. DOI: 10.1182/blood-2002-08-2619.Socié G., Clift R.A., Biaise D. et al. Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: Long-term follow-up of 4 randomized studies. Blood. 2001; 98(13): 3569–74. DOI: 10.1182/blood.V98.13.3569.Socié G., Clift R.A., Biaise D. et al. Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: Long-term follow-up of 4 randomized studies. Blood. 2001; 98(13): 3569–74. DOI: 10.1182/blood.V98.13.3569.Khoury H.J., Kukreja M., Goldman J.M. et al. Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: A CIBMTR analysis. Bone Marrow Transplant. 2012; 47(6): 810–6. DOI: 10.1038/bmt.2011.194.Khoury H.J., Kukreja M., Goldman J.M. et al. Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: A CIBMTR analysis. Bone Marrow Transplant. 2012; 47(6): 810–6. DOI: 10.1038/bmt.2011.194.Gratwohl A., Brand R., Apperley J. et al. Graft-versus-host disease and outcome in HLA-identical sibling transplantations for chronic myeloid leukemia. Blood. 2002; 100(12): 3877–86. DOI: 10.1182/blood.V100.12.3877.Gratwohl A., Brand R., Apperley J. et al. Graft-versus-host disease and outcome in HLA-identical sibling transplantations for chronic myeloid leukemia. Blood. 2002; 100(12): 3877–86. DOI: 10.1182/blood.V100.12.3877.Stern M., de Wreede L.C., Brand R. et al. Impact of Graft-versus-Host disease on relapse after allogeneic hematopoietic stem cell transplantation, an EBMT Megafile study. Blood. 2012; 120(21): 469. DOI: 10.1182/blood.v120.21.469.469.Stern M., de Wreede L.C., Brand R. et al. Impact of Graft-versus-Host disease on relapse after allogeneic hematopoietic stem cell transplantation, an EBMT Megafile study. Blood. 2012; 120(21): 469. DOI: 10.1182/blood.v120.21.469.469.Champlin R., Khouri I., Anderlini P. et al. Nonmyeloablative preparative regimens for allogeneic hematopoietic transplantation. Bone Marrow Transplant. 2001; 27(S2): S13–22. DOI: 10.1038/sj.bmt.1702864.Champlin R., Khouri I., Anderlini P. et al. Nonmyeloablative preparative regimens for allogeneic hematopoietic transplantation. Bone Marrow Transplant. 2001; 27(S2): S13–22. DOI: 10.1038/sj.bmt.1702864.Kolb H.-J. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008; 112(12): 4371–83. DOI: 10.1182/blood-2008-03-077974.Kolb H.-J. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008; 112(12): 4371–83. DOI: 10.1182/blood-2008-03-077974.Зубаровская Л.С., Фрегатова Л.М., Афанасьев Б.В. Трансплантация гемопоэтических стволовых клеток при гемобластозах. Клиническая онкогематология, под ред. М.А. Волковой. М.: Медицина, 2001. С. 479–94.Zubarovskaya L.S., Fregatova L.M., Afanasyev B.V. Haematopoietic stem cell transplantation in haemoblastoses. Clinical Oncohematology, Ed. M.A. Volkova, Moscow: Medicine, 2001. P. 479–94 (In Russian).Gratwohl A. The EBMT risk score. Bone Marrow Transplant. 2012; 47: 749–56. DOI: 10.1038/bmt.2011.110.Gratwohl A. The EBMT risk score. Bone Marrow Transplant. 2012; 47: 749–56. DOI: 10.1038/bmt.2011.110.Любимова Л.С., Кузьмина Л.А., Урнова Е.С. и др. HLA-идентичная трансплантация костного мозга в первой хронической фазе хронического миелолейкоза в ранние сроки заболевания или длительная терапия ингибиторами тирозинкиназ? Гематология и трансфузиология. 2012; 57(3): 6–10.Lyubimova L.S., Kuzmina L.A., Urnova E.S. et al. HLA-identical bone marrow transplantation in chronic phase 1 of chronic myeloid leukaemia early in disease or a long-term therapy with tyrosine kinase inhibitors? Gematologiya i transfuziologiya. 2012; 57(3): 6–10 (In Russian).Slavin S., Nagler A., Naparstek E. et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998; 91(3): 756–63.Slavin S., Nagler A., Naparstek E. et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998; 91(3): 756–63.Chhabra S., Ahn K.W., Hu Z.H. et al. Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia. Blood Adv. 2018; 2(21): 2922–36. DOI: 10.1182/bloodadvances.2018024844.Chhabra S., Ahn K.W., Hu Z.H. et al. Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia. Blood Adv. 2018; 2(21): 2922–36. DOI: 10.1182/bloodadvances.2018024844.Lübking A., Dreimane A., Sandin F. et al. Allogeneic stem cell transplantation for chronic myeloid leukemia in the TKI era: population-based data from the Swedish CML registry. Bone Marrow Transplant. 2019; 54(11): 1764–74. DOI: 10.1038/s41409-019-0513-5.Lübking A., Dreimane A., Sandin F. et al. Allogeneic stem cell transplantation for chronic myeloid leukemia in the TKI era: population-based data from the Swedish CML registry. Bone Marrow Transplant. 2019; 54(11): 1764–74. DOI: 10.1038/s41409-019-0513-5.Radujkovic A., Dietrich S., Blok H.-J. et al. Allogeneic stem cell transplantation for blast crisis chronic myeloid leukemia in the era of tyrosine kinase inhibitors: A retrospective study by the EBMT Chronic Malignancies Working Party. Biol Blood Marrow Transplant. 2019; 25(10): 2008–16. DOI: 10.1016/J.BBMT.2019.06.028.Radujkovic A., Dietrich S., Blok H.-J. et al. Allogeneic stem cell transplantation for blast crisis chronic myeloid leukemia in the era of tyrosine kinase inhibitors: A retrospective study by the EBMT Chronic Malignancies Working Party. Biol Blood Marrow Transplant. 2019; 25(10): 2008–16. DOI: 10.1016/J.BBMT.2019.06.028.Champlin R., de Lima M., Kebriaei P. et al. Nonmyeloablative allogeneic stem cell transplantation for chronic myelogenous leukemia in the imatinib era. Clin Lymphoma Myeloma; 2009; 9(Suppl 3): S261–5. DOI: 10.3816/clm.2009.s.021.Champlin R., de Lima M., Kebriaei P. et al. Nonmyeloablative allogeneic stem cell transplantation for chronic myelogenous leukemia in the imatinib era. Clin Lymphoma Myeloma; 2009; 9(Suppl 3): S261–5. DOI: 10.3816/clm.2009.s.021.Kebriaei P., Detry M.A., Giralt S. et al. Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia. Blood. 2007; 110(9): 3456–62. DOI: 10.1182/blood-2007-04-085969.Kebriaei P., Detry M.A., Giralt S. et al. Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia. Blood. 2007; 110(9): 3456–62. DOI: 10.1182/blood-2007-04-085969.Weisser M., Schleuning M., Ledderose G. et al. Reduced-intensity conditioning using TBI (8 Gy), fludarabine, cyclophosphamide and ATG in elderly CML patients provides excellent results especially when performed in the early course of the disease. Bone Marrow Transplant. 2004; 34(12): 1083–8. DOI: 10.1038/sj.bmt.1704664.Weisser M., Schleuning M., Ledderose G. et al. Reduced-intensity conditioning using TBI (8 Gy), fludarabine, cyclophosphamide and ATG in elderly CML patients provides excellent results especially when performed in the early course of the disease. Bone Marrow Transplant. 2004; 34(12): 1083–8. DOI: 10.1038/sj.bmt.1704664.Туркина А.Г., Зарицкий А.Ю., Челышева Е.Ю. и др. Клинические рекомендации по диагностике и лечению хронического миелолейкоза. Клиническая онкогематология. 2017; 10(3): 294–316. DOI: 10.21320/25002139-2017-10-3-294-316.Turkina A.G., Zaritsky A.Yu., Chelysheva E.Yu. et al. Clinical recommendations on diagnosis and treatment of chronic myelogenous leukaemia. Klinicheskaya oncogematologiya. 2017; 10(3): 294–316. DOI: 10.21320/2500-2139-2017-103-294-316. (In Russian).Baccarani M., Deininger M.W., Rosti G. et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013; 122: 872–84. DOI: 10.1182/blood-2013-05-501569.Baccarani M., Deininger M.W., Rosti G. et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013; 122: 872–84. DOI: 10.1182/blood-2013-05-501569.Kröger N., Holler E., Kobbe G. et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: A prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood. 2009; 114(26): 5264–70. DOI: 10.1182/blood-2009-07-234880.Kröger N., Holler E., Kobbe G. et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: A prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood. 2009; 114(26): 5264–70. DOI: 10.1182/blood-2009-07-234880.Radich J.P., Deininger M., Abboud C.N. et al. Chronic myeloid leukemia, version 1.2019. NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018; 16(9): 1108–35. DOI: 10.6004/jnccn.2018.0071.Radich J.P., Deininger M., Abboud C.N. et al. Chronic myeloid leukemia, version 1.2019. NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018; 16(9): 1108–35. DOI: 10.6004/jnccn.2018.0071.Sorror M.L., Maris M.B., Storb R. et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: A new tool for risk assessment before allogeneic HCT. Blood. 2005; 106(8): 2912–9. DOI: 10.1182/blood-2005-05-2004.Sorror M.L., Maris M.B., Storb R. et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: A new tool for risk assessment before allogeneic HCT. Blood. 2005; 106(8): 2912–9. DOI: 10.1182/blood-2005-05-2004.Oken M.M., Creech R.H., Tormey D.C. et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 5(6): 649–55.Oken M.M., Creech R.H., Tormey D.C. et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 5(6): 649–55.Porkka K., Koskenvesa P., Lundán T. et al. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system philadelphia chromosome positive leukemia. Blood. 2008; 112(4): 1005–12. DOI: 10.1182/blood-2008-02-140665.Porkka K., Koskenvesa P., Lundán T. et al. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system philadelphia chromosome positive leukemia. Blood. 2008; 112(4): 1005–12. DOI: 10.1182/blood-2008-02-140665.Rowlings P.A., Przepiorka D., Klein J.P. et al. IBMTR Severity index for grading acute graft versus host disease: retrospective comparison with Glucksberg GRADE. Br J Haematol. 1997; 97(4): 855–64. DOI: 10.1046/j.1365-2141.1997.1112925.x.Rowlings P.A., Przepiorka D., Klein J.P. et al. IBMTR Severity index for grading acute graft versus host disease: retrospective comparison with Glucksberg GRADE. Br J Haematol. 1997; 97(4): 855–64. DOI: 10.1046/j.1365-2141.1997.1112925.x.Jagasia M.H., Greinix H.T., Arora M. et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report. Biol Blood Marrow Transplant. 2015; 21(3): 389–401.e1. DOI: 10.1016/j.bbmt.2014.12.001.Jagasia M.H., Greinix H.T., Arora M. et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report. Biol Blood Marrow Transplant. 2015; 21(3): 389–401.e1. DOI: 10.1016/j.bbmt.2014.12.001.McDonald G.B., Hinds M.S., Fisher L.D. et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: A cohort study of 355 patients. Ann Intern Med. 1993; 118(4): 255–67. DOI: 10.7326/00034819-118-4-199302150-00003.McDonald G.B., Hinds M.S., Fisher L.D. et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: A cohort study of 355 patients. Ann Intern Med. 1993; 118(4): 255–67. DOI: 10.7326/00034819-118-4-199302150-00003.Pauwa B. De, Walsh T.J., Donnelly J.P. Stevens D.A., Edwards J.E., Calandra T. et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008; 8(5): 1813–21. DOI: 10.1086/588660.Pauwa B. De, Walsh T.J., Donnelly J.P. Stevens D.A., Edwards J.E., Calandra T. et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008; 8(5): 1813–21. DOI: 10.1086/588660.Moiseev I.S., Pirogova O.V., Alyanski A.L. et al. Graft-versus-Host disease prophylaxis in unrelated peripheral blood stem cell transplantation with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Biol Blood Marrow Transplant. 2016; 22(6): 1037–42. DOI: 10.1016/j.bbmt.2016.03.004.Moiseev I.S., Pirogova O.V., Alyanski A.L. et al. Graft-versus-Host disease prophylaxis in unrelated peripheral blood stem cell transplantation with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Biol Blood Marrow Transplant. 2016; 22(6): 1037–42. DOI: 10.1016/j.bbmt.2016.03.004.Nicolini F., Modolo L., Raus N. et al. Allogeneic stem cell transplantation for blast crisis (BC) chronic myelogenous leukemia (CML) in the tyrosine kinase inhibitors (TKIs) era. Analysis of pre-transplant variables on transplant outcome. On behalf of the Societe Française De Greffe De Moelle et De Therapie Cellulaire and the French Group of CML. Blood. 2010; 116(21): 2266. DOI: 10.1182/blood.V116.21.2266.2266.Nicolini F., Modolo L., Raus N. et al. Allogeneic stem cell transplantation for blast crisis (BC) chronic myelogenous leukemia (CML) in the tyrosine kinase inhibitors (TKIs) era. Analysis of pre-transplant variables on transplant outcome. On behalf of the Societe Française De Greffe De Moelle et De Therapie Cellulaire and the French Group of CML. Blood. 2010; 116(21): 2266. DOI: 10.1182/blood.V116.21.2266.2266.Mohty M., Labopin M., Volin L. et al. Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: A retrospective study from the European Group for Blood and Marrow Transplantation. Blood. 2010; 116(22): 4439–43. DOI: 10.1182/blood-2010-02-266551.Mohty M., Labopin M., Volin L. et al. Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: A retrospective study from the European Group for Blood and Marrow Transplantation. Blood. 2010; 116(22): 4439–43. DOI: 10.1182/blood-2010-02-266551.Nykolyszyn C., Granata A., Pagliardini T. et al. Posttransplantation cyclophosphamide vs. antithymocyte globulin as GVHD prophylaxis for mismatched unrelated hematopoietic stem cell transplantation. Bone Marrow Transplant. 2020; 55(2): 349–55. DOI: 10.1038/s41409-019-0682-2.Nykolyszyn C., Granata A., Pagliardini T. et al. Posttransplantation cyclophosphamide vs. antithymocyte globulin as GVHD prophylaxis for mismatched unrelated hematopoietic stem cell transplantation. Bone Marrow Transplant. 2020; 55(2): 349–55. DOI: 10.1038/s41409-019-0682-2.Morozova E.V., Moiseev I.S., Vlasova Y.Y. et al. Randomized study between thymoglobulin and posttransplant cyclophosphamide in patients with chronic myeloid neoplasms undergoing unrelated allogeneic stem cell transplantation. Cell Ther Transplant. 2020; 9(1): 53–9. DOI: 10.18620/ctt-1866-8836-2020-9-1-53-59.Morozova E.V., Moiseev I.S., Vlasova Y.Y. et al. Randomized study between thymoglobulin and posttransplant cyclophosphamide in patients with chronic myeloid neoplasms undergoing unrelated allogeneic stem cell transplantation. Cell Ther Transplant. 2020; 9(1): 53–9. DOI: 10.18620/ctt-1866-8836-2020-9-1-53-59.DeFilipp Z., Ancheta R., Liu Y. et al. Maintenance tyrosine kinase inhibitors following allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia: A Center for International Blood and Marrow Transplant Research study. Biol Blood Marrow Transplant. 2020; 26(3): 472–9. DOI: 10.1016/j.bbmt.2019.10.017.DeFilipp Z., Ancheta R., Liu Y. et al. Maintenance tyrosine kinase inhibitors following allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia: A Center for International Blood and Marrow Transplant Research study. Biol Blood Marrow Transplant. 2020; 26(3): 472–9. DOI: 10.1016/j.bbmt.2019.10.017.Kolb H.J., Mittermuller J., Clemm C. et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 1990; 76(12): 2462–5. DOI: 10.1182/blood.v76.12.2462.bloodjournal76122462.Kolb H.J., Mittermuller J., Clemm C. et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 1990; 76(12): 2462–5. DOI: 10.1182/blood.v76.12.2462.bloodjournal76122462.Chalandon Y., Passweg J.R., Guglielmi C. et al. Early administration of donor lymphocyte infusions upon molecular relapse after allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia: A study by the chronic malignancies working party of the EBMT. Haematologica. 2014; 99(9): 1492–8. DOI: 10.3324/haematol.2013.100198.Chalandon Y., Passweg J.R., Guglielmi C. et al. Early administration of donor lymphocyte infusions upon molecular relapse after allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia: A study by the chronic malignancies working party of the EBMT. Haematologica. 2014; 99(9): 1492–8. DOI: 10.3324/haematol.2013.100198.Basak G.W., De Wreede L.C., Van Biezen A. et al. Donor lymphocyte infusions for the treatment of chronic myeloid leukemia relapse following peripheral blood or bone marrow stem cell transplantation. Bone Marrow Transplant. 2013; 48(6): 837–42. DOI: 10.1038/bmt.2012.234.Basak G.W., De Wreede L.C., Van Biezen A. et al. Donor lymphocyte infusions for the treatment of chronic myeloid leukemia relapse following peripheral blood or bone marrow stem cell transplantation. Bone Marrow Transplant. 2013; 48(6): 837–42. DOI: 10.1038/bmt.2012.234.

The authors declare that there are no conflicts of interest present.