bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2020-65-4-483-500bloodjour-248Research ArticleКЛИНИЧЕСКИЕ НАБЛЮДЕНИЯCASE REPORTSПервый опыт трансплантации аллогенных гемопоэтических стволовых клеток у больных лимфомой из клеток мантии с мутациями в гене ТР53First experience of allogeneic haematopoietic stem cell transplantation in patients with mantle cell lymphoma with a mutation in the TP53 genehttps://orcid.org/0000-0001-5762-8294КоролеваД. А.KorolevaD. A.

Дарья Александровна Королева, гематолог отделения интенсивной высокодозной химиотерапии лимфом с круглосуточным и дневным стационаром

125167, Москвател.: +7 (495) 612-44-72 

Daria A. Koroleva, Hematologist, Department of Intensive High-Dose Chemotherapy for Lymphoma

125167, Moscowtel.: +7 (495) 612-44-72 

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

Нелли Георгиевна Габеева, кандидат медицинских наук, гематолог отделения интенсивной высокодозной химиотерапии лимфом с круглосуточным и дневным стационаром

125167, Москва

Nelli G. Gabeeva, Cand. Sci. (Med.), Hematologist, Department of Intensive High-Dose Chemotherapy for Lymphoma

125167, Moscow

dr.gabeeva@gmail.comhttps://orcid.org/0000-0001-9431-8316ДроковМ. Ю.DrokovM. Yu.

Дроков Михаил Юрьевич, кандидат медицинских наук, гематолог отделения интенсивной высокодозной химиотерапии и трансплантации костного мозга с круглосуточным и дневным стационаром, руководитель сектора по изучению иммунных воздействий и осложнений после ТКМ

125167, Москва

Mikhail Yu. Drokov, Cand. Sci. (Med.), Hematologist, Department of Intensive High-Dose Chemotherapy and Bone Marrow Transplantation; Head of the Department of Immunotherapy and Post-BMT Complications

125167, Moscow

mdrokov@gmail.comhttps://orcid.org/0000-0003-0904-7385ВасильеваВ. А.VasilyevaV. A.

Вера Алексеевна Васильева, кандидат медицинских наук, заведующая отделением иммунохимиотерапии с дневным стационаром для больных после ТКМ

125167, Москва

Vera A. Vasilyeva, Cand. Sci. (Med.), Head of the Department of Immunochemotherapy with Day BMT Hospital Unit

125167, Moscow

vasilievava4@mail.ruhttps://orcid.org/0000-0002-6253-3334БидерманБ. В.BidermanB. V.

Белла Вениаминовна Бидерман, кандидат биологических наук, старший научный сотрудник лаборатории молекулярной гематологии

125167, Москва

Bella V. Biderman, Cand. Sci. (Biol.), Senior Researcher, Laboratory of Molecular Hematology

125167, Moscow

bella_biderman@mail.ruhttps://orcid.org/0000-0003-1065-3702ЦыганковаС. В.TsygankovaS. V.

Светлана Валерьевна Цыганкова, кандидат биологических наук, старший научный сотрудник лаборатории палео- и этногенетики Курчатовского комплекса НБИКС-природноподобных технологий

123182, Москва

Svetlana V. Tsygankova, Cand. Sci. (Biol.), Senior Researcher, Laboratory of Paleo- and Ethnogenetics, NBICS Nature-like Technologies Complex

123182, Moscow

svetlana.tsygankova@gmail.comhttps://orcid.org/0000-0003-3795-0571БулыгинаЕ. С.BulyginaE. S.

Евгения Станиславовна Булыгина, кандидат биологических наук, ведущий научный сотрудник ресурсного центра молекулярно-клеточной биологии Курчатовского комплекса НБИКС-природоподобных технологий

123182, Москва

Evgeniya S. Bulygina, Cand. Sci. (Biol.), Leading Researcher, Resource Center for Molecular Cell Biology, NBICS Nature-like Technologies Complex

123182, Moscow

eugenia.bulygina@gmail.comhttps://orcid.org/0000-0001-8818-8949ГалстянГ. М.GalstyanG. M.

Геннадий Мартинович Галстян, доктор медицинских наук, заведующий отделением реанимации и интенсивной терапии

125167, Москва

Gennadiy M. Galstyan, Dr. Sci. (Med), Head of the Department of Resuscitation and Intensive Care

125167, Moscow

gengalst@gmail.comhttps://orcid.org/0000-0001-9463-9187СудариковА. Б.SudarikovA. B.

Андрей Борисович Судариков, доктор биологических наук, заведующий лабораторией молекулярной гематологии

125167, Москва

Andrey B. Sudarikov, Dr. Sci. (Biol.), Head of the Laboratory of Molecular Genetics

125167, Moscow

andrey@sudarikov.nethttps://orcid.org/0000-0003-1613-652XОбуховаТ. Н.ObukhovaT. N.

Татьяна Никифоровна Обухова, кандидат медицинских наук, заведующая лабораторией кариологии

125167, Москва

Tatyana N. Obukhova, Cand. Sci. (Med.), Head of the Laboratory of Karyology

125167, Moscow

obukhova_t@mail.ruhttps://orcid.org/0000-0001-6201-6276КузьминаЛ. А.KuzminaL. A.

Лариса Анатольевна Кузьмина, кандидат медицинских наук, заведующая отделением интенсивной высокодозной химиотерапии и трансплантации костного мозга с круглосуточным стационаром

125167, Москва

Larisa A. Kuzmina, Cand. Sci. (Med.), Department of Intensive High-Dose Chemotherapy and Bone Marrow Transplantation

125167, Moscow

kuzlara@rambler.ruhttps://orcid.org/0000-0002-2639-7419ЗвонковЕ. Е.ZvonkovE. E.

Евгений Евгеньевич Звонков, доктор медицинских наук, заведующий отделением высокодозной химиотерапии лимфом с круглосуточным стационаром

125167, Москва

Eugene E. Zvonkov, Dr. Sci. (Med.), Head of the Department of Intensive HighDose Chemotherapy for Lymphoma

125167, Moscow

dr.zvonkov@gmail.comhttps://orcid.org/0000-0001-6177-3566ПаровичниковаЕ. Н.ParovichnikovaE. N.

Елена Николаевна Паровичникова, доктор медицинских наук, заведующая отделом химиотерапии гемобластозов, депрессий кроветворения и трансплантации костного мозга

125167, Москва

Elena N. Parovichnikova, Dr. Sci. (Med.), Head of the Department of Chemotherapy of Hemoblastosis, Hematopoiesis Depression and Bone Marrow Transplantation

125167, Moscow

elenap@blood.ruhttps://orcid.org/0000-0001-8188-5557СавченкоВ. Г.SavchenkoV. G.

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

125167, Москва

Valeriy G. Savchenko, Dr. Sci. (Med.), Professor, Full Member of the Russian Academy of Sciences, Director

125167, Moscow

director@blood.ruФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Research Center for HematologyRussian FederationФГБУ «Национальный исследовательский центр «Курчатовский институт»»РоссияNational Research Center “Kurchatov institute”Russian Federation202009122020654483500Copyright © Королева Д.А., Габеева Н.Г., Дроков М.Ю., Васильева В.А., Бидерман Б.В., Цыганкова С.В., Булыгина Е.С., Галстян Г.М., Судариков А.Б., Обухова Т.Н., Кузьмина Л.А., Звонков Е.Е., Паровичникова Е.Н., Савченко В.Г., 20202020Королева Д.А., Габеева Н.Г., Дроков М.Ю., Васильева В.А., Бидерман Б.В., Цыганкова С.В., Булыгина Е.С., Галстян Г.М., Судариков А.Б., Обухова Т.Н., Кузьмина Л.А., Звонков Е.Е., Паровичникова Е.Н., Савченко В.Г.Koroleva D.A., Gabeeva N.G., Drokov M.Y., Vasilyeva V.A., Biderman B.V., Tsygankova S.V., Bulygina E.S., Galstyan G.M., Sudarikov A.B., Obukhova T.N., Kuzmina L.A., Zvonkov E.E., Parovichnikova E.N., 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/248Введение

Введение. Наличие мутаций в гене ТР53 у больных ЛКМ (ЛКМ ТР53+) ассоциировано с низкой чувствительностью к интенсивной химиотерапии, неблагоприятным исходом. Трансплантация аллогенных гемопоэтических стволовых клеток (алло-ТГСК) является методом, позволяющим добиться излечения больных ЛКМ TP53+.

Цель

Цель: оценить эффективность и переносимость алло-ТГСК у больных ЛКМ TP53+.

Основные сведения

Основные сведения. С 2016 по 2020 гг. алло-ТГСК была выполнена 3 больным ЛКМ ТР53+. Двоим больным алло-ТГСК была выполнена от HLA-идентичных неродственных доноров, 1 больному — от гаплоидентичного донора. Предтрансплантационное кондиционирование 1 больному было проведено по программе «флударабин + треосульфан + мелфалан», 2 больным по схеме «флударабин + бусульфан». У 3 больных восстановление количества лейкоцитов и тромбоцитов было отмечено на +18 и +20 дни; +17 и +21 дни; +19 и +16 дни после алло-ТГСК соответственно. Развитие острой реакции «трансплантат против хозяина» (РТПХ) было отмечено у всех больных (I степени — у 2 больных, IV степени — у 1 больного). У одной больной развилась хроническая РТПХ, средней степени. У всех 3 больных сохраняются полная ремиссия и 100%-ный донорский химеризм при сроке наблюдения 6, 15 и 40 месяцев после алло-ТГСК соответственно.

Introduction

Introduction. Mutations in the TP53 gene in patients with mantle cell lymphoma (MCL TP53+) are associated with a low response to intensive chemotherapy (CT) and adverse outcomes. Allogeneic haematopoietic stem cells transplantation (allo-HSCT) is a curative approach in MCL-TP53+ patients.

Aim

Aim. Efficacy and safety assessment of allo-HSCT in MCL-TP53+ patients.

Main findings

Main findings. During 2016–2020, allo-HSCT in MCL TP53+ was performed in three patients. Two of them were grafted from HLA-identical unrelated donors, and one — from a haploidentical donor. Pre-transplant conditioning was “fludarabine + treosulfan + melphalan” in one case, and “fludarabine + busulfan” — in the other two. In three patients, leukocyte and platelet counts were recovered at days +18 and +20, +17 and +21, +19 and +16 after allo-HSCT, respectively. Acute graft-versushost disease (aGVHD) was observed in all patients (grade I — in 2 patients, grade IV — in 1 patient). One patient developed chronic GVHD (cGVHD) of moderate grade. All three patients exhibited complete remission and 100% donor chimerism in allo-HSCT follow-up of 6, 15 and 40 months, respectively.

лимфома из клеток мантиимутация гена ТР53алло-ТГСКРТПХсеквенирование нового поколенияmantle cell lymphomamutation of TP53 geneallo-HCTGVHDnext generation sequencingReferencesSandoval-Sus J., Sotomayor E.M., Shah B.D. Mantle cell lymphoma: Contemporary diagnostic and treatment perspectives in the age of personalized medicine. Hematol Oncol Stem Cell Ther. 2017; 10(3): 99–115. DOI: 10.1016/j.hemonc.2017.02.003.Sandoval-Sus J., Sotomayor E.M., Shah B.D. Mantle cell lymphoma: Contemporary diagnostic and treatment perspectives in the age of personalized medicine. Hematol Oncol Stem Cell Ther. 2017; 10(3): 99–115. DOI: 10.1016/j.hemonc.2017.02.003.Geisler C.H., Kolstad A., Laurell A. et al. Nordic MCL2 trial update: Six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: Still very long survival but late relapses do occur. Br J Haematol. 2012; 158(3) :355–62. DOI: 10.1111/j.1365-2141.2012.09174.x.Geisler C.H., Kolstad A., Laurell A. et al. Nordic MCL2 trial update: Six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: Still very long survival but late relapses do occur. Br J Haematol. 2012; 158(3) :355–62. DOI: 10.1111/j.1365-2141.2012.09174.x.Eskelund C.W., Kolstad A., Jerkeman M. et al. 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau. Br J Haematol. 2016; 175(3): 410–8. DOI: 10.1111/bjh.14241.Eskelund C.W., Kolstad A., Jerkeman M. et al. 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau. Br J Haematol. 2016; 175(3): 410–8. DOI: 10.1111/bjh.14241.Dreyling M., Klapper W., Rule S. Blastoid and pleomorphic mantle cell lymphoma: Still a diagnostic and therapeutic challenge! Blood. 2018; 132(26): 2722–9. DOI: 10.1182/blood-2017-08-737502.Dreyling M., Klapper W., Rule S. Blastoid and pleomorphic mantle cell lymphoma: Still a diagnostic and therapeutic challenge! Blood. 2018; 132(26): 2722–9. DOI: 10.1182/blood-2017-08-737502.Eskelund C.W., Dahl C., Hansen J.W. et al. TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy. Blood. 2017; 130(17): 1903–10. DOI: 10.1182/blood-2017-04-779736.Eskelund C.W., Dahl C., Hansen J.W. et al. TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy. Blood. 2017; 130(17): 1903–10. DOI: 10.1182/blood-2017-04-779736.Young K.H., Leroy K., Møller M.B. et al. Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: An international collaborative study. Blood. 2008; 112(8): 3088–98. DOI: 10.1182/blood-2008-01-129783.Young K.H., Leroy K., Møller M.B. et al. Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: An international collaborative study. Blood. 2008; 112(8): 3088–98. DOI: 10.1182/blood-2008-01-129783.Tam C.S., Anderson M.A., Pott C. et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018; 378(13): 1211–23. DOI: 10.1056/NEJMoa1715519.Tam C.S., Anderson M.A., Pott C. et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018; 378(13): 1211–23. DOI: 10.1056/NEJMoa1715519.Agarwal R., Dawson M.A., Dreyling M. et al. Understanding resistance mechanisms to BTK and BCL2 inhibitors in mantle cell lymphoma: implications for design of clinical trials. Leuk Lymphoma. 2018; 59(12): 2769–81. DOI: 10.1080/10428194.2018.1457148.Agarwal R., Dawson M.A., Dreyling M. et al. Understanding resistance mechanisms to BTK and BCL2 inhibitors in mantle cell lymphoma: implications for design of clinical trials. Leuk Lymphoma. 2018; 59(12): 2769–81. DOI: 10.1080/10428194.2018.1457148.Lin R.J., Ho C., Hilden P.D. et al. Allogeneic haematopoietic cell transplantation impacts on outcomes of mantle cell lymphoma with TP53 alterations. Br J Haematol. 2019; 184(6): 1006–10. DOI: 10.1111/bjh.15721.Lin R.J., Ho C., Hilden P.D. et al. Allogeneic haematopoietic cell transplantation impacts on outcomes of mantle cell lymphoma with TP53 alterations. Br J Haematol. 2019; 184(6): 1006–10. DOI: 10.1111/bjh.15721.Dietrich S., Dreger P., Hermine O. et al. Haploidentical stem cell transplantation for patients with lymphoma: a position statement from the Lymphoma Working Party-European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2019; 55(2): 317–24. DOI: 10.1038/s41409-019-0583-4.Dietrich S., Dreger P., Hermine O. et al. Haploidentical stem cell transplantation for patients with lymphoma: a position statement from the Lymphoma Working Party-European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2019; 55(2): 317–24. DOI: 10.1038/s41409-019-0583-4.Hoster E., Dreyling M., Klapper W. et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 2008; 111(2): 558–65. DOI: 10.1182/blood-2007-06-095331.Hoster E., Dreyling M., Klapper W. et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 2008; 111(2): 558–65. DOI: 10.1182/blood-2007-06-095331.Воробьев В.И., Лорие Ю.Ю., Кравченко С.К. Протокол терапии лимфомы из клеток мантийной зоны у пациентов моложе 65 лет. Программное лечение заболеваний системы крови. М.: Практика, 2012; 619–40.Vorobyev V.I., Lorie Y.Y., Kravchenko S.K. Treatment protocol for mantle lymphoma in patients under 65 years. Programmatic treatment of blood diseases. Moscow: Praktika, 2012; 619–40 (In Russian).Королева Д.А., Звонков Е.Е., Габеева Н.Г. и др. Исследовательский протокол лечения лимфомы из клеток мантийной зоны у больных в возрасте до 65 лет. Алгоритмы диагностики и протоколы лечения заболеваний системы крови. 2018; 2: 531–56.Koroleva D.A., Zvonkov E.E., Gabeeva N.G., et al. Research treatment protocol for mantle lymphoma in patients under 65 years. Diagnostic algorithms and treatment protocols for blood diseases. Moscow: Praktika, 2018, 2: 531–55 (In Russian).Goyal R.K., Goyal M., Sankaranarayan K. Grading acute graft-versus-host disease: Time to reconsider. Pediatr Transplant. 2015; 19(3): 252–4. DOI: 10.1111/petr.12433.Goyal R.K., Goyal M., Sankaranarayan K. Grading acute graft-versus-host disease: Time to reconsider. Pediatr Transplant. 2015; 19(3): 252–4. DOI: 10.1111/petr.12433.Oken M.M., Creech R.H., Davis T.E. Toxicology and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 5: 649–55. DOI: 10.1097/00000421-198212000-00014.Oken M.M., Creech R.H., Davis T.E. Toxicology and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 5: 649–55. DOI: 10.1097/00000421-198212000-00014.Barrington S.F., Mikhaeel N.G., Kostakoglu L. et al. Role of imaging in the staging and response assessment of lymphoma: Consensus of the international conference on malignant lymphomas imaging working group. J Clin Oncol. 2014; 32(27): 3048–58. DOI: 10.1200/JCO.2013.53.5229.Barrington S.F., Mikhaeel N.G., Kostakoglu L. et al. Role of imaging in the staging and response assessment of lymphoma: Consensus of the international conference on malignant lymphomas imaging working group. J Clin Oncol. 2014; 32(27): 3048–58. DOI: 10.1200/JCO.2013.53.5229.Lee S.J. Classification systems for chronic graft-versus-host disease. Blood. 2017; 129(1): 30–7. DOI: 10.1182/blood-2016-07-686642.Lee S.J. Classification systems for chronic graft-versus-host disease. Blood. 2017; 129(1): 30–7. DOI: 10.1182/blood-2016-07-686642.Weisenburger D.D., Nathwani B.N., Diamond L.W. et al. Malignant lymphoma, intermediate lymphocytic type: a clinicopathologic study of 42 cases. Cancer. 1981; 48: 1415–25.Weisenburger D.D., Nathwani B.N., Diamond L.W. et al. Malignant lymphoma, intermediate lymphocytic type: a clinicopathologic study of 42 cases. Cancer. 1981; 48: 1415–25.Howard O.M., Gribben J.G., Neuberg D.S. et al. Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: Molecular complete responses are not predictive of progression-free survival. J Clin Oncol. 2002; 20(5): 1288–94. DOI: 10.1200/JCO.20.5.1288.Howard O.M., Gribben J.G., Neuberg D.S. et al. Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: Molecular complete responses are not predictive of progression-free survival. J Clin Oncol. 2002; 20(5): 1288–94. DOI: 10.1200/JCO.20.5.1288.Kumar A., Sha F., Toure A. et al. Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive shortening in response duration and survival after each relapse. Blood Cancer J. 2019; DOI: 10.1038/s41408-019-0209-5.Kumar A., Sha F., Toure A. et al. Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive shortening in response duration and survival after each relapse. Blood Cancer J. 2019; DOI: 10.1038/s41408-019-0209-5.Kröger N., Hoffknecht M., Krüger W. et al. Allogeneic bone marrow transplantation for lymphoma. Blood Rev. 2000; 14(1): 1–13. DOI: 10.1054/blre.1999.0125.Kröger N., Hoffknecht M., Krüger W. et al. Allogeneic bone marrow transplantation for lymphoma. Blood Rev. 2000; 14(1): 1–13. DOI: 10.1054/blre.1999.0125.Khouri I.F., Lee M.S., Romaguera J. et al. Allogeneic hematopoietic transplantation for mantle-cell lymphoma: Molecular remissions and evidence of graft-versus-malignancy. Ann Oncol. 1999; 10(11): 1293–9. DOI: 10.1023/A:1008380527502.Khouri I.F., Lee M.S., Romaguera J. et al. Allogeneic hematopoietic transplantation for mantle-cell lymphoma: Molecular remissions and evidence of graft-versus-malignancy. Ann Oncol. 1999; 10(11): 1293–9. DOI: 10.1023/A:1008380527502.Khouri I.F., Lee M.S., Saliba R.M. et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol. 2003; 21(23): 4407–12. DOI: 10.1200/JCO.2003.05.501.Khouri I.F., Lee M.S., Saliba R.M. et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol. 2003; 21(23): 4407–12. DOI: 10.1200/JCO.2003.05.501.Robinson S.P., Goldstone A.H., Mackinnon S. et al. Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Br J Haematol. 2000; 110(1): 12–7. DOI: 10.1046/j.1365-2141.2000.02075.x.Robinson S.P., Goldstone A.H., Mackinnon S. et al. Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Br J Haematol. 2000; 110(1): 12–7. DOI: 10.1046/j.1365-2141.2000.02075.x.Tam C.S., Bassett R., Ledesma C. et al. Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma. Blood. 2009; 113(18): 4144–52. DOI: 10.1182/blood-2008-10-184200.Tam C.S., Bassett R., Ledesma C. et al. Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma. Blood. 2009; 113(18): 4144–52. DOI: 10.1182/blood-2008-10-184200.Kharfan-Dabaja M.A., Reljic T., El-Asmar J. et al. Reduced-intensity or myeloablative allogeneic hematopoietic cell transplantation for mantle cell lymphoma: A systematic review. Futur Oncol. 2016; 12(22): 2631–42. DOI: 10.2217/fon-2016-0146.Kharfan-Dabaja M.A., Reljic T., El-Asmar J. et al. Reduced-intensity or myeloablative allogeneic hematopoietic cell transplantation for mantle cell lymphoma: A systematic review. Futur Oncol. 2016; 12(22): 2631–42. DOI: 10.2217/fon-2016-0146.Duarte R.F., Labopin M., Bader P. et al. Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019. Bone Marrow Transplant. 2019; 54(10): 1525–52. DOI: 10.1038/s41409-019-0516-2.Duarte R.F., Labopin M., Bader P. et al. Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019. Bone Marrow Transplant. 2019; 54(10): 1525–52. DOI: 10.1038/s41409-019-0516-2.Fenske T.S., Zhang M.J., Carreras J. et al. Autologous or reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chemotherapy-sensitive mantle-cell lymphoma: Analysis of transplantation timing and modality. J Clin Oncol. 2014; 32(4): 273–81. DOI: 10.1200/JCO.2013.49.2454.Fenske T.S., Zhang M.J., Carreras J. et al. Autologous or reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chemotherapy-sensitive mantle-cell lymphoma: Analysis of transplantation timing and modality. J Clin Oncol. 2014; 32(4): 273–81. DOI: 10.1200/JCO.2013.49.2454.Krüger W.H., Hirt C., Basara N. et al. Allogeneic stem cell transplantation for mantle cell lymphoma—Final report from the prospective trials of the East German Study Group Haematology/Oncology (OSHO). Ann Hematol. 2014; 93(9): 1587–97. DOI: 10.1007/s00277-014-2087-z.Krüger W.H., Hirt C., Basara N. et al. Allogeneic stem cell transplantation for mantle cell lymphoma—Final report from the prospective trials of the East German Study Group Haematology/Oncology (OSHO). Ann Hematol. 2014; 93(9): 1587–97. DOI: 10.1007/s00277-014-2087-z.Rule S., Cook G., Russell N.H. et al. Allogeneic stem cell transplantation as part of front line therapy for Mantle cell lymphoma. Br J Haematol. 2019; 184(6): 999–1005. DOI: 10.1111/bjh.15723.Rule S., Cook G., Russell N.H. et al. Allogeneic stem cell transplantation as part of front line therapy for Mantle cell lymphoma. Br J Haematol. 2019; 184(6): 999–1005. DOI: 10.1111/bjh.15723.Sandoval-Sus J.D., Faramand R., Chavez J. et al. Allogeneic hematopoietic cell transplantation is potentially curative in mantle cell lymphoma: results from a single institution study. Leuk Lymphoma. 2019; 60(2): 309–16. DOI: 10.1080/10428194.2018.1468894.Sandoval-Sus J.D., Faramand R., Chavez J. et al. Allogeneic hematopoietic cell transplantation is potentially curative in mantle cell lymphoma: results from a single institution study. Leuk Lymphoma. 2019; 60(2): 309–16. DOI: 10.1080/10428194.2018.1468894.Lachance S., Molucon-Chabrot C., Busque L. et al. First line allogeneic stem cell transplantation in mantle cell lymphoma (MCL). Blood. 2009; 114: 3366. DOI: 10.1182/blood.v114.22.3366.3366.Lachance S., Molucon-Chabrot C., Busque L. et al. First line allogeneic stem cell transplantation in mantle cell lymphoma (MCL). Blood. 2009; 114: 3366. DOI: 10.1182/blood.v114.22.3366.3366.Xu-Monette Z.Y., Jeffrey Medeiros L., Li Y. et al. Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies. Blood. 2012; 119(16): 3668–83. DOI: 10.1182/blood-2011-11-366062.Xu-Monette Z.Y., Jeffrey Medeiros L., Li Y. et al. Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies. Blood. 2012; 119(16): 3668–83. DOI: 10.1182/blood-2011-11-366062.Cortelazzo S., Ponzoni M. Mantle cell lymphoma. Oncol Hamatol. 2020; DOI: 10.1016/j.critrevonc.2020.103038.Cortelazzo S., Ponzoni M. Mantle cell lymphoma. Oncol Hamatol. 2020; DOI: 10.1016/j.critrevonc.2020.103038.Rule S., Dreyling M., Goy A. et al. Ibrutinib for the treatment of relapsed/ refractory mantle cell lymphoma: Extended 3.5-year follow up from a pooled analysis. Haematologica. 2019; 104(5): e211–4. DOI: 10.3324/haematol.2018.205229.Rule S., Dreyling M., Goy A. et al. Ibrutinib for the treatment of relapsed/ refractory mantle cell lymphoma: Extended 3.5-year follow up from a pooled analysis. Haematologica. 2019; 104(5): e211–4. DOI: 10.3324/haematol.2018.205229.Dreyling M., Jurczak W., Jerkeman M. et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: An international, randomised, open-label, phase 3 study. Lancet. 2016; 387(10020): 770–8. DOI: 10.1016/S0140-6736(15)00667-4.Dreyling M., Jurczak W., Jerkeman M. et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: An international, randomised, open-label, phase 3 study. Lancet. 2016; 387(10020): 770–8. DOI: 10.1016/S0140-6736(15)00667-4.Wang M., Jain P., Lee H.L. et al. Frontline treatment with ibrutinib plus rituximab (IR) followed by short course R-Hypercvad/MTX is extremely potent and safe in patients (age ≤ 65 years) with mantle cell lymphoma (MCL)—results of phaseII window-1 clinical trial. Blood. 2019, 134(Suppl. 1): 3987. DOI: 10.1182/blood-2019-126044.Wang M., Jain P., Lee H.L. et al. Frontline treatment with ibrutinib plus rituximab (IR) followed by short course R-Hypercvad/MTX is extremely potent and safe in patients (age ≤ 65 years) with mantle cell lymphoma (MCL)—results of phaseII window-1 clinical trial. Blood. 2019, 134(Suppl. 1): 3987. DOI: 10.1182/blood-2019-126044.Davids M.S., Roberts A.W., Seymour J.F. et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-hodgkin lymphoma. J Clin Oncol. 2017; 35(8): 826–33. DOI: 10.1200/JCO.2016.70.4320.Davids M.S., Roberts A.W., Seymour J.F. et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-hodgkin lymphoma. J Clin Oncol. 2017; 35(8): 826–33. DOI: 10.1200/JCO.2016.70.4320.Jelinek T., Mihalyova J., Kascak M. et al. Single-agent venetoclax induces MRD-negative response in relapsed primary plasma cell leukemia with t(11;14). Am J Hematol. 2019; 94(1): E35–7. DOI: 10.1002/ajh.25331.Jelinek T., Mihalyova J., Kascak M. et al. Single-agent venetoclax induces MRD-negative response in relapsed primary plasma cell leukemia with t(11;14). Am J Hematol. 2019; 94(1): E35–7. DOI: 10.1002/ajh.25331.Sun M., Zhang H. Therapeutic antibodies for mantle cell lymphoma: A brand-new era ahead. Heliyon. 2019; 5(3): e01297. DOI: 10.1016/j.heliyon.2019.e01297.Sun M., Zhang H. Therapeutic antibodies for mantle cell lymphoma: A brand-new era ahead. Heliyon. 2019; 5(3): e01297. DOI: 10.1016/j.heliyon.2019.e01297.Wang M., Schuster S.J., Phillips T. et al. Observational study of lenalidomide in patients with mantle cell lymphoma who relapsed/progressed after or were refractory/intolerant to ibrutinib (MCL-004). J Hematol Oncol. 2017; 10(1): 1–8. DOI: 10.1186/s13045-017-0537-5.Wang M., Schuster S.J., Phillips T. et al. Observational study of lenalidomide in patients with mantle cell lymphoma who relapsed/progressed after or were refractory/intolerant to ibrutinib (MCL-004). J Hematol Oncol. 2017; 10(1): 1–8. DOI: 10.1186/s13045-017-0537-5.Goy A., Sinha R., Williams M.E. et al. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: Phase II MCL-001 (EMERGE) study. J Clin Oncol. 2013; 31(29): 3688–95. DOI: 10.1200/JCO.2013.49.2835.Goy A., Sinha R., Williams M.E. et al. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: Phase II MCL-001 (EMERGE) study. J Clin Oncol. 2013; 31(29): 3688–95. DOI: 10.1200/JCO.2013.49.2835.Morabito F., Skafi M., Recchia A.G. et al. Lenalidomide for the treatment of mantle cell lymphoma. Expert Opin Pharmacother. 2019; 20(5): 487–94. DOI: 10.1080/14656566.2018.1561865.Morabito F., Skafi M., Recchia A.G. et al. Lenalidomide for the treatment of mantle cell lymphoma. Expert Opin Pharmacother. 2019; 20(5): 487–94. DOI: 10.1080/14656566.2018.1561865.Dreger P., Michallet M., Bosman P. et al. Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties. Bone Marrow Transplant. 2019; 54(1): 44–52. DOI: 10.1038/s41409-018-0207-4.Dreger P., Michallet M., Bosman P. et al. Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties. Bone Marrow Transplant. 2019; 54(1): 44–52. DOI: 10.1038/s41409-018-0207-4.Jerkeman M., Eskelund C.W., Hutchings M. et al. Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. Lancet Haematol. 2018; 5(3): e109–16. DOI: 10.1016/S2352-3026(18)30018-8.Jerkeman M., Eskelund C.W., Hutchings M. et al. Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. Lancet Haematol. 2018; 5(3): e109–16. DOI: 10.1016/S2352-3026(18)30018-8.Ghosh N., Karmali R., Rocha V. et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: A center for international blood and marrow transplant research analysis. J Clin Oncol. 2016; 34(26): 3141–9. DOI: 10.1200/JCO.2015.66.3476.Ghosh N., Karmali R., Rocha V. et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: A center for international blood and marrow transplant research analysis. J Clin Oncol. 2016; 34(26): 3141–9. DOI: 10.1200/JCO.2015.66.3476.Kanate A.S., Mussetti A., Kharfan-Dabaja M.A. et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLAmatched unrelated donors. Blood. 2016; 127(7): 938–47. DOI: 10.1182/blood-2015-09-671834.Kanate A.S., Mussetti A., Kharfan-Dabaja M.A. et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLAmatched unrelated donors. Blood. 2016; 127(7): 938–47. DOI: 10.1182/blood-2015-09-671834.De Philippis C., Mariotti J., Bouabdallah R. et al. Haploidentical allogeneic hematopoietic cell transplantation for mantle cell lymphoma using post-transplantation cyclophosphamide graft-versus-host disease prophylaxis. Blood. 2018; 132: 5748. DOI: 10.1182/blood-2018-99-117005.De Philippis C., Mariotti J., Bouabdallah R. et al. Haploidentical allogeneic hematopoietic cell transplantation for mantle cell lymphoma using post-transplantation cyclophosphamide graft-versus-host disease prophylaxis. Blood. 2018; 132: 5748. DOI: 10.1182/blood-2018-99-117005.Beà S., Valdés-Mas R., Navarro A. et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc Natl Acad Sci USA. 2013; 110(45): 18250–5. DOI: 10.1073/pnas.1314608110.Beà S., Valdés-Mas R., Navarro A. et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc Natl Acad Sci USA. 2013; 110(45): 18250–5. DOI: 10.1073/pnas.1314608110.Ferrero S., Rossi D., Rinaldi A. et al. KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study. Haematologica. 2020; 105(6): 1604–12. DOI: 10.3324/haematol.2018.214056.Ferrero S., Rossi D., Rinaldi A. et al. KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study. Haematologica. 2020; 105(6): 1604–12. DOI: 10.3324/haematol.2018.214056.

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