bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2024-69-4-463-473bloodjour-598Research ArticleОБЗОРЫREVIEWSТерапия рефрактерных и рецидивирующих Т-лимфобластных лимфом из клеток-предшественниц у детей и подростков: современное состояние проблемы и перспективы дальнейших исследованийTreatment of refractory and recurrent T-lymphoblastic lymphomas from progenitor cells in children and adolescents: current problem state and future perspectiveshttps://orcid.org/0000-0003-4999-5195ПавловаТ. Ю.PavlovaT. Yu.

Павлова Татьяна Юрьевна, гематолог отделения детской онкологии и гематологии (химиотерапии гемобластозов) № 1 НИИ детской онкологии и гематологии

115522, г. Москва

Tatyana Y. Pavlova, Hematologist of the Department of Pediatric Oncology and Hematology (Hemoblastosis Chemotherapy) No. 1

115522, Moscow

md.pavlovaty@mail.ruhttps://orcid.org/0000-0002-1469-2365ВалиевТ. Т.ValievT. T.

Валиев Тимур Теймуразович, доктор медицинских наук, заведующий отделением детской онкологии и гематологии (химиотерапии гемобластозов) № 1 НИИ детской онкологии и гематологии; профессор кафедры детской онкологии имени акад. Л.А. Дурнова

115522, г. Москва; 125993, г. Москва

Timur T. Valiev, Dr. Sci. (Med.), Head of the Department of Pediatric Oncology and Hematology (Chemotherapy of Hemoblastosis) No1, Research Institute of Pediatric Oncology and Hematology; Professor of the Department of Pediatric Oncology named after Academician L.A. Durnov

115522, Moscow; 125993, Moscow

timurvaliev@mail.ruВарфоломееваС. Р.VarfolomeevaS. R.

Варфоломеева Светлана Рафаэлевна, доктор медицинских наук, профессор, директор НИИ детской онкологии и гематологии

115522, г. Москва

Svetlana R. Varfolomeeva, Dr. Sci. (Med.), Professor, Director of the Research Institute of Pediatric Oncology and Hematology

115522, Moscow

s.varfolomeeva@ronc.ruНИИ детской онкологии и гематологии ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Министерства здравоохранения Российской ФедерацииРоссияPediatric Oncology and Hematology Research Institute of N.N. Blokhin National Medical Research Center of OncologyRussian FederationНИИ детской онкологии и гематологии ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Министерства здравоохранения Российской Федерации; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияPediatric Oncology and Hematology Research Institute of N.N. Blokhin National Medical Research Center of Oncology; Russian Medical Academy of Continuous Professional EducationRussian Federation202428122024694463473Copyright © Павлова Т.Ю., Валиев Т.Т., Варфоломеева С.Р., 20242024Павлова Т.Ю., Валиев Т.Т., Варфоломеева С.Р.Pavlova T.Y., Valiev T.T., Varfolomeeva S.R.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/598Введение

Введение. Несмотря на достигнутые успехи в терапии лимфобластных лимфом из клеток-предшественниц (ЛБЛ), важной задачей остается улучшение показателей выживаемости в группе больных Т-клеточными лимфобластными лимфомами (Т-ЛБЛ). Группу особого неблагоприятного прогноза составляют больные с рецидивами и рефрактерными формами (Р/Р) Т-ЛБЛ.

Цель  — обзор литературы, посвященной использованию таргетных и  иммунных препаратов, а  также клеточных и трансплантационных методов в лечении Р/Р Т-ЛБЛ.

Основные сведения

Основные сведения. Современная клиническая онкогематология располагает широким арсеналом методов для лечения Р/Р Т-ЛБЛ, включающих интенсивные химиотерапевтические схемы, таргетные, трансплантационные технологии и терапию Т-лимфоцитами с химерным антигенным рецептором, но даже их сочетание в настоящее время не позволяет добиться оптимистичных результатов в данной прогностически неблагоприятной группе больных. Возможно, создание таргетных препаратов, направленных на сигнальные пути с участием NOTCH, PI3K/AKТ/mTOR, JAK/STAT и  MAPK, в  сочетании с  имеющимися терапевтическими возможностями позволит улучшить показатели выживаемости больных.

Introduction

Introduction. Despite the successes achieved in the treatment of lymphoblastic lymphomas from progenitor cells (LBL), an important task in improving survival rates in the group of patients with T-cell lymphoblastic lymphomas (T-LBL) remains. The group of special unfavorable prognosis consists of patients with relapses and refractory forms (r/r) of T-LBL.

Aim

Aim: to present a literature review on the use of targeted and immune drugs, as well as cellular and transplant methods in the treatment of r/r T-LBL.

Main findings

Main findings. Modern clinical onco-hematology has a broad spectrum of methods for the treatment of r/r T-LBL, including intensive chemotherapy, targeted, transplant and CAR-T technologies, but even a combination of these methods, currently, does not make it possible to achieve optimistic results in this prognostically unfavorable group of patients. It is possible that the creation of targeted drugs focused on signaling pathways (NOTCH, PI3K/ACT/mTOR, JAK/STAT and MAPK) with modern therapeutic potential could improve patient survival rates.

Т-клеточные лимфобластные лимфомыострый лимфобластный лейкозмолекулярно-генетический профильиммунотерапияCD7+ СAR-T-клеточная терапиядетиT-cell lymphoblastic lymphomasacute lymphoblastic leukemiamolecular genetic profileimmunotherapyCD7+ СAR-T-cell therapychildrenИсследование не имело спонсорской поддержки.The study had no financial support.ReferencesAlaggio R., Amador C., Anagnostopoulos I., et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022 Jul; 36(7): 1720–48. DOI: 10.1038/s41375-022-01620-2.Alaggio R., Amador C., Anagnostopoulos I., et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022 Jul; 36(7): 1720–48. DOI: 10.1038/s41375-022-01620-2.Oschlies I., Burkhardt B., Chassagne-Clement С., et al. Diagnosis and immunophenotype of 188 pediatric lymphoblastic lymphomas treated within a randomized prospective trial: experiences and preliminary recommendations from the European childhood lymphoma pathology panel. Am J Surg Pathol. 2011; 35(6): 836–44. DOI: 10.1097/PAS.0b013e318213e90e.Oschlies I., Burkhardt B., Chassagne-Clement С., et al. Diagnosis and immunophenotype of 188 pediatric lymphoblastic lymphomas treated within a randomized prospective trial: experiences and preliminary recommendations from the European childhood lymphoma pathology panel. Am J Surg Pathol. 2011; 35(6): 836–44. DOI: 10.1097/PAS.0b013e318213e90e.Béné M.C., Nebe T., Bettelheim P., et al. Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10. Leukemia. 2011; 25(4): 567–74. DOI: 10.1038/leu.2010.312.Béné M.C., Nebe T., Bettelheim P., et al. Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10. Leukemia. 2011;25(4):567-74. DOI: 10.1038/leu.2010.312.Béné M.C., Castoldi G., Knapp W., et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995; 9(10): 1783–6.Béné M.C., Castoldi G., Knapp W., et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995;9(10):1783-6.Dworzak M.N., Buldini B., Gaipa G., et al. International-BFM-FLOW-network. AIEOP-BFM consensus guidelines 2016 for flow cytometric immunophenotyping of Pediatric acute lymphoblastic leukemia. Cytometry B Clin Cytom. 2018; 94(1): 82–93. DOI: 10.1002/cyto.b.21518.Dworzak M.N., Buldini B., Gaipa G. et al. International-BFM-FLOW-network. AIEOP-BFM consensus guidelines 2016 for flow cytometric immunophenotyping of Pediatricacute lymphoblastic leukemia. Cytometry B Clin Cytom. 2018;94(1):82-93. DOI: 10.1002/cyto.b.21518.Vardiman J.W., Thiele J., Arber D.A., et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009; 114(5): 937–51. DOI: 10.1182/blood-2009-03-209262.Vardiman J.W., Thiele J., Arber D.A., et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009; 114(5): 937–51. DOI: 10.1182/blood-2009-03-209262.Temple W.C., Mueller S., Hermiston M.L., et al. Diagnosis and management of lymphoblastic lymphoma in children, adolescents and young adults. Best Pract Res Clin Haematol. 2023; 36(1): 101449. DOI: 10.1016/j.beha.2023.101449.Temple W.C., Mueller S., Hermiston M.L., et al. Diagnosis and management of lymphoblastic lymphoma in children, adolescents and young adults. Best Pract Res Clin Haematol. 2023; 36(1): 101449. DOI: 10.1016/j.beha.2023.101449.Lones, M.A., Heerema, N.A., Le Beau, et al. (2007) Chromosome abnormalities in advanced stage lymphoblastic lymphoma of children and adolescents: a report from CCG-E08. Cancer Genetics and Cytogenetics. 172: 1–11.Lones, M.A., Heerema, N.A., Le Beau, et al. (2007) Chromosome abnormalities in advanced stage lymphoblastic lymphoma of children and adolescents: a report from CCG-E08. Cancer Genetics and Cytogenetics. 172: 1–11.Basso K., Mussolin L., Lettieri A., et al. T-cell lymphoblastic lymphoma shows differences and similarities with T-cell acute lymphoblastic leukemia by genomic and gene expression analyses. Genes Chromosomes and Cancer. 2011; 50: 1063–75.Basso K., Mussolin L., Lettieri A., et al. T-cell lymphoblastic lymphoma shows differences and similarities with T-cell acute lymphoblastic leukemia by genomic and gene expression analyses. Genes Chromosomes and Cancer. 2011; 50: 1063–75.Feng H., Stachura D.L., White R.M., at el. T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell. 2010; 18(4): 353–66. DOI: 10.1016/j.ccr.2010.09.009.Feng H., Stachura D.L., White R.M., at el. T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell. 2010; 18(4): 353–66. DOI: 10.1016/j.ccr.2010.09.009.Callens C., Baleydier F., Lengline E., et al. Clinical impact of NOTCH1 and/ or FBXW7 mutations, FLASH deletion, and TCR status in pediatric T-cell lymphoblastic lymphoma. J Clin Oncol. 2012; 30(16): 1966–73. DOI: 10.1200/JCO.2011.39.7661.Callens C., Baleydier F., Lengline E., et al. Clinical impact of NOTCH1 and/ or FBXW7 mutations, FLASH deletion, and TCR status in pediatric T-cell lymphoblastic lymphoma. J Clin Oncol. 2012; 30(16): 1966–73. DOI: 10.1200/JCO.2011.39.7661.Ben A.R., Asnafi V., Leguay T., et al. Group for Research on Adult Acute Lymphoblastic Leukemia. Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/ BAALC expression: a GRAALL study. Blood. 2011; 118(19): 5099–107. DOI: 10.1182/blood-2011-02-334219.Ben A.R., Asnafi V., Leguay T., et al. Group for Research on Adult Acute Lymphoblastic Leukemia. Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/ BAALC expression: a GRAALL study. Blood. 2011; 118(19): 5099–107. DOI: 10.1182/blood-2011-02-334219.Burkhardt B., Bruch J., Zimmermann M., et al. Loss of heterozygosity on chromosome 6q14-q24 is associated with poor outcome in children and adolescents with T-cell lymphoblastic lymphoma. Leukemia. 2006; 20(8): 1422–9. DOI: 10.1038/sj.leu.2404275.Burkhardt B., Bruch J., Zimmermann M., et al. Loss of heterozygosity on chromosome 6q14-q24 is associated with poor outcome in children and adolescents with T-cell lymphoblastic lymphoma. Leukemia. 2006; 20(8): 1422–9. DOI: 10.1038/sj.leu.2404275.Burkhardt B., Moericke A., Klapper W., et al. Pediatric precursor T lymphoblastic leukemia and lymphoblastic lymphoma: Differences in the common regions with loss of heterozygosity at chromosome 6q and their prognostic impact. Leuk Lymphoma. 2008; 49(3): 451–61. DOI: 10.1080/10428190701824551.Burkhardt B., Moericke A., Klapper W., et al. Pediatric precursor T lymphoblastic leukemia and lymphoblastic lymphoma: Differences in the common regions with loss of heterozygosity at chromosome 6q and their prognostic impact. Leuk Lymphoma. 2008; 49(3): 451–61. DOI: 10.1080/10428190701824551.Veltri G., Lovisa F., Cortese G., et al. Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic Leukemia. Front Oncol. 2022; 12: 913487. DOI: 10.3389/fonc.2022.913487.Veltri G., Lovisa F., Cortese G., et al. Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic Leukemia. Front Oncol. 2022; 12: 913487. DOI: 10.3389/fonc.2022.913487.Burkhardt B., Hermiston M.L. Lymphoblastic lymphoma in children and adolescents: review of current challenges and future opportunities. Br J Haematol. 2019; 185(6): 1158–70. DOI: 10.1111/bjh.15793.Burkhardt B., Hermiston M.L. Lymphoblastic lymphoma in children and adolescents: review of current challenges and future opportunities. Br J Haematol. 2019; 185(6): 1158–70. DOI: 10.1111/bjh.15793.Алешина О.А., Гальцева И.В., Котова Е.С. и др. Результаты терапии острых Т-лимфобластных лейкозов/лимфом: данные многоцентрового проспективного рандомизированного исследования ОЛЛ -2016. Онкогематология. 2023; 18(1): 20–30. DOI: 10.17650/1818-8346-2023-18-1-20-30.Aleshina O.A., Galtseva I.V., Kotova E.S., et al. Treatment outcomes for acute T-lymphoblastic leukemias/lymphomas: data from the ALL-2016 multicenter prospective randomized trial. Onkogematologiya. 2023; 18(1): 20–30 (In Russian). DOI: 10.17650/1818-8346-2023-18-1-20-30.Schmidt E., Burkhardt B. Lymphoblastic lymphoma in childhood and adolescence. Pediatr Hematol Oncol. 2013; 30(6): 484–508. DOI: 10.3109/08880018.2013.789574.Schmidt E., Burkhardt B. Lymphoblastic lymphoma in childhood and adolescence. Pediatr Hematol Oncol. 2013; 30(6): 484–508. DOI: 10.3109/08880018.2013.789574.Cohen M.H., Johnson J.R., Justice R., et al. FDA drug approval summary: nelarabine (Arranon) for the treatment of T-cell lymphoblastic leukemia/lymphoma. Oncologist. 2008; 13(6): 709–14. DOI: 10.1634/theoncologist.2006-0017.Cohen M.H., Johnson J.R., Justice R., et al. FDA drug approval summary: nelarabine (Arranon) for the treatment of T-cell lymphoblastic leukemia/lymphoma. Oncologist. 2008; 13(6): 709–14. DOI: 10.1634/theoncologist.2006-0017.Гаврилина О.А., Котова Е.С., Паровичникова Е.Н. и др. Применение неларабина у взрослых больных с рефрактерным течением / рецидивом острого Т-лимфобластного лейкоза / лимфомы: опыт одного центра. Гематология и трансфузиология. 2019; 64(4): 382–95. DOI: 10.35754/0234-5730-2019-64-4-382-395.Gavrilina O.A., Kotova E.S., Parovichnikova E.N., et al. Nelarabine treatment in adult patients with refractory/relapsed T-cell acute lymphoblastic leukaemia/ lymphoma: experience of a single centre. Gematologiya i transfuziologiya. 2019; 64(4): 382–95 (In Russian). DOI: 10.35754/0234-5730-2019-64-4-382-395.Candoni A., Lazzarotto D., Ferrara F., et al. Nelarabine as salvage therapy and bridge to allogeneic stem cell transplant in 118 adult patients with relapsed/ refractory T-cell acute lymphoblastic leukemia/lymphoma. A CAMPUS ALL study. Am J Hematol. 2020; 95(12): 1466–72. DOI: 10.1002/ajh.25957.Candoni A., Lazzarotto D., Ferrara F., et al. Nelarabine as salvage therapy and bridge to allogeneic stem cell transplant in 118 adult patients with relapsed/ refractory T-cell acute lymphoblastic leukemia/lymphoma. A CAMPUS ALL study. Am J Hematol. 2020; 95(12): 1466–72. DOI: 10.1002/ajh.25957.Delgado-Martin C., Meyer L.K., Huang B.J., et al. JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias. Leukemia. 2017; 31(12): 2568–76. DOI: 10.1038/leu.2017.136.Delgado-Martin C., Meyer L.K., Huang B.J., et al. JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias. Leukemia. 2017; 31(12): 2568–76. DOI: 10.1038/leu.2017.136.Hui Shi, Kai Hu. Daratumumab-Primed Venetoclax Combined with Cage for Refractory/Relapsed T-Lymphoblastic Leukemia/Lymphoma Patients: SingleArm, Open-Label, Phase I Study. Blood. 2022; 140(Suppl. 1): 9480–1. DOI: 10.1182/blood-2022-165210.Hui Shi, Kai Hu. Daratumumab-Primed Venetoclax Combined with Cage for Refractory/Relapsed T-Lymphoblastic Leukemia/Lymphoma Patients: SingleArm, Open-Label, Phase I Study. Blood. 2022; 140(Suppl. 1): 9480–1. DOI: 10.1182/blood-2022-165210.Polgárová K., Otáhal P., Šálek C., et al. Chimeric Antigen Receptor Based Cellular Therapy for Treatment Of T-Cell Malignancies. Front Oncol. 2022; 12: 876758. DOI: 10.3389/fonc.2022.876758.Polgárová K., Otáhal P., Šálek C., et al. Chimeric Antigen Receptor Based Cellular Therapy for Treatment Of T-Cell Malignancies. Front Oncol. 2022; 12: 876758. DOI: 10.3389/fonc.2022.876758.De Smedt R., Peirs S., Morscio J., et al. Pre-clinical evaluation of second generation PIM inhibitors for the treatment of T-cell acute lymphoblastic leukemia and lymphoma. Haematologica. 2019; 104(1): e17–20. DOI: 10.3324/haematol.2018.199257.De Smedt R., Peirs S., Morscio J., et al. Pre-clinical evaluation of second generation PIM inhibitors for the treatment of T-cell acute lymphoblastic leukemia and lymphoma. Haematologica. 2019; 104(1): e17–20. DOI: 10.3324/haematol.2018.199257.Angiolillo A.L., Yu A.L., Reaman G., et al. A phase II study of Campath-1H in children with relapsed or refractory acute lymphoblastic leukemia: a Children’s Oncology Group report. Pediatr Blood Cancer. 2009; 53(6): 978–83. DOI: 10.1002/pbc.22209.Angiolillo A.L., Yu A.L., Reaman G., et al. A phase II study of Campath-1H in children with relapsed or refractory acute lymphoblastic leukemia: a Children’s Oncology Group report. Pediatr Blood Cancer. 2009; 53(6): 978–83. DOI: 10.1002/pbc.22209.Zheng W., Medeiros L.J., Young K.H., et al. CD30 expression in acute lymphoblastic leukemia as assessed by flow cytometry analysis. Leuk Lymphoma. 2014; 55(3): 624–7. DOI: 10.3109/10428194.2013.820293.Zheng W., Medeiros L.J., Young K.H., et al. CD30 expression in acute lymphoblastic leukemia as assessed by flow cytometry analysis. Leuk Lymphoma. 2014; 55(3): 624–7. DOI: 10.3109/10428194.2013.820293.DiNardo C.D., Lachowiez C.A., Takahashi K., et al. Venetoclax Combined With FLAG-IDA Induction and Consolidation in Newly Diagnosed and Relapsed or Refractory Acute Myeloid Leukemia. J Clin Oncol. 2021; 39(25): 2768–78. DOI: 10.1200/JCO.20.03736.DiNardo C.D., Lachowiez C.A., Takahashi K., et al. Venetoclax Combined With FLAG-IDA Induction and Consolidation in Newly Diagnosed and Relapsed or Refractory Acute Myeloid Leukemia. J Clin Oncol. 2021; 39(25): 2768–78. DOI: 10.1200/JCO.20.03736.Gibson A., Trabal A., McCall D., et al. Venetoclax for Children and Adolescents with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. Cancers (Basel). 2021; 14(1): 150. DOI: 10.3390/cancers14010150.Gibson A., Trabal A., McCall D., et al. Venetoclax for Children and Adolescents with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. Cancers (Basel). 2021; 14(1): 150. DOI: 10.3390/cancers14010150.Pullarkat V.A., Lacayo N.J., Jabbour E., et al. Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. Cancer Discov. 2021; 11(6): 1440–53. DOI: 10.1158/2159-8290.CD-20-1465.Pullarkat V.A., Lacayo N.J., Jabbour E., et al. Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. Cancer Discov. 2021; 11(6): 1440–53. DOI: 10.1158/2159-8290.CD-20-1465.Rahmat L.T., Nguyen A., Abdulhaq H., et al. Venetoclax in Combination with Decitabine for Relapsed T-Cell Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Cell Transplant. Case Rep. Hematol. 2018; 2018: 6092646. DOI: 10.1155/2018/6092646.Rahmat L.T., Nguyen A., Abdulhaq H., et al. Venetoclax in Combination with Decitabine for Relapsed T-Cell Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Cell Transplant. Case Rep. Hematol. 2018; 2018: 6092646. DOI: 10.1155/2018/6092646.Farhadfar N., Li Y., May W.S., et al. Venetoclax and Decitabine for Treatment of Relapsed T-Cell Acute Lymphoblastic Leukemia: A Case Report and Review of Literature. Hematol. Oncol. Stem Cell Ther. 2021; 14: 246–51. DOI: 10.1016/j.hemonc.2019.10.002.Farhadfar N., Li Y., May W.S., et al. Venetoclax and Decitabine for Treatment of Relapsed T-Cell Acute Lymphoblastic Leukemia: A Case Report and Review of Literature. Hematol. Oncol. Stem Cell Ther. 2021; 14: 246–51. DOI: 10.1016/j.hemonc.2019.10.002.Zappone E., Cencini E., Defi na M., et al. Venetoclax in Association with Decitabine as Effective Bridge to Transplant in a Case of Relapsed Early T-Cell Lymphoblastic Leukemia. Clin. Case Rep. 2020; 8: 2000–2. DOI: 10.1002/ccr3.3041.Zappone E., Cencini E., Defina M., et al. Venetoclax in Association with Decitabine as Effective Bridge to Transplant in a Case of Relapsed Early T-Cell Lymphoblastic Leukemia. Clin. Case Rep. 2020; 8: 2000–2. DOI: 10.1002/ccr3.3041.Rosolen A., Perkins S.L., Pinkerton C.R., et al. Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol. 2015; 33(18): 2112–8. DOI: 10.1200/JCO.2014.59.7203.Rosolen A., Perkins S.L., Pinkerton C.R., et al. Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol. 2015; 33(18): 2112–8. DOI: 10.1200/JCO.2014.59.7203.Campana D. Monitoring minimal residual disease in pediatric hematologic malignancies. Clin Adv Hematol Oncol. 2007; 5(11): 876–7, 915.Campana D. Monitoring minimal residual disease in pediatric hematologic malignancies. Clin Adv Hematol Oncol. 2007; 5(11): 876–7, 915.Stark, B., Avigad, S., Luria, D., et al. Bone marrow minimal disseminated disease (MDD) and minimal residual disease (MRD) in childhood T-cell lymphoblastic lymphoma stage III, detected by flow cytometry (FC) and real-time quantitative polymerase chain reaction (RQ-PCR). Pediatr Blood Cancer. 2009; 52(1): 20–5. DOI: 10.1002/pbc.21823.Stark, B., Avigad, S., Luria, D., et al. Bone marrow minimal disseminated disease (MDD) and minimal residual disease (MRD) in childhood T-cell lymphoblastic lymphoma stage III, detected by flow cytometry (FC) and real-time quantitative polymerase chain reaction (RQ-PCR). Pediatr Blood Cancer. 2009; 52(1): 20–5. DOI: 10.1002/pbc.21823.Hayashi R.J., Hermiston M.L., Teachey D., et al. MRD at the End of Induction and EFS in T-cell Lymphoblastic Lymphoma: Children’s Oncology Group Trial AALL1231. Blood. 2024. DOI: 10.1182/blood.2023021184.Hayashi R.J., Hermiston M.L., Teachey D., et al. MRD at the End of Induction and EFS in T-cell Lymphoblastic Lymphoma: Children’s Oncology Group Trial AALL1231. Blood. 2024. DOI: 10.1182/blood.2023021184.Lovisa F., Gallingani I., Varotto E., et al. Prognostic Role of Minimal Disseminated Disease and NOTCH1/FBXW7 Mutational Status in Children with Lymphoblastic Lymphoma: The AIEOP Experience. Diagnostics. 2021; 11(9): 1594. DOI: 10.3390/diagnostics11091594.Lovisa F., Gallingani I., Varotto E., et al. Prognostic Role of Minimal Disseminated Disease and NOTCH1/FBXW7 Mutational Status in Children with Lymphoblastic Lymphoma: The AIEOP Experience. Diagnostics. 2021; 11(9): 1594. DOI: 10.3390/diagnostics11091594.Burkhardt B.,Taj M., Garnier N., et al. Treatment and Outcome Analysis of 639 Relapsed Non-Hodgkin Lymphomas in Children and Adolescents and Resulting Treatment Recommendations. Cancers. 2021; 13(9): 2075. DOI: 10.3390/cancers13092075.Burkhardt B.,Taj M., Garnier N., et al. Treatment and Outcome Analysis of 639 Relapsed Non-Hodgkin Lymphomas in Children and Adolescents and Resulting Treatment Recommendations. Cancers. 2021; 13(9): 2075. DOI: 10.3390/cancers13092075.Burkhardt B., Reiter A., Landmann E., et al. Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: a report from the Berlin-Frankfurt-Muenster group. J Clin Oncol. 2009; 27(20): 3363–9. DOI: 10.1200/JCO.2008.19.3367.Burkhardt B., Reiter A., Landmann E., et al. Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: a report from the Berlin-Frankfurt-Muenster group. J Clin Oncol. 2009; 27(20): 3363–9. DOI: 10.1200/JCO.2008.19.3367.Gross T.G., Hale G.A., He W., et al. Hematopoietic stem cell transplantation for refractory or recurrent non-Hodgkin lymphoma in children and adolescents. Biol Blood Marrow Transplant. 2010; 16(2): 223–30. DOI: 10.1016/j.bbmt.2009.09.021.Gross T.G., Hale G.A., He W., et al. Hematopoietic stem cell transplantation for refractory or recurrent non-Hodgkin lymphoma in children and adolescents. Biol Blood Marrow Transplant. 2010; 16(2): 223–30. DOI: 10.1016/j.bbmt.2009.09.021.Mitsui T., Mori T., Fujita N., et al. Lymphoma Committee, Japanese Pediatric Leukemia/Lymphoma Study Group. Retrospective analysis of relapsed or primary refractory childhood lymphoblastic lymphoma in Japan. Pediatr Blood Cancer. 2009; 52(5): 591–5. DOI: 10.1002/pbc.21941.Mitsui T., Mori T., Fujita N., et al. Lymphoma Committee, Japanese Pediatric Leukemia/Lymphoma Study Group. Retrospective analysis of relapsed or primary refractory childhood lymphoblastic lymphoma in Japan. Pediatr Blood Cancer. 2009; 52(5): 591–5. DOI: 10.1002/pbc.21941.Michaux K., Bergeron C., Gandemer V., et al. SFCE and the EORTC children leukemia group. Relapsed or Refractory Lymphoblastic Lymphoma in Children: Results and Analysis of 23 Patients in the EORTC 58951 and the LMT96 Protocols. Pediatr Blood Cancer. 2016; 63(7): 1214–21. DOI: 10.1002/pbc.25990.Michaux K., Bergeron C., Gandemer V., et al. SFCE and the EORTC children leukemia group. Relapsed or Refractory Lymphoblastic Lymphoma in Children: Results and Analysis of 23 Patients in the EORTC 58951 and the LMT96 Protocols. Pediatr Blood Cancer. 2016; 63(7): 1214–21. DOI: 10.1002/pbc.25990.Jacoby E., Shahani S.A., Shah N.N. Updates on CAR T-cell therapy in B-cell malignancies. Immunol Rev. 2019; 290(1): 39–59. DOI: 10.1111/imr.12774.Jacoby E., Shahani S.A., Shah N.N. Updates on CAR T-cell therapy in B-cell malignancies. Immunol Rev. 2019; 290(1): 39–59. DOI: 10.1111/imr.12774.Raje N., Berdeja J., Lin Y., et al. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2019; 380(18): 1726– 37. DOI: 10.1056/NEJMoa1817226.Raje N., Berdeja J., Lin Y., et al. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2019; 380(18): 1726– 37. DOI: 10.1056/NEJMoa1817226.Sánchez-Martínez D., Baroni M.L., Gutierrez-Agüera F., et al. Fratricideresistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia. Blood. 2019; 133(21): 2291–304. DOI: 10.1182/blood-2018-10-882944.Sánchez-Martínez D., Baroni M.L., Gutierrez-Agüera F., et al. Fratricideresistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia. Blood. 2019; 133(21): 2291–304. DOI: 10.1182/blood-2018-10-882944.Tong C., Zhang Y., Liu Y., et al. Optimized tandem CD19/CD20 CAR-engineered T cells in refractory/relapsed B-cell lymphoma. Blood. 2020; 136(14): 1632–44. DOI: 10.1182/blood.2020005278.Tong C., Zhang Y., Liu Y., et al. Optimized tandem CD19/CD20 CAR-engineered T cells in refractory/relapsed B-cell lymphoma. Blood. 2020; 136(14): 1632–44. DOI: 10.1182/blood.2020005278.Mamonkin M., Rouce R.H., Tashiro H., et al. A T-cell-directed chimeric antigen receptor for the selective treatment of T-cell malignancies. Blood. 2015; 126(8): 983–92. DOI: 10.1182/blood-2015-02-629527.Mamonkin M., Rouce R.H., Tashiro H., et al. A T-cell-directed chimeric antigen receptor for the selective treatment of T-cell malignancies. Blood. 2015; 126(8): 983–92. DOI: 10.1182/blood-2015-02-629527.Maciocia P.M., Wawrzyniecka P.A., Philip B., et al. Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies. Nat Med. 2017; 23(12): 1416–23. DOI: 10.1038/nm.4444.Maciocia P.M., Wawrzyniecka P.A., Philip B., et al. Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies. Nat Med. 2017; 23(12): 1416–23. DOI: 10.1038/nm.4444.Cooper M.L., Choi J., Staser K., et al. An “off-the-shelf” fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies. Leukemia. 2018; 32(9): 1970–83. DOI: 10.1038/s41375-018-0065-5.Cooper M.L., Choi J., Staser K., et al. An “off-the-shelf” fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies. Leukemia. 2018; 32(9): 1970–83. DOI: 10.1038/s41375-018-0065-5.Tang J., Li J., Zhu X., et al. Novel CD7-specific nanobody-based immunotoxins potently enhanced apoptosis of CD7-positive malignant cells. Oncotarget. 2016; 7(23): 34070–83. DOI: 10.18632/oncotarget.8710.Tang J., Li J., Zhu X., et al. Novel CD7-specifi c nanobody-based immunotoxins potently enhanced apoptosis of CD7-positive malignant cells. Oncotarget. 2016; 7(23): 34070–83. DOI: 10.18632/oncotarget.8710.Yu Y., Li J., Zhu X., et al. Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential. Int J Nanomedicine. 2017; 12: 1969–83. DOI: 10.2147/IJN.S127575.Yu Y., Li J., Zhu X., et al. Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential. Int J Nanomedicine. 2017; 12: 1969–83. DOI: 10.2147/IJN.S127575.Zhang M., Chen D., Fu X., et al. Autologous Nanobody-Derived FratricideResistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory Tcell Acute Lymphoblastic Leukemia/Lymphoma. Clin Cancer Res. 2022; 28(13): 2830–843. DOI: 10.1158/1078-0432.CCR-21-4097.Zhang M., Chen D., Fu X., et al. Autologous Nanobody-Derived FratricideResistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory Tcell Acute Lymphoblastic Leukemia/Lymphoma. Clin Cancer Res. 2022; 28(13): 2830–843. DOI: 10.1158/1078-0432.CCR-21-4097.Maciocia P.M., Wawrzyniecka P.A., Philip B., et al. Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies. Nat Med. 2017; 23(12): 1416–23. DOI: 10.1038/nm.4444.Maciocia P.M., Wawrzyniecka P.A., Philip B., et al. Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies. Nat Med. 2017; 23(12): 1416–23. DOI: 10.1038/nm.4444.Feng J., Xu H., Cinquina A., et al. Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells. Stem Cell Rev Rep. 2021; 17(2): 652–61. DOI: 10.1007/s12015-020-10092-9.Feng J., Xu H., Cinquina A., et al. Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells. Stem Cell Rev Rep. 2021; 17(2): 652–61. DOI: 10.1007/s12015-020-10092-9.Xie L., Ma L., Liu S., et al. Chimeric antigen receptor T cells targeting CD7 in a child with high-risk T-cell acute lymphoblastic leukemia. Int Immunopharmacol. 2021; 96: 107731. DOI: 10.1016/j.intimp.2021.107731.Xie L., Ma L., Liu S., et al. Chimeric antigen receptor T cells targeting CD7 in a child with high-risk T-cell acute lymphoblastic leukemia. Int Immunopharmacol. 2021; 96: 107731. DOI: 10.1016/j.intimp.2021.107731.Reinhold U., Abken H., Kukel S., et al. CD7- T cells represent a subset of normal human blood lymphocytes. J Immunol. 1993; 150(5): 2081–9.Reinhold U., Abken H., Kukel S., et al. CD7- T cells represent a subset of normal human blood lymphocytes. J Immunol. 1993; 150(5): 2081–9.Lu P., Liu Y., Yang J., et al. Naturally selected CD7 CAR-T therapy without genetic manipulations for T-ALL/LBL: first-in-human phase 1 clinical trial. Blood. 2022; 140(4): 321–34. DOI: 10.1182/blood.2021014498.Lu P., Liu Y., Yang J., et al. Naturally selected CD7 CAR-T therapy without genetic manipulations for T-ALL/LBL: first-in-human phase 1 clinical trial. Blood. 2022; 140(4): 321–34. DOI: 10.1182/blood.2021014498.

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