Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children51710.24287/1726-1708-2021-20-2-143-147CLINICAL OBSERVATIONSКЛИНИЧЕСКИЕ НАБЛЮДЕНИЯCNS relapse of B-lymphoblastic lymphoma after allogeneic hematopoietic stem cell transplantation: therapy with donor CD19-specific CAR-T cellsЦНС-рецидив В-лимфобластной лимфомы после аллогенной трансплантации гемопоэтических стволовых клеток: терапия донорскими CD19-специфичными CAR-T-лимфоцитамиMolostovaO. O.МолостоваО. О.
Russian Federation

1 Samory Mashela St., Moscow 117997

117997, Москва, ул. Саморы Машела, 1

https://orcid.org/0000-0003-0520-5630ShelikhovaL. N.ШелиховаЛ. Н.
Russian Federation

Larisa N. Shelikhova, cand. med. sci., Head of the Department of Hematopoietic Stem Cell Transplantation No.1

 1 Samory Mashela St., Moscow 117997

Шелихова Лариса Николаевна, канд. мед. наук, заведующая отделением трансплантации гемопоэтических стволовых клеток №1 

117997, Москва, ул. Саморы Машела, 1

lnik1976@mail.ruPershinD. E.ПершинД. Е.
Russian Federation

1 Samory Mashela St., Moscow 117997

117997, Москва, ул. Саморы Машела, 1

PopovA. M.ПоповА. М.
Russian Federation

1 Samory Mashela St., Moscow 117997

117997, Москва, ул. Саморы Машела, 1

DubrovinaM. E.ДубровинаМ. Э.
Russian Federation

1 Samory Mashela St., Moscow 117997

117997, Москва, ул. Саморы Машела, 1

KlimentovaM. A.КлиментоваМ. А.
Russian Federation

1 Samory Mashela St., Moscow 117997

117997, Москва, ул. Саморы Машела, 1

https://orcid.org/0000-0002-0016-6698MaschanA. A.МасчанА. А.
Russian Federation

1 Samory Mashela St., Moscow 117997

117997, Москва, ул. Саморы Машела, 1

https://orcid.org/0000-0003-1735-0093MaschanM. A.МасчанМ. А.
Russian Federation

1 Samory Mashela St., Moscow 117997

117997, Москва, ул. Саморы Машела, 1

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России220520212021431472205202122052021Copyright ©; 2021, «D. Rogachev NMRCPHOI»Copyright ©; 2021, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2021«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/517

Presently, there is no consensus on the best treatment for relapsed B-cell acute lymphoblastic leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in patients with extramedullary lesions. There are certain anti-tumor drugs that can be used in case of relapse after allo-HSCT, however, prospective randomized studies directly comparing different chemotherapy and immunotherapy approaches are generally lacking. Retrospective studies exploring therapy for relapsed disease are difficult to compare due to the inhomogeneity of patient populations and the diversity of treatment approaches. In such situations, the treatment choice is influenced by the characteristics of the tumor population, particularly, its immunophenotype, available drugs, and the experience of a healthcare facility and physicians. This clinical case report describes the process of treating a patient with B-lymphoblastic lymphoma and shows the possibility of using donor CD19-specific CAR-T cells as a treatment for isolated CNS relapse after allo-HSCT. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.

На сегодняшний день нет единого мнения относительно оптимальной тактики лечения рецидивов В-линейного острого лимфобластного лейкоза/лимфомы после аллогенной трансплантации гемопоэтических стволовых клеток (алло-ТГСК), в особенности при наличии экстрамедуллярных очагов поражения. Существует определенный набор противоопухолевых препаратов, которые можно применять в случае рецидива после алло-ТГСК, однако проспективные рандомизированные исследования, которые напрямую бы сравнивали различные подходы к химиотерапии и иммунотерапии, практически отсутствуют. Ретроспективные исследования терапии рецидивов трудно сравнивать из-за неоднородности популяций пациентов и терапевтических подходов. В таких ситуациях на выбор терапии влияют характеристики опухолевой популяции, в частности ее иммунофенотип, доступные препараты, а также опыт медицинского учреждения и врачей. Представленный клинический случай демонстрирует процесс лечения пациента с В-лимфобластной лимфомой и возможность применения донорских CD-19-специфичных CAR-T-лимфоцитов в качестве терапии изолированного ЦНС-рецидива после алло-ТГСК. Родители пациента дали согласие на использование информации, в том числе фотографий ребенка, в научных исследованиях и публикациях.

allogeneic hematopoietic stem cell transplantationrelapseB-lymphoblastic lymphomaCAR-T cellsаллогенная трансплантация гемопоэтических стволовых клетокрецидивВ-лимфобластная лимфомаCAR-T-лимфоциты1. Merli P., Algeri M., Del Bufalo F., Locatelli F. Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoblastic Leukemia. Curr Hematol Malig Rep 2019; 14 (2): 94–105. DOI: 10.1007/s11899-019-00502-2Merli P., Algeri M., Del Bufalo F., Locatelli F. Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoblastic Leukemia. Curr Hematol Malig Rep 2019; 14 (2): 94–105. DOI: 10.1007/s11899-019-00502-22. Giebel S., Boumendil A., Labopin M., Seesaghur A., Baron F., Ciceri F., et al. Trends in the use of hematopoietic stem cell transplantation for adults with acute lymphoblastic leukemia in Europe: a report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Ann Hematol 2019; 98 (10): 2389–98. DOI: 10.1007/s00277-019-03771-2Giebel S., Boumendil A., Labopin M., Seesaghur A., Baron F., Ciceri F., et al. Trends in the use of hematopoietic stem cell transplantation for adults with acute lymphoblastic leukemia in Europe: a report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Ann Hematol 2019; 98 (10): 2389–98. DOI: 10.1007/s00277-019-03771-23. Yaniv I., Krauss A.C., Beohou E., Dalissier A., Corbacioglu S., Zecca M., et al. Second Hematopoietic Stem Cell Transplantation for Post-Transplantation Relapsed Acute Leukemia in Children: A Retrospective EBMT-PDWP StudyBiol Blood Marrow Transplant 2018; 24 (8): 1629–42. DOI: 10.1016/j.bbmt.2018.03.002Yaniv I., Krauss A.C., Beohou E., Dalissier A., Corbacioglu S., Zecca M., et al. Second Hematopoietic Stem Cell Transplantation for Post-Transplantation Relapsed Acute Leukemia in Children: A Retrospective EBMT-PDWP StudyBiol Blood Marrow Transplant 2018; 24 (8): 1629–42. DOI: 10.1016/j.bbmt.2018.03.0024. Maude S.L., Laetsch T.W., Buechner J., Rives S., Boyer M., Bittencourt H., et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med 2018; 378 (5): 439–48.Maude S.L., Laetsch T.W., Buechner J., Rives S., Boyer M., Bittencourt H., et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med 2018; 378 (5): 439–48.5. Lee D.W., Kochenderfer J.N., Stetler-Stevenson M., Cui Y.K., Delbrook C., Feldman S.A., et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 2015; 385 (9967): 517–28.Lee D.W., Kochenderfer J.N., Stetler-Stevenson M., Cui Y.K., Delbrook C., Feldman S.A., et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 2015; 385 (9967): 517–28.6. Smith M., Zakrzewski J., James S., Sadelain M. Posttransplant chimeric antigen receptor therapy. Blood 2018; 131 (10): 1045–52. DOI: 10.1182/blood-2017-08-752121Smith M., Zakrzewski J., James S., Sadelain M. Posttransplant chimeric antigen receptor therapy. Blood 2018; 131 (10): 1045–52. DOI: 10.1182/blood-2017-08-7521217. Chen Y., Cheng Y., Suo P., Yan C., Wang Y., Chen Y., et al. Donor-derived CD19-targeted T cell infusion induces minimal residual disease-negative remission in relapsed B-cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation. Br J Haematol 2017; 179 (4): 598–605. DOI: 10.1111/bjh.14923. Epub 2017 Oct 26. PMID: 29076142.Chen Y., Cheng Y., Suo P., Yan C., Wang Y., Chen Y., et al. Donor-derived CD19-targeted T cell infusion induces minimal residual disease-negative remission in relapsed B-cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation. Br J Haematol 2017; 179 (4): 598–605. DOI: 10.1111/bjh.14923. Epub 2017 Oct 26. PMID: 29076142.8. Yang Y., Jacoby E., Fry T.J. Challenges and opportunities of allogeneic donor-derived CAR T cells. Curr Opin Hematol 2015; 22 (6): 509–15. DOI: 10.1097/MOH.0000000000000181Yang Y., Jacoby E., Fry T.J. Challenges and opportunities of allogeneic donor-derived CAR T cells. Curr Opin Hematol 2015; 22 (6): 509–15. DOI: 10.1097/MOH.00000000000001819. Deol A., Lum L.G. Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited. Cancer Treat Rev 2010; 36 (7): 528–38. DOI: 10.1016/j.ctrv.2010.03.004Deol A., Lum L.G. Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited. Cancer Treat Rev 2010; 36 (7): 528–38. DOI: 10.1016/j.ctrv.2010.03.00410. Talleur A.C., Li Y., Akel S., Sharma A., Qudeimat A., Srinivasan А., et al. Haploidentical CD45RA-Negative Donor LymphocyteI nfusions Are Feasible, Safe and Associated with Clinical Benefit. Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis,TN;2Human Applications Lab, St. Jude Children's Research Hospital, Memphis, TN. DOI: 10.1016/j.bbmt.2019.12.435Talleur A.C., Li Y., Akel S., Sharma A., Qudeimat A., Srinivasan А., et al. Haploidentical CD45RA-Negative Donor LymphocyteI nfusions Are Feasible, Safe and Associated with Clinical Benefit. Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis,TN;2Human Applications Lab, St. Jude Children's Research Hospital, Memphis, TN. DOI: 10.1016/j.bbmt.2019.12.43511. He X., Xiao X., Li Q., Jiang Y., Cao Y., Sun R., et al. Anti-CD19 CAR-T as a feasible and safe treatment against central nervous system leukemia after intrathecal chemotherapy in adults with relapsed or refractory B-ALL. Leukemia 2019; 33: 2102–4. DOI: 10.1038/s41375-019-0437-5He X., Xiao X., Li Q., Jiang Y., Cao Y., Sun R., et al. Anti-CD19 CAR-T as a feasible and safe treatment against central nervous system leukemia after intrathecal chemotherapy in adults with relapsed or refractory B-ALL. Leukemia 2019; 33: 2102–4. DOI: 10.1038/s41375-019-0437-512. Zhang C., Wang X.Q., Zhang R.L., Liu F., Wang Y., Yan Z.-L., et al. Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant. Leukemia 2020. DOI: 10.1038/s41375-020-01056-6Zhang C., Wang X.Q., Zhang R.L., Liu F., Wang Y., Yan Z.-L., et al. Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant. Leukemia 2020. DOI: 10.1038/s41375-020-01056-6