OncohematologyOncohematologyОнкогематология1818-83462413-4023Publishing House ABV Press89610.17650/1818-8346-2024-19-1-40-50HEMATOLOGIC MALIGNANCIES: TREATMENTЛЕЧЕНИЕ ГЕМОБЛАСТОЗОВThe experience of relapsed Burkitt lymphoma treatment with targeted drugs and autologous/allogeneic stem cell transplantationОпыт лечения рецидивов лимфомы Беркитта с применением таргетных препаратов и аутологичной/аллогенной трансплантации гемопоэтических стволовых клетокhttps://orcid.org/0000-0002-1469-2365ValievT. T.ВалиевТ. Т.
Russian Federation

Timur Teymurazovich Valiev

23 Kashirskoe Shosse, Moscow 115522

Тимур Теймуразович Валиев

115522 Москва, Каширское шоссе, 23

timurvaliev@mail.ruhttps://orcid.org/0000-0002-5803-3863KhachatryanA. A.ХачатрянА. А.
Russian Federation

23 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 23

https://orcid.org/0000-0001-5136-9172GoryachevaS. V.ГорячеваС. В.
Russian Federation

23 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 23

https://orcid.org/0000-0002-3005-2085BatmanovaN. A.БатмановаН. А.
Russian Federation

23 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 23

https://orcid.org/0000-0002-2945-284XKirgizovK. I.КиргизовК. И.
Russian Federation

23 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 23

https://orcid.org/0000-0001-6131-1783VarfolomeevaS. R.ВарфоломееваС. Р.
Russian Federation

23 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 23

Research Institute of Pediatric Oncology and Hematology, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaНИИ детской онкологии и гематологии ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России2701202419140502501202425012024https://oncohematology.abvpress.ru/ongm/article/view/896

The use of high-effective, multicomponent, risk-adopted chemoimmunotherapy schemes in children with Burkitt lymphoma reached advanced long-term progression-free survival over 90 % even for high risk patients. Unfortunately, conventional therapeutic strategy for relapsed/refractory disease is not accepted, and the effectiveness of carboplat‑in- and gemcitabine-containing regimens is unsatisfactory. Clinical experience of rituximab, ibrutinib and nivolumab in combination with polychemotherapy and own clinical case of successful relapsed Burkitt lymphoma treatment with targeted therapy and following autologous and allogeneic hematopoietic stem cell transplantation are presented. Proposed program could achieve a complete remission of Burkitt lymphoma, but short-term after allogeneic hematopoietic stem cell transplantation diagnosed T-cell precursor acute lymphoblastic leukemia became fatal for the patient.

Применение высокоэффективных многокомпонентных риск-адаптированных схем химиоиммунотерапии у детей с лимфомой Беркитта позволило добиться многолетней выживаемости без прогрессирования, превышающей 90 % даже у пациентов группы высокого риска. Единая тактика терапии рецидивирующих/рефрактерных форм заболевания не принята, а результаты использования карбоплатин- и гемцитабинсодержащих схем остаются неудовлетворительными. В статье приводится описание опыта использования ритуксимаба, ибрутиниба, ниволумаба в сочетании с полихимиотерапией и клинического наблюдения успешного лечения рецидивирующего течения лимфомы Беркитта с применением таргетных агентов, аутологичной и аллогенной трансплантации гемопоэтических стволовых клеток. Предложенная тактика терапии позволила получить полную ремиссию лимфомы Беркитта, но развившийся в короткие сроки после аллогенной трансплантации гемопоэтических стволовых клеток Т-линейный острый лимфобластный лейкоз стал фатальным для больного.

Burkitt lymphomahematopoietic stem cell transplantationrelapsesecond-line therapytargeted therapyлимфома Беркиттатрансплантация гемопоэтических стволовых клетокрецидивтерапия 2‑й линиитаргетная терапияBaryakh E.A., Tyurina N.G., Vorobiev V.I. et al. Twelve years of experience in Burkitt’s lymphoma treatment using LB-M-04 protocol. Terapevticheskiy arkhiv = Therapeutic archive 2015;87(7):4–14. (In Russ.).Барях Е.А., Тюрина Н.Г., Воробьев В.И. и др. Двенадцатилетний опыт терапии лимфомы Беркитта по протоколу ЛБ-М-04. Терапевтический архив 2015;87(7):4–14.Woessmann W., Zimmermann M., Meinhardt A. et al. Progressive or relapsed Burkitt lymphoma or leukemia in children and adolescents after BFM-type first-line therapy. Blood 2020;135(14):1124–32. DOI: 10.1182/blood.2019003591Griffin T.C., Weitzman S., Weinstein H. et al. A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in children with recurrent/refractory B-cell (CD20+) nonHodgkin lymphoma and mature B-cell acute lymphoblastic leukemia: A report from the Children’s Oncology Group. Pediatr Blood Cancer 2009;52(2):177–81. DOI: 10.1002/pbc.21753Osumi T., Mori T., Fujita N. et al. Relapsed/refractory pediatric B-cell non-Hodgkin lymphoma treated with rituximab combination therapy: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group. Pediatr Blood Cancer 2016;63(10):1794–9. DOI: 10.1002/pbc.26105Rigaud C., Auperin A., Jourdain A. et al. Outcome of relapse in children and adolescents with B-cell non-Hodgkin lymphoma and mature acute leukemia: a report from the French LMB study. Pediatr Blood Cancer 2019;66(9):e27873. DOI: 10.1002/pbc.27873Philip T., Hartmann O., Pinkerton R. et al. Curability of relapsed childhood B-cell non-Hodgkin’s lymphoma after intensive first line therapy: a report from the Société Française d’Oncologie Pédiatrique. Blood 1993;81(8):2003–6.Atra A., Gerrard M., Hobson R. et al. Outcome of relapsed or refractory childhood B-cell acute lymphoblastic leukaemia and B-cell non-Hodgkin’s lymphoma treated with the UKCCSG 9003/9002 protocols. Br J Haematol 2003;112(4):965–8. DOI: 10.1046/j.1365-2141.2001.02647.xAttarbaschi A., Dworzak M., Steiner M. et al. Outcome of children with primary resistant or relapsed non-Hodgkin lymphoma and mature B-cell leukemia after intensive first-line treatment: a population-based analysis of the Austrian Cooperative Study Group. Pediatr Blood Cancer 2005;44(1):70–6. DOI: 10.1002/pbc.20121Fujita N., Mori T., Mitsui T. et al. Lymphoma Committee of the Japanese Pediatric Leukemia/Lymphoma Study Group. The role of hematopoietic stem cell transplantation with relapsed or primary refractory childhood B-cell non-Hodgkin lymphoma and mature B-cell leukemia: a retrospective analysis of enrolled cases in Japan. Pediatr Blood Cancer 2008;51(2):188–92. DOI: 10.1002/pbc.21585Anoop P., Sankpal S., Stiller C. et al. Outcome of childhood relapsed or refractory mature B-cell non-Hodgkin lymphoma and acute lymphoblastic leukemia. Leuk Lymphoma 2012;53(10): 1882–8. DOI: 10.3109/10428194.2012.677534Kim H., Park E.S., Lee S.H. et al. Clinical outcome of relapsed or refractory Burkitt lymphoma and mature B-cell lymphoblastic leukemia in children and adolescents. Cancer Res Treat 2014;46(4):358–65. DOI: 10.4143/crt.2013.047Burkhardt 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/cancers13092075Zhang Q., Zhu X., Liu B. et al. Case report: sandwich therapy of CAR-T combined with ASCT: sequential CAR-T cell therapy with ASCT after remission with CAR-T therapy caused long-term survival in a patient with relapsed/refractory Burkitt’s lymphoma with TP53 mutations. Front Immunol 2023;14:1127868. DOI: 10.3389/fimmu.2023.1127868Newman A.M., Zaka M., Zhou P. et al. Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma. Leukemia 2022;36(3):781–9. DOI: 10.1038/s41375-021-01444-6Giulino-Roth L., Ricafort R., Kernan N.A. et al. Ten-year followup of pediatric patients with non-Hodgkin lymphoma treated with allogeneic or autologous stem cell transplantation. Pediatr Blood Cancer 2013;60(12):2018–24. DOI: 10.1002/pbc.24722Gardenswartz A., Mehta B., El-Mallawany N. et al. Safety and efficacy of myeloablative conditioning autologous stem cell transplantation, targeted immunotherapy, and reduced intensity conditioning allogeneic stem cell transplantation in children, adolescents, and young adults with relapsed/refractory mature B-cell non-Hodgkin lymphoma [abstract]. Biol Blood Marrow Transplant 2019;25(Suppl):S412.Herrera A.F., Chen L., Khajavian S. et al. Allogeneic stem cell transplantation provides durable remission in patients with primary mediastinal large B cell lymphoma. Biol Blood Marrow Transplant 2019;25(12):2383–7. DOI: 10.1016/j.bbmt.2019.07.041Liu Y., Deng B., Hu B. et al. Sequential different B-cell antigen– targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt lymphoma. Blood Adv 2022;6(3):717–30. DOI: 10.1182/bloodadvances.2021004557Liu Y., Deng B., Hu B. et al. Sequential different B-cell antigen–targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt lymphoma. Blood Adv 2022;6(3):717–30. DOI: 10.1182/bloodadvances.2021004557Moleti M.L., Testi A.M., Foà R. Treatment of relapsed/refractory paediatric aggressive B-cell non-Hodgkin lymphoma. Br J Haematol 2020;189(5):826–43. DOI: 10.1111/bjh.16461Frazer J.K., Li K.J., Galardy P.J. et al. Excellent outcomes in children and adolescents with CNS+ Burkitt lymphoma or other mature B-NHL using only intrathecal and systemic chemoimmunotherapy: results from FAB/LMB96 and COG ANHL01P1. Br J Haematol 2019;185(2):374–7. DOI: 10.1111/bjh.15520Goy A., Ramchandren R., Ghosh N. et al. Ibrutinib plus lenalidomide and rituximab has promising activity in relapsed/ refractory non-germinal center B-cell-like DLBCL. Blood 2019;134(13):1024–36. DOI: 10.1182/blood.2018891598Younes A., Sehn L.H., Johnson P. et al. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol 2019;37(15):1285–95. DOI: 10.1200/JCO.18.02403Bock A.M., Nowakowski G.S., Wang Y. Bispecific antibodies for non-Hodgkin lymphoma treatment. Curr Treat Options Oncol 2022;23(2):155–70. DOI: 10.1007/s11864-021-00925-1Fisher K.E., Ferguson L.S., Coffey A.M. et al. Programmed cell death ligand 1 expression in aggressive pediatric non-Hodgkin lymphomas: frequency, genetic mechanisms, and clinical significance. Haematologica 2022;107(8):1880–90. DOI: 10.3324/haematol.2021.280342Smith S.D., Till B.G., Shadman M.S. et al. Pembrolizumab with R-CHOP in previously untreated diffuse large B-cell lymphoma: potential for biomarker driven therapy. Br J Haematol 2020;189(6):1119–26. DOI: 10.1111/bjh.16494Granai M., Mundo L., Akarca A.U. et al. Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program. Infect Agent Cancer 2020;15:28. DOI: 10.1186/s13027-020-00292-wLiu Y., Zhou X., Wang X. Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities. J Hematol Oncol 2021;14(1):125. DOI: 10.1186/s13045-021-01134-xT.T. Valiev. Burkitt lymphoma in children: 30 year treatment expirience. Pediatriya. Zhurnal im. G.N. Speranskogo = Pediatrics n.a. G.N. Speransky 2020;99(4):35–42. (In Russ.).Валиев Т.Т. Лимфома Беркитта у детей: 30 лет терапии. Педиатрия. Журнал им. Г.Н. Сперанского 2020;99(4):35–41.Utesheva K.I., Valiev T.T., Ignatenko O.A. et al. A clinical case of immune-mediated pneumonitis after nivolumab in a patient with Burkitt lymphoma. Onkogematologiya = Oncohematology 2023;18(1):121–5. (In Russ.). DOI: 10.17650/1818­8346­2023­18­1­121­125Утешева К.И., Валиев Т.Т., Игнатенко О.А. и др. Клинический случай иммуноопосредованного пневмонита после терапии ниволумабом у пациента с лимфомой Беркитта. Онкогематология 2023;18(1):121–5. DOI: 10.17650/1818­8346­2023­18­1­121­125Colton B.S., Hornstein N., Timmerman J. et al. Nivolumab treatment of Burkitt lymphoma: a case report. Ann Intern Med 2021;174(4):567–8. DOI: 10.7326/L20-1090Polaskova K., Merta T., Martincekova A. et al. Comprehensive molecular profiling for relapsed/refractory pediatric Burkitt lymphomas-retrospective analysis of three real-life clinical cases-addressing issues on randomization and customization at the bedside. Front Oncol 2020;9:1531. DOI: 10.3389/fonc.2019.01531Brown A.L., Hahn C.N., Scott H.S. Secondary leukemia in patients with germline transcription factor mutations (RUNX1, GATA2, CEBPA). Blood 2020;136(1):24–35. DOI: 10.1182/blood.2019000937Hertenstein B., Hambach L., Bacigalupo A. et al. Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation. Development of leukemia in donor cells after allogeneic stem cell transplantation – a survey of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica 2005;90(7):969–75.Wiseman D.H. Donor cell leukemia: a review. Biol Blood Marrow Transplant 2011;17(6):771–89. DOI: 10.1016/j.bbmt.2010.10.010