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Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2020; 19: 84-89

Особенности течения рецидивов и рефрактерных форм Т-лимфобластной лимфомы у детей

Абашидзе З. А., Дьяконова Ю. Ю., Мякова Н. В.

https://doi.org/10.24287/1726-1708-2020-19-3-84-89

Аннотация

Лимфобластная лимфома (ЛБЛ) является быстро прогрессирующим злокачественным заболеванием из предшественников Т- и В-клеток. На долю лимфом из Т-клеток-предшественников (Т-ЛБЛ) приходится до 80% всех ЛБЛ. Несмотря на достаточно редкую встречаемость Т-ЛБЛ, рецидивирующее и рефрактерное течение данного заболевания представляет собой актуальную проблему. Программы терапии рецидивов и рефрактерных форм Т-ЛБЛ в настоящее время продолжают активно разрабатываться. Определяются роль и место таргетных препаратов в мультимодальной стратегии лечения рецидивов Т-ЛБЛ. Дальнейшие фундаментальные исследования направлены на преодоление лекарственной резистентности, изучение молекулярногенетических механизмов, сигнальных путей опухолевой клетки, что позволит улучшить результаты лечения и выживаемость. В статье на примере клинического случая рассмотрены особенности течения рецидивов и рефрактерных форм Т-ЛБЛ у детей, а также возможные методы терапии. Родители дали согласие на использование информации, в том числе фотографий ребенка, в научных исследованиях и публикациях.
Список литературы

1. Burkhardt B., Reiter A., Landmann E., Lang P., Lassay L., Dickerhoff R., 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

2. Румянцев А.Г., Масчан А.А., Жуковская Е.В. Федеральные клинические рекомендации. Детская гематология. М.: ГЭОТАР-Медиа; 2015.

3. Burkhardt B., Mueller S., Khanam T., Perkins S.L. Current status and future directions of T-lymphoblastic lymphoma in children and adolescents. Br J Haematol 2016; 173 (4): 545–59. DOI: 10.1111/bjh.14017

4. El-Mallawany N.K., Frazer J.K., Van Vlierberghe P., Ferrando A. A., Perkins S., Lim M., et al. Pediatric T-and NK-cell lymphomas: New biologic insights and treatment strategies. Blood Cancer J 2012; 2(4): е65. DOI: 10.1038/bcj.2012.8

5. T-lymphoblastic lymphoma. World Health Organization (WHO), 2017.

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7. Kobrinsky N.L., Sposto R., Shah N.R., Anderson JR, De Laat C, Morse M., et al. Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912. J Clin Oncol 2001; 19(9): 2390–6.

8. Michaux K., Bergeron C., Gandemer V., Mechinaud F., Uyttebroeck A., Bertrand Y.; 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

9. Callens C., Baleydier F., Lengline E., Ben Abdelali R., Petit A., Villarese P., 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

10. Bonn B.R., Rohde M., Zimmermann M., Krieger D., Oschlies I., Niggli F., et al. Incidence and prognostic relevance of genetic variations in T‐cell lymphoblastic lymphoma in childhood and adolescence. Blood 2013; 121(16): 3153–60.

11. Balbach S.T., Makarova O., Bonn B.R., Zimmermann M., Rohde M., Oschlies I. et al. Proposal of a genetic classifier for risk group stratification in pediatric T‐cell lymphoblastic lymphoma reveals differences from adult T‐cell lymphoblastic leukemia. Leukemia 2016; 30 (4): 970-3. DOI: 10.1038/leu.2015.203.

12. Kobrinsky N.L., Sposto R., Shah N.R., Anderson J.R., DeLaat C., Morse M. et al. Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912. J Clin Oncol 2001; 19(9):2390–6.

13. Harris R.E., Termuhlen A.M., Smith L.M. Lynch J., Henry M.M., Perkins S.L., et al. Autologous peripheral blood stem cell transplantation in children with refractory or relapsed lymphoma: results of Children,s Oncology Group Study A5962. Biol Blood Marrow Transplant 2011; 17(2): 249– 58. DOI: 10.1016/j.bbmt.2010.07.002

14. Gross T.G., Hale G.A., He W., Camitta B.M., Sanders J.E., Cairo M.S. 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.

15. Dunsmore K.P., Devidas M., Linda S.B., Borowitz M.J., Winick N., Hunger S.P., et al. Pilot study of nelarabine in combination with intensive chemotherapy in highrisk T-cell acute lymphoblastic leukemia: a report from the Children’s Oncology Group. J Clin Oncol 2012; 30(22): 2753–9. DOI: 10.1200/JCO.2011.40.8724

16. Валиев Т.Т. Клиническая характеристика и результаты терапии рецидивов/ рефрактерных форм неходжкинских лимфом у детей: обзор литературы и анализ собственных данных. Онкогематология 2018; 13(2): 21–31. DOI: 10.17650/1818-8346-2018-13-2-21-31

17. Cooper T.M., Razzouk B.I., Gerbing R., Alonzo T.A., Adlard K., Raetz E., et al. Phase I/II trial of clofarabine and cytarabine in children with relapsed/refractory acute lymphoblastic leukemia (AAML0523): a report from the Children’s Oncology Group. Pediatr Blood Cancer 2013; 60(7): 1141–7. DOI: 10.1002/pbc.24398

18. Dick L.R., Fleming P.E. Building on bortezomib: second-generation proteasome inhibitors as anticancer therapy. Drug Discov Today 2010; 15 (5–6): 243–9. DOI: 10.1016/j.drudis. 2010.01.008

19. Schmidt E., Burkhardt B. Lymphoblastic lymphoma in childhood and adolescence. Pediatr Hematol Oncol 2013; 30(6): 484– 508. DOI: 10.3109/08880018.2013.789574

Pediatric Hematology/Oncology and Immunopathology. 2020; 19: 84-89

Features of relapses and refractory forms of T-lymphoblastic lymphoma in children

Abashidze Z. A., Dyakonova U. U., Myakova N. V.

https://doi.org/10.24287/1726-1708-2020-19-3-84-89

Abstract

Lymphoblastic lymphoma (LBL) is a rapidly progressive, malignant disease from T and B progenitor cells. Lymphomas from T cell precursors (T-LBL) account for up to 80% of all LBLs. Despite the rather rare occurrence of T-LBL, the relapsing and refractory course of this disease is an actual problem. Programs for the treatment of relapses and refractory forms of T-LBL are currently being actively developing. The role and place of targeted drugs in the multimodal T-LBL relapse strategy is determined. Further fundamental research is aimed at overcoming drug resistance, studying the molecular genetic mechanisms, tumor cell signaling pathways, which will improve treatment outcomes and survival. Based on clinical case the authors will be considered clinical features of relapses and refractory form of T-LBL and possible methods of treatment. Parents gave their consent to use information about the child, including fotos, in the article.
References

1. Burkhardt B., Reiter A., Landmann E., Lang P., Lassay L., Dickerhoff R., 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

2. Rumyantsev A.G., Maschan A.A., Zhukovskaya E.V. Federal'nye klinicheskie rekomendatsii. Detskaya gematologiya. M.: GEOTAR-Media; 2015.

3. Burkhardt B., Mueller S., Khanam T., Perkins S.L. Current status and future directions of T-lymphoblastic lymphoma in children and adolescents. Br J Haematol 2016; 173 (4): 545–59. DOI: 10.1111/bjh.14017

4. El-Mallawany N.K., Frazer J.K., Van Vlierberghe P., Ferrando A. A., Perkins S., Lim M., et al. Pediatric T-and NK-cell lymphomas: New biologic insights and treatment strategies. Blood Cancer J 2012; 2(4): e65. DOI: 10.1038/bcj.2012.8

5. T-lymphoblastic lymphoma. World Health Organization (WHO), 2017.

6. Kobayashi R., Takimoto T., Nakazawa A., Fujita N., Akazai A., Yamato K., et al. Inferior outcomes of stage III T lymphoblastic lymphoma relative to stage IV lymphoma and T‐acute lymphoblastic leukemia: long‐term comparison of outcomes in the JACLS NHL T‐98 and ALL T‐97 protocols. Int J Hematol 2014; 99 (6): 743–9. DOI: 10.1007/s12185-014-1585-z

7. Kobrinsky N.L., Sposto R., Shah N.R., Anderson JR, De Laat C, Morse M., et al. Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912. J Clin Oncol 2001; 19(9): 2390–6.

8. Michaux K., Bergeron C., Gandemer V., Mechinaud F., Uyttebroeck A., Bertrand Y.; 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

9. Callens C., Baleydier F., Lengline E., Ben Abdelali R., Petit A., Villarese P., 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

10. Bonn B.R., Rohde M., Zimmermann M., Krieger D., Oschlies I., Niggli F., et al. Incidence and prognostic relevance of genetic variations in T‐cell lymphoblastic lymphoma in childhood and adolescence. Blood 2013; 121(16): 3153–60.

11. Balbach S.T., Makarova O., Bonn B.R., Zimmermann M., Rohde M., Oschlies I. et al. Proposal of a genetic classifier for risk group stratification in pediatric T‐cell lymphoblastic lymphoma reveals differences from adult T‐cell lymphoblastic leukemia. Leukemia 2016; 30 (4): 970-3. DOI: 10.1038/leu.2015.203.

12. Kobrinsky N.L., Sposto R., Shah N.R., Anderson J.R., DeLaat C., Morse M. et al. Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912. J Clin Oncol 2001; 19(9):2390–6.

13. Harris R.E., Termuhlen A.M., Smith L.M. Lynch J., Henry M.M., Perkins S.L., et al. Autologous peripheral blood stem cell transplantation in children with refractory or relapsed lymphoma: results of Children,s Oncology Group Study A5962. Biol Blood Marrow Transplant 2011; 17(2): 249– 58. DOI: 10.1016/j.bbmt.2010.07.002

14. Gross T.G., Hale G.A., He W., Camitta B.M., Sanders J.E., Cairo M.S. 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.

15. Dunsmore K.P., Devidas M., Linda S.B., Borowitz M.J., Winick N., Hunger S.P., et al. Pilot study of nelarabine in combination with intensive chemotherapy in highrisk T-cell acute lymphoblastic leukemia: a report from the Children’s Oncology Group. J Clin Oncol 2012; 30(22): 2753–9. DOI: 10.1200/JCO.2011.40.8724

16. Valiev T.T. Klinicheskaya kharakteristika i rezul'taty terapii retsidivov/ refrakternykh form nekhodzhkinskikh limfom u detei: obzor literatury i analiz sobstvennykh dannykh. Onkogematologiya 2018; 13(2): 21–31. DOI: 10.17650/1818-8346-2018-13-2-21-31

17. Cooper T.M., Razzouk B.I., Gerbing R., Alonzo T.A., Adlard K., Raetz E., et al. Phase I/II trial of clofarabine and cytarabine in children with relapsed/refractory acute lymphoblastic leukemia (AAML0523): a report from the Children’s Oncology Group. Pediatr Blood Cancer 2013; 60(7): 1141–7. DOI: 10.1002/pbc.24398

18. Dick L.R., Fleming P.E. Building on bortezomib: second-generation proteasome inhibitors as anticancer therapy. Drug Discov Today 2010; 15 (5–6): 243–9. DOI: 10.1016/j.drudis. 2010.01.008

19. Schmidt E., Burkhardt B. Lymphoblastic lymphoma in childhood and adolescence. Pediatr Hematol Oncol 2013; 30(6): 484– 508. DOI: 10.3109/08880018.2013.789574