Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2023; 22: 53-61
Терапия злокачественных лимфопролиферативных заболеваний у пациентов с первичными иммунодефицитными состояниями с дефектами репарации ДНК
https://doi.org/10.24287/1726-1708-2023-22-1-53-61Аннотация
Синдром Ниймеген (СН) и синдром атаксии-телеангиэктазии (АТ; синдром Луи–Бар) относятся к первичным иммунодефицитным состояниям (ПИДС), которые характеризуются нарушением репарации ДНК и хромосомной нестабильностью, приводящими к предрасположенности к различным онкологическим заболеваниям. В данном ретроспективном исследовании описаны особенности течения и терапии 28 случаев злокачественных новообразований (ЗНО) у 14 пациентов с АТ и у 10 пациентов с СН, наблюдавшихся в ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России с 01.01.2007 по 31.12.2022. Исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева. Среди 14 пациентов с АТ выявлено 16 случаев онкологических заболеваний: 3 случая Т-клеточного острого лимфобластного лейкоза (ОЛЛ), 2 – В-клеточного ОЛЛ, 6 – зрелых В-клеточных неходжкинских лимфом (В-НХЛ), 2 – лимфомы Ходжкина (ЛХ), 1 – NK/T-клеточной лимфомы, 1 – Т-лимфобластной лимфомы, 1 – медуллобластомы. Среди 10 пациентов с СН выявлено всего 12 случаев ЗНО: 6 – диффузной В-клеточной крупноклеточной лимфомы (ДВККЛ), 1 – ЛХ, 2 – периферической Т-клеточной лимфомы, 2 – Т-клеточного пролимфоцитарного лейкоза, 1 – эпителиоидной рабдомиосаркомы. Среди всех ЗНО преобладали зрелые В-НХЛ – 42%, из них чаще всего встречалась ДВККЛ – 91%. Среди всех ПИДС отмечено 4 случая развития второй опухоли: 2 случая у пациентов с АТ, 2 – у пациентов с СН. Диагноз ПИДС до начала терапии ЗНО был заподозрен или подтвержден в 62% случаев у пациентов с АТ, в 100% случаев у пациентов с СН. Терапия проводилась согласно протоколам по нозологическим формам с модификациями доз химиопрепаратов. Среди пациентов с АТ редукция доз химиопрепаратов проводилась в 93% случаев, среди СН – в 80% случаев. Уровень достижения ремиссии был достаточно высоким: пациенты с АТ – 81%, пациенты с СН – 58%. По нашим данным, использование схем терапии с редуцированными дозами химиопрепаратов позволяют получить удовлетворительный профиль токсичности без снижения общей эффективности лечения.
Список литературы
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19. Perez-Vera, P., Gonz alez-del Angel, A., Molina, B., G omez, L., Frías, S., Gatti, R.A., Carnevale, A., 1997. Chromosome instability with bleomycin and x-ray hypersensitivity in a boy with Nijmegen breakage syndrome. Am. J. Med. Genet. 70, 24e27.
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24. Pastorczak, A., Szczepanski, T., Mlynarski, W., & International Berlin-Frankfurt-Munster (I-BFM) ALL host genetic variation working group (2016). Clinical course and therapeutic implications for lymphoid malignancies in Nijmegen breakage syndrome. European journal of medical genetics, 59(3), 126–132. https://doi.org/10.1016/j.ejmg.2016.01.007
Pediatric Hematology/Oncology and Immunopathology. 2023; 22: 53-61
Treatment of lymphoid malignancies in patients with primary immunodeficiencies associated with DNA repair defects
https://doi.org/10.24287/1726-1708-2023-22-1-53-61Abstract
Nijmegen breakage syndrome (NBS) and ataxia-telangiectasia (AT; Louis–Bar syndrome) are primary immunodeficiencies (PID) associated with chromosome instability and DNA repair defects that predispose individuals to an increased risk of various malignancies. In our study, we retrospectively analyzed clinical characteristics and outcomes of 28 cancer cases in 14 patients with AT and 10 patients with NBS who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology between January 2007 and December 2022. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The most common type of malignancy was mature B-cell non-Hodgkin lymphoma (B-NHL) (42%), with diffuse large B-cell lymphoma (DLBCL) accounting for 91% of all B-NHL cases. Other cases included T-cell acute lymphoblastic leukemia (ALL) (n = 3), B-cell ALL (n = 2), Hodgkin lymphoma (n = 3), NK/T-cell lymphoma (n = 1), T-cell lymphoblastic lymphoma (n = 1), peripheral T- cell lymphoma (n = 2), medulloblastoma (n = 1) epithelioid rhabdomyosarcoma (n = 1), T-cell prolymphocytic leukemia (n = 2). A total of 4 patients were diagnosed with second malignancies (2 children with AT and 2 children with NBS. The diagnosis of PID was suspected or confirmed before the initiation of cancer therapy in 62% of AT patients and in 100% of NBS patients. Treatment was given in accordance with standard protocols with chemotherapy dose modifications. A total of 93% of patients with AT and 80% of patients with NBS required dose reduction. The level of response was quite high: 81% of patients with AT and 58% of patients with NBS achieved complete remission. According to our data, the use of reduced-dose chemotherapy regimens helps to achieve an acceptable toxicity profile without reducing the overall effectiveness of treatment.
References
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15. Gladkowska-Dura, M., Dzierzanowska-Fangrat, K., Dura, W. T., van Krieken, J. H., Chrzanowska, K. H., van Dongen, J. J., & Langerak, A. W. (2008). Unique morphological spectrum of lymphomas in Nijmegen breakage syndrome (NBS) patients with high frequency of consecutive lymphoma formation. The Journal of pathology, 216(3), 337–344. https://doi.org/10.1002/path.2418
16. Seidemann, K., Tiemann, M., Henze, G., Sauerbrey, A., Müller, S., & Reiter, A. (1999). Therapy for non-Hodgkin lymphoma in children with primary immunodeficiency: analysis of 19 patients from the BFM trials. Medical and pediatric oncology, 33(6), 536–544.
17. Dembowska-Baginska, B., Perek, D., Brozyna, A., Wakulinska, A., Olczak-Kowalczyk, D., Gladkowska-Dura, M., Grajkowska, W., & Chrzanowska, K. H. (2009). Non-Hodgkin lymphoma (NHL) in children with Nijmegen Breakage syndrome (NBS). Pediatric blood & cancer, 52(2), 186–190.
18. Seidemann, K., Henze, G., Beck, J. D., Sauerbrey, A., Kühl, J., Mann, G., & Reiter, A. (2000). Non-Hodgkin's lymphoma in pediatric patients with chromosomal breakage syndromes (AT and NBS): experience from the BFM trials. Annals of oncology : official journal of the European Society for Medical Oncology, 11 Suppl 1, 141–145.
19. Perez-Vera, P., Gonz alez-del Angel, A., Molina, B., G omez, L., Frías, S., Gatti, R.A., Carnevale, A., 1997. Chromosome instability with bleomycin and x-ray hypersensitivity in a boy with Nijmegen breakage syndrome. Am. J. Med. Genet. 70, 24e27.
20. Kropshofer G,Wehl G, Klein-Franke A, et al. B-cell lymphoma in a girl with ataxia teleangiectasia (A–T) treated with rituximab monotherapy. Pediatr Blood Cancer 2006;46:528–529.
21. Rossi G, Zecca M, Marchi A, et al. Modified chop-chemotherapy plus rituximab for diffuse large b-cell lymphoma complicating ataxia–telangiectasia. Br J Haematol 2003;120:369–371.
22. Shabbat S, Aharoni J, Sarid L, et al. Rituximab as monotherapy and in addition to reduced CHOP in children with primary immunodeficiency and non-Hodgkin lymphoma. Pediatr Blood Cancer 2009;52:664–666.
23. Bienemann K, Burkhardt B, Modlich S, et al: Promising therapy results for lymphoid malignancies in children with chromosomal breakage syndromes (ataxia telangiectasia or Nijmegen-breakage syndrome): A retrospective survey. Br J Haematol 155:468-476, 2011
24. Pastorczak, A., Szczepanski, T., Mlynarski, W., & International Berlin-Frankfurt-Munster (I-BFM) ALL host genetic variation working group (2016). Clinical course and therapeutic implications for lymphoid malignancies in Nijmegen breakage syndrome. European journal of medical genetics, 59(3), 126–132. https://doi.org/10.1016/j.ejmg.2016.01.007
