Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2024; 23: 51-58
Ранние результаты применения протокола NB-HR-2018 у пациентов с нейробластомой группы высокого риска в Республике Беларусь
https://doi.org/10.24287/1726-1708-2024-23-3-51-58Аннотация
Разработка новых критериев для оптимизации терапии нейробластомы группы высокого риска и внедрение новых походов к ее лечению являются актуальной проблемой современной детской онкологии. Цель исследования: разработка и внедрение новых критериев высокой и ультравысокой группы риска, внедрение использования тандемной аутологичной трансплантации гемопоэтических стволовых клеток (ТГСК) в качестве терапии консолидации для пациентов с нейробластомой группы высокого риска, оценка переносимости данного подхода к терапии. Настоящее исследование одобрено независимым этическим комитетом и утверждено решением ученого совета ГУ «Республиканский научно-практический центр детской онкологии, гематологии и иммунологии» (Республика Беларусь). В 2018 г. в Центре детской онкологии, гематологии и иммунологии (Республика Беларусь) был разработан и внедрен протокол NB-HR-2018 с определением новых критериев для лечения пациентов с нейробластомой группы высокого риска. Лечение по новому протоколу получили 23 пациента, 20 из них была выполнена аутологичная ТГСК. Группу сравнения составили 56 пациентов группы высокого риска, получавших терапию по протоколу NB 2004. Применение данного метода достоверно снижает количество рецидивов/частоту прогрессии основного заболевания (р = 0,047) и в группе с тандемной ТГСК имеется тенденция к улучшению бессобытийной выживаемости (56 ± 12% vs 36 ± 6%; р = 0,445). Использование новых критериев для группы высокого риска и новых подходов к терапии (тандемная аутологичная ТГСК) является целесообразным, так как достоверно снижает частоту рецидивов заболевания и удовлетворительно переносится.
Список литературы
1. Matthay K.K., Maris J.M., Schleiermacher G., Nakagawara A., Mackall C.L., Diller L., et al. Neuroblastoma. Nat Rev Dis Primers 2016; 2: 16078. DOI: 10.1038/nrdp.2016.78
2. Pinto N.R., Applebaum M.A., Volchenboum S.L., Matthay K.K., London W.B., Ambros P. F., et al. Advances in risk classification and treatment strategies for neuroblastoma. J Clin Oncol 2015; 33 (27): 3008–17. DOI: 10.1200/ JCO.2014.59.4648
3. Пролесковская И.В., Быданов О.И., Конопля Н.Е. Эпидемиология нейробластомы у детей в Республике Беларусь. Российский журнал детской гематологии и онкологии 2021; 8 (1): 35–42. DOI: 10.21682/2311-1267-2021-8-1-35-42
4. Berthold F., Ernst A., Hero B., Klingebiel T., Kremens B., Schilling F.H., et al. Long-term outcomes of the GPOH NB97 trial for children with high-risk neuroblastoma comparing high-dose chemotherapy with autologous stem cell transplantation and oral chemotherapy as consolidation. Br J Cancer 2018; 119 (3): 282–90. DOI: 10.1038/s41416-018-0169-8
5. Пролесковская И.В., Конопля Н.Е. Результаты лечения нейробластомы группы высокого риска у детей в Республике Беларусь. Гематология. Трансфузиология. Восточная Европа 2022; 8 (4): 389–98.
6. Praliaskouskaya I., Kustanovich A., Movchan L., Vashkevich E., Budanov A., Aleinikova O. Value of the MMD and MRD in Patients with Neuroblastoma. Advances in Neuroblastoma Research. Anr Congress, 13th–16th May 2014, Cologne, Germany. Abstracts, Pot. 119. P. 23.
7. Praliaskouskaya I., Pakhomava I., Romantsova A., Budanov O., Aleinikova O. Prognostic value of minimal residual disease in high-risk neuroblastoma group: protocol NB 2004m, end of induction. ANR2018, San Francisco, May 9th–12th, 2018. Abstract Book ANR 2018. P. 3.
8. Cohen L.E., Gordon J.H., Popovsky E.Y., Gunawardene S., Duffey-Lind E., Lehmann L.E., Diller L.R. Late effects in children treated with intensive multimodal therapy for high-risk neuroblastoma: high incidence of endocrine and growth problems. Bone Marrow Transplant 2014; 49 (4): 502–8. DOI: 10.1038/bmt.2013.218
9. Yu A.L., Gilman A.L., Ozkaynak M.F., London W.B., Kreissman S.G., Chen H.X., et al. Anti-GD2 antibody ith GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010; 363 (14): 1324–34. DOI: 10.1056/NEJMoa0911123
10. Ladenstein R., Potschger U., Pearson A.D.J., Brock P., Luksch R., Castel V., et al. Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): An international, randomized, multi-arm, open-label, phase 3 trial. Lancet Oncol 2017; 18: 500–14. DOI: 10.1016/S1470-2045(17)30070-0
11. Park J.R., Kreissman S.G., London W.B., Naranjo A., Lerner Cohn S., Hogarty M.D., et al. A phase III randomized clinical trial (RCT) of tandem myeloablative autologous stem cell transplant (ASCT) using peripheral blood stem cell (PBSC) as consolidation therapy for highrisk neuroblastoma (HR-NB): A Children's Oncology Group (COG) study. J Clin Oncol 2016; 34 (suppl; abstr. LBA3).
12. Park J.R., Kreissman S.G., London W.B., Naranjo A., Lerner Cohn S., Hogarty M.D., et al. Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma A Randomized Clinical Trial. JAMA 2019; 322 (8): 746–55. DOI: 10.1001/jama.2019.11642
13. Pasqualini C., Dufour C., Goma G., Raquin1M.-A., Lapierre V., Valteau-Couanet D. Tandem high-dose chemotherapy with thiotepa and busulfan–melphalan and autologous stem cell transplantation in very high-risk neuroblastoma patients. Bone Marrow Transplant 2016; 51:227–31.
14. Matthay K.K., Villablanca J.G., Seeger R.C., Stram D.O., Harris R.E., Ramsay N.K., et al.; Children’s Cancer Group. Treatment of highrisk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. N Engl J Med 1999; 341 (16): 1165–73. DOI: 10.1056/NEJM199910143411601
15. Pritchard J., Cotterill S.J., Germond S.M., Imeson J., de Kraker J., Jones D.R. High dose melphalan in the treatment of advanced neuroblastoma: results of a randomized trial (ENSG-1) by the European Neuroblastoma Study Group. Pediatr Blood Cancer 2005; 44 (4): 348–57. DOI: 10.1002/pbc.20219
16. Gurney J.G., Tersak J.M., Ness K.K., Landier W., Matthay K.K., Schmidt M.L. Children’s Oncology Group. Hearing loss, quality of life, and academic problems in longterm neuroblastoma survivors: a report from the Children’s Oncology Group. Pediatrics 2007; 120 (5): e1229–36. DOI: 10.1542/peds.2007-0178
17. Moreno L., Vaidya S.J., Pinkerton C.R., Ross Pinkerto C., Lewis I.J., Imeson J., et al.; European Neuroblastoma Study Group; Children’s Cancer and Leukaemia Group (CCLG) (formerly UKCCSG). Long-term follow-up of children with high-risk neuroblastoma: the ENSG5 trial experience. Pediatr Blood Cancer 2013; 60 (7): 1135–40. DOI: 10.1002/pbc.24452
Pediatric Hematology/Oncology and Immunopathology. 2024; 23: 51-58
Early results of treatment in accordance with the NB-HR-2018 protocol in patients with high-risk neuroblastoma in the Republic of Belarus
https://doi.org/10.24287/1726-1708-2024-23-3-51-58Abstract
The development of new criteria for high-risk neuroblastoma treatment optimization and the introduction of new approaches to its management are a pressing problem in modern pediatric oncology. In this study, we aimed to develop and implement new high-risk and ultra-high-risk criteria, introduce tandem autologous hematopoietic stem cell transplantation (HSCT) as consolidation therapy for high-risk neuroblastoma patients as well as to assess patient tolerability of this treatment. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. In 2018, a new protocol called NB-HR-2018 was developed and implemented at the Center for Pediatric Oncology, Hematology, and Immunology (Belarus) that included new criteria defining high-risk groups. Twenty-three patients were treated according to the new protocol, with 20 of them receiving autologous HSCT. The comparison group included 56 high-risk patients who had undergone treatment in accordance with the NB 2004 protocol. Tandem autoHSCT significantly reduces the rates of underlying disease relapse/progression (p = 0.047) and demonstrates better event-free survival rates (56 ± 12% vs 36 ± 6%; р = 0.445). The use of the new high-risk criteria and the new treatment method (tandem autologous HSCT) is concluded to be a reasonable approach since it significantly reduces disease relapse rates and is well tolerated by the patients.
References
1. Matthay K.K., Maris J.M., Schleiermacher G., Nakagawara A., Mackall C.L., Diller L., et al. Neuroblastoma. Nat Rev Dis Primers 2016; 2: 16078. DOI: 10.1038/nrdp.2016.78
2. Pinto N.R., Applebaum M.A., Volchenboum S.L., Matthay K.K., London W.B., Ambros P. F., et al. Advances in risk classification and treatment strategies for neuroblastoma. J Clin Oncol 2015; 33 (27): 3008–17. DOI: 10.1200/ JCO.2014.59.4648
3. Proleskovskaya I.V., Bydanov O.I., Konoplya N.E. Epidemiologiya neiroblastomy u detei v Respublike Belarus'. Rossiiskii zhurnal detskoi gematologii i onkologii 2021; 8 (1): 35–42. DOI: 10.21682/2311-1267-2021-8-1-35-42
4. Berthold F., Ernst A., Hero B., Klingebiel T., Kremens B., Schilling F.H., et al. Long-term outcomes of the GPOH NB97 trial for children with high-risk neuroblastoma comparing high-dose chemotherapy with autologous stem cell transplantation and oral chemotherapy as consolidation. Br J Cancer 2018; 119 (3): 282–90. DOI: 10.1038/s41416-018-0169-8
5. Proleskovskaya I.V., Konoplya N.E. Rezul'taty lecheniya neiroblastomy gruppy vysokogo riska u detei v Respublike Belarus'. Gematologiya. Transfuziologiya. Vostochnaya Evropa 2022; 8 (4): 389–98.
6. Praliaskouskaya I., Kustanovich A., Movchan L., Vashkevich E., Budanov A., Aleinikova O. Value of the MMD and MRD in Patients with Neuroblastoma. Advances in Neuroblastoma Research. Anr Congress, 13th–16th May 2014, Cologne, Germany. Abstracts, Pot. 119. P. 23.
7. Praliaskouskaya I., Pakhomava I., Romantsova A., Budanov O., Aleinikova O. Prognostic value of minimal residual disease in high-risk neuroblastoma group: protocol NB 2004m, end of induction. ANR2018, San Francisco, May 9th–12th, 2018. Abstract Book ANR 2018. P. 3.
8. Cohen L.E., Gordon J.H., Popovsky E.Y., Gunawardene S., Duffey-Lind E., Lehmann L.E., Diller L.R. Late effects in children treated with intensive multimodal therapy for high-risk neuroblastoma: high incidence of endocrine and growth problems. Bone Marrow Transplant 2014; 49 (4): 502–8. DOI: 10.1038/bmt.2013.218
9. Yu A.L., Gilman A.L., Ozkaynak M.F., London W.B., Kreissman S.G., Chen H.X., et al. Anti-GD2 antibody ith GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010; 363 (14): 1324–34. DOI: 10.1056/NEJMoa0911123
10. Ladenstein R., Potschger U., Pearson A.D.J., Brock P., Luksch R., Castel V., et al. Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): An international, randomized, multi-arm, open-label, phase 3 trial. Lancet Oncol 2017; 18: 500–14. DOI: 10.1016/S1470-2045(17)30070-0
11. Park J.R., Kreissman S.G., London W.B., Naranjo A., Lerner Cohn S., Hogarty M.D., et al. A phase III randomized clinical trial (RCT) of tandem myeloablative autologous stem cell transplant (ASCT) using peripheral blood stem cell (PBSC) as consolidation therapy for highrisk neuroblastoma (HR-NB): A Children's Oncology Group (COG) study. J Clin Oncol 2016; 34 (suppl; abstr. LBA3).
12. Park J.R., Kreissman S.G., London W.B., Naranjo A., Lerner Cohn S., Hogarty M.D., et al. Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma A Randomized Clinical Trial. JAMA 2019; 322 (8): 746–55. DOI: 10.1001/jama.2019.11642
13. Pasqualini C., Dufour C., Goma G., Raquin1M.-A., Lapierre V., Valteau-Couanet D. Tandem high-dose chemotherapy with thiotepa and busulfan–melphalan and autologous stem cell transplantation in very high-risk neuroblastoma patients. Bone Marrow Transplant 2016; 51:227–31.
14. Matthay K.K., Villablanca J.G., Seeger R.C., Stram D.O., Harris R.E., Ramsay N.K., et al.; Children’s Cancer Group. Treatment of highrisk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. N Engl J Med 1999; 341 (16): 1165–73. DOI: 10.1056/NEJM199910143411601
15. Pritchard J., Cotterill S.J., Germond S.M., Imeson J., de Kraker J., Jones D.R. High dose melphalan in the treatment of advanced neuroblastoma: results of a randomized trial (ENSG-1) by the European Neuroblastoma Study Group. Pediatr Blood Cancer 2005; 44 (4): 348–57. DOI: 10.1002/pbc.20219
16. Gurney J.G., Tersak J.M., Ness K.K., Landier W., Matthay K.K., Schmidt M.L. Children’s Oncology Group. Hearing loss, quality of life, and academic problems in longterm neuroblastoma survivors: a report from the Children’s Oncology Group. Pediatrics 2007; 120 (5): e1229–36. DOI: 10.1542/peds.2007-0178
17. Moreno L., Vaidya S.J., Pinkerton C.R., Ross Pinkerto C., Lewis I.J., Imeson J., et al.; European Neuroblastoma Study Group; Children’s Cancer and Leukaemia Group (CCLG) (formerly UKCCSG). Long-term follow-up of children with high-risk neuroblastoma: the ENSG5 trial experience. Pediatr Blood Cancer 2013; 60 (7): 1135–40. DOI: 10.1002/pbc.24452
