Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2025; 24: 78-87
Результаты лечения острого промиелоцитарного лейкоза у детей в Российской Федерации и Республике Беларусь по протоколам ОПЛ 2003/2008
https://doi.org/10.24287/1726-1708-2025-24-1-78-87Аннотация
В работе представлены результаты терапии 339 пациентов с острым промиелоцитарным лейкозом (ОПЛ), получивших лечение в 57 регионах Российской Федерации (РФ) и Республике Беларусь (РБ) по протоколам ОПЛ 2003/2008 с 2008 г. по 1 января 2024 г. На основании протокола ОМЛ-MRD-2018 выполнена оценка доли ОПЛ в структуре острого миелоидного лейкоза (ОМЛ) у детей в РФ. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России. Установлено, что доля ОПЛ в структуре ОМЛ составила 26%, причем встречаемость ОПЛ в различных регионах РФ неоднородна. Полученные результаты свидетельствуют о более высокой заболеваемости ОПЛ у детей в РФ, чем в Европе и США, однако это требует дальнейшего подтверждения в эпидемиологических исследованиях. Показатели 5-летней общей (ОВ) и бессобытийной (БСВ) выживаемости у пациентов, получивших лечение по протоколам ОПЛ 2003/2008, составили 82% (95% доверительный интервал (ДИ) 78–86) и 73% (95% ДИ 67–78) соответственно. В группе низкого риска (ГНР) 5-летняя ОВ и БСВ были статистически значимо выше, чем в группе высокого риска (ГВР), и составили: ОВ – 93% (95% ДИ 89–97) и 63% (95% ДИ 55–72) (p < 0,001) соответственно, БСВ – 85% (95% ДИ 79–91) и 52% (95% ДИ 44–63) (p < 0,001) соответственно. Риск рецидива был выше в ГВР: 15% (95% ДИ 9,1–25) против 8,7% (95% ДИ 4,9–15) в ГНР (p < 0,045). Различия в показателях выживаемости в ГНР и ГВР были обусловлены высокой смертностью в индукции ремиссии в ГВР по сравнению с ГНР – 30,1% и 2,9% соответственно, причем причиной 83,7% смертей было кровоизлияние в мозг. Снижение показателей ранней смерти является ключевым для улучшения результатов лечения ОПЛ у детей в РФ и РБ.
Список литературы
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2. Maule M., Dama E., Mosso M.L., Magnani C., Pastore G., Merletti F. High incidence of acute promyelocytic leukemia in children in northwest Italy, 1980–2003: A report from the Childhood Cancer Registry of Piedmont. Leukemia 2008; 22: 439– 41.
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22. Sanz M.A., Fenaux P., Tallman M.S., Estey E.H., Lowenberg B., Naoe T., et al. Management of Acute Promyelocytic Leukemia: Updated Recommendations from an Expert Panel of the European LeukemiaNet. Blood 2019; 133: 1630–43.
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24. Zheng H., Jiang H., Hu S., Liao N., Shen D., Tian X., et al. Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLGAPL2016 Protocol Study. J Clin Oncol 2021; 39: 3161–70.
Pediatric Hematology/Oncology and Immunopathology. 2025; 24: 78-87
Outcomes of treatment of childhood acute promyelocytic leukemia according to the APL 2003/2008 protocols in Russia and Belarus
https://doi.org/10.24287/1726-1708-2025-24-1-78-87Abstract
This study presents the results of treatment of 339 patients with acute promyelocytic leukemia (APL) from 57 regions of the Russian Federation (RF) and the Republic of Belarus (RB) according to the 2003/2008 APL treatment protocols, from 2008 to 1 January 2024. Based on the data from the AML-MRD-2018 protocol, the proportion of APL among childhood acute myeloid leukemia (AML) cases in the RF was investigated. 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. It was established that the APL cases comprised 26% of AML cases, and APL incidence rate varied across the regions of the RF. Our findings suggest that the incidence of APL in Russian children is higher than in children from Europe and the USA, but further epidemiological research is needed to confirm this. The 5-year overall (OS) and event-free (EFS) survival rates in the patients treated according to the 2003/2008 APL protocols were 82% (95% confidence interval (CI) 78–86) and 73% (95% CI 67–78), respectively. In the low-risk group (LRG) the five-year OS and EFS rates were statistically significantly higher than in the high-risk group (HRG), with 5-year OS reaching 93% (95% CI 89–97) in the LRG and 63% (95% CI 55–72) (p < 0.001) in the HRG, and EFS – 85% (95% CI 79–91) and 52% (95% CI 44–63) (p < 0.001), respectively. The risk of relapse was higher in the HRG: 15% (95% CI 9.1–25) in the HRG vs 8.7% (95% CI 4.9–15%) in the LRG (p < 0.045). The difference in the survival rates in the LRG and HRG was attributable to a higher mortality rate during remission induction in the HRG as compared to the LRG: 30.1% and 2.9%, respectively. Notably, 83.7% of deaths were caused by brain haemorrhage. Decreasing early death rate is key to improving APL treatment results in children in the RF and RB.
References
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2. Maule M., Dama E., Mosso M.L., Magnani C., Pastore G., Merletti F. High incidence of acute promyelocytic leukemia in children in northwest Italy, 1980–2003: A report from the Childhood Cancer Registry of Piedmont. Leukemia 2008; 22: 439– 41.
3. Zhang L., Samad A., Pombo-de-Oliveira M.S., Scelo G., Smith M.T., Feusner J., et al. Global Characteristics of Childhood Acute Promyelocytic Leukemia. Blood Rev 2015; 29 (2): 101–25.
4. Corea A.M., Espinoza C.P., Rajnoldi A.C., Conter V., Lietti G., Masera G., et al. Childhood acute promyelocytic leukemia in Nicaragua. Ann Oncol 1993; 4: 892–4.
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6. Ribeiro R.C., Rego E. Management of APl in developing countries: epidemiology, challenges and opportunities for international collaboration. Hematology Am Soc Hematol Educ Program 2006: 162–8.
7. Rajpurkar M., Alonzo T.A., Wang Y.-C., Gerbing R.B., Gamis A.S., Feusner J.H., et al. Risk markers for significant bleeding and thrombosis in pediatric acute promyelocytic leukemia. Report from the Children’s Oncology Group study AAML0631. J Pediatr Hematol 2019; 41: 51–5.
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14. Gabert J., Beillard E., van der Velden V., Bi W., Grimwade D., Pallisgaard N., et al. Standardization and quality control studies of ‘realtime’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – A Europe Against Cancer Program. Leukemia 2003; 17: 2318–57.
15. Testi A.M., D’Angiò M., Locatelli F., Pession A., Lo Coco F. Acute Promyelocytic Leukemia (APL): Comparison Between Children and Adults. Mediterr J Hematol Infect Dis 2014; 6 (1): e2014032.
16. Chen Y., Kantarjian H., Wang H., Cortes J., Ravandi F. Acute promyelocytic leukemia: A population-based study on incidence and survival in the United States, 1975–2008. Cancer 2012; 118: 5811–8.
17. Zhang L., Zhu X. Epidemiology, diagnosis and treatment of acute promyelocytic leukemia in children: the experience in China. Mediterr J Haematol Infect Dis 2012; 4 (1): e2012012.
18. So C.C., Wan T.S., Chow J.L., Hui K.-C., Choi W.W., Lam C.C., Chan L.-C. A single-center cytogenetic study of 629 Chinese patients with de novo acute myeloid leukemia-evidence of major ethnic differences and a high prevalence of acute promyelocytic leukemia in Chinese patients. Cancer Genet 2011; 204: 430–8.
19. Abla O., Ribeiro R.C., Testi A.M., Montesinos P., Creutzig U., Sung L., et al. Predictors of thrombohemorrhagic early death in children and adolescents with t(15;17)-positive acute promyelocytic leukemia treated with ATRA and chemotherapy. Ann Hematol 2017; 96 (9): 1449–56.
20. Liu Y., Wang Z., Jiang M., Dai L., Zhang W., Wu D., Ruan C. The expression of annexin II and its role in the fibrinolytic activity in acute promyelocytic leukemia. Leukemia Res 2011; 35 (7): 879–84.
21. Hermsen J., Hambley B. The Coagulopathy of Acute Promyelocytic Leukemia: An Updated Review of Pathophysiology, Risk Stratification, and Clinical Management. Cancers 2023; 15: 3477.
22. Sanz M.A., Fenaux P., Tallman M.S., Estey E.H., Lowenberg B., Naoe T., et al. Management of Acute Promyelocytic Leukemia: Updated Recommendations from an Expert Panel of the European LeukemiaNet. Blood 2019; 133: 1630–43.
23. Kutny M.A., Alonzo T.A., Abla O., Rajpurkar M., Gerbing R.B., Wang Y.-C., et al. Assessment of Arsenic Trioxide and All-trans Retinoic Acid for the Treatment of Pediatric Acute Promyelocytic Leukemia A Report From the Children’s Oncology Group AAML1331 Trial. JAMA Oncol 2022; 8 (1): 79–87.
24. Zheng H., Jiang H., Hu S., Liao N., Shen D., Tian X., et al. Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLGAPL2016 Protocol Study. J Clin Oncol 2021; 39: 3161–70.
