Outcomes of treatment of childhood acute promyelocytic leukemia according to the APL 2003/2008 protocols in Russia and Belarus

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Abstract

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.

About the authors

O. V. Aleinikova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation; The Republican Medical Research Center of Pediatric Oncology, Hematology and Immunology of Ministry of Health of the Republic of Belarus

Author for correspondence.
ORCID iD: 0000-0001-8384-5073

Moscow, Minsk

Russian Federation

M. N. Sadovskaya

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-7918-680X

Moscow

Russian Federation

D. D. Baydildina

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-7130-8596

Moscow

Russian Federation

A. M. Popov

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-0889-6986

Moscow

Russian Federation

E. A. Zerkalenkova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-9634-5828

Moscow

Russian Federation

Yu. V. Olshanskaya

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-2352-7716

Moscow

Russian Federation

E. A. Rudkova

The Republican Medical Research Center of Pediatric Oncology, Hematology and Immunology of Ministry of Health of the Republic of Belarus

Minsk

Belarus

M. E. Dubrovina

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-8228-4876

Moscow

Russian Federation

K. A. Voronin

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-7578-9657

Moscow

Russian Federation

E. V. Samochatova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Moscow

Russian Federation

G. A. Novichkova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-2322-5734

Moscow

Russian Federation

A. A. Maschan

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-0016-6698

Moscow

Russian Federation

References

  1. Zhang L., Zhu X. Epidemiology, Diagnosis and Treatment of Acute Promyelocytic Leukemia in Children: the Experience in China. Mediterr J Hematol Infect Dis 2012; 4 (1): e2012012.
  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.
  5. Gómez S.M., Schuttenberg V., Armendariz H., Alba L., Martinez M., Fynn A., et al. Childhood acute leukemia: A single institution experience in La Plata, Argentina. Med. Pediatr Oncol 2001; 36: 383–5.
  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.
  8. Gurnari С., Voso M.T., Girardi K., Mastronuzzi A., Strocchio L. Acute promyelocytic leukemia in children: a model of precision medicine and chemotherapy-free therapy. Int J Mol Sci 2021; 22: 642.
  9. Lo-Coco F., Hasan S.K. Understanding the molecular pathogenesis of acute promyelocytic leukemia. Best Pract Res Clin Haematol 2014; 27: 3–9.
  10. Mikhailova E.V., Mochalova N.S., Kashpor S.A., Zerkalenkova E.A., Konyukhova T.V., Plyasunova S.A., et al. Low specificity of HLA-DR expression for diagnosis of acute promyelocytic leukemia. Pediatric Hematology/Oncology and Immunopathology 2022; 21 (1): 42–8. (In Russ.). doi: 10.24287/1726-1708-2022-211-42-48
  11. Kutny M.A., Gregory J. Jr, Feusner J.H. Treatment of paediatric APL: how does the therapeutic approach differ from adults? Best Pract Res Clin Haematol 2014; 27 (1): 69–78.
  12. Testi A.M., Pession A., Diverio D., Grimwade D., Gibson B., de Azevedo A.C., et al. Risk-adapted treatment of acute promyelocytic leukemia: Results from the International Consortium for Childhood APL. Blood 2018; 132: 405–12.
  13. Samochatova E.V., Baydildina D.D., Maschan M.A., Savva N.N., Khlebnikova O.P., Shamardina A.V., et al. Effectiveness of childhood acute promyelocytic leukemia treatment with all-trans retinoic acid, cytosine arabinoside and reduced doses of anthracyclines. Oncohematology 2008; (3): 8–17. (In Russ.).
  14. Gabert J., Beillard E., van derVelden 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.

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Copyright (c) 2025 Aleinikova O.V., Sadovskaya M.N., Baydildina D.D., Popov A.M., Zerkalenkova E.A., Olshanskaya Y.V., Rudkova E.A., Dubrovina M.E., Voronin K.A., Samochatova E.V., Novichkova G.A., Maschan A.A.

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