3-year survival rate in acute lymphoblastic leukemia: comparison of ALL-2006 and ALL-2013 Protocols

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Avyandita Meirizkia
Dewi Rosariah Ayu
Raden Muhammad Indra
Dian Puspita Sari


Background With advances in supportive and risk-stratified therapy, the 5-year survival rate of acute lymphoblastic leukemia has reached 85.5%. The ALL-2006 treatment protocol was modified and renamed the ALL-2013 protocol, with dose and duration changes.

Objective To compare outcomes of the ALL-2006 and ALL-2013 protocols, with regards to mortality, remission, relapse, and three-year survival rates.

Methods This was retrospective cohort study. Subjects were acute lymphoblastic leukemia (ALL) patients treated from 2011 to 2018 in Mohamad Hoesin Hospital, Palembang, South Sumatera. The three-year survival rates, relapse, remission rates and comparison of ALL-2006 and ALL-2013 protocols were analyzed with Kaplan-Meier method.

Results Mortality was significantly correlated with age at diagnosis <1 year and >10 years, hyperleukocytosis, and high-risk disease status. Patients aged 1 to 10 years, with leukocyte count <50,000/mm3 and standard-risk status had significantly higher likelihood of achieving remission. Mortality was not significantly different between the ALL-2006 protocol group [70.6%; mean survival 1,182.15 (SD 176.89) days] and the ALL-2013 protocol group [72.1%; mean survival 764.23 (SD 63.49) days]; (P=0.209). Remission was achieved in 39.2% of the ALL-2006 group and 33% of the ALL-2013 group (P>0.05). Relapse was also not significantly different between the two groups (ALL-2006: 29.4% vs. ALL-2013: 17.9%; P>0.05). Probability of death in the ALL-2006 group was 0.3 times lower than in the ALL-2013 group (P<0.05), while that of the high-risk group was 3 times higher. Remission was 2.19 times higher in those with leukocyte <50,000/mm3 compared to those with hyperleukocytosis. In addition, relapse was significantly more likely in high-risk patients (HR 2.96; 95%CI 1.22 to 7.19). Overall, the 3-year survival rate was 33%, with 41.7% in the ALL-2006 group and 30.7% in the ALL-2013 group.

Conclusion Three-year survival rate of ALL-2006 protocol is higher than that of ALL-2013 protocol but is not statistically significant.  Age at diagnosis <1 year and >10 years, hyperleukocytosis, and high-risk group are significantly correlated with higher mortality and lower remission rates. However, these three factors are not significantly different in terms of relapse.   

Article Details

How to Cite
Meirizkia A, Ayu D, Indra R, Sari D. 3-year survival rate in acute lymphoblastic leukemia: comparison of ALL-2006 and ALL-2013 Protocols. PI [Internet]. 18May2021 [cited 25Jul.2021];61(3):155-4. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/2553
Pediatric Hemato-Oncology
Received 2020-12-02
Accepted 2021-05-18
Published 2021-05-18


1. Ma H, Sun H, Sun X. Survival improvement by decade of patients aged 0-14 years with acute lymphoblastic leukemia: a SEER anaylsis. Sci Rep. 2014;4:4227. DOI: 10.1038/srep04227.
2. Yakin R, Syarif S, Tehuteru ES. Perbandingan kesintasan tiga tahun pada anak leukemia limfoblastik akut antara protokol pengobatan 2006 dan 2013. Indones J Cancer. 2017;11:111-8. DOI: 10.33371/ijoc.v11i3.515.
3. Widiaskara I, Permono B, Ugrasena I, Mia R. Luaran pengobatan fase induksi pasien leukemia limfoblastik akut pada anak di Rumah Sakit Umum Dr. Soetomo Surabaya. Sari Pediatri. 2010;12:128-34. DOI: 10.14238/sp12.2.2010.128-34.
4. Permono B, Ugrasena I, Supriyadi E. Leukemia akut. In: Windiastuti E, Nency YM, Mulatsih S, Sudarmanto B, Ugrasena IDG, editors. Buku ajar hemato onkologi anak. Jakarta: Badan Penerbit IDAI; 2018. p. 276-85.
5. Gutierrez A, Silverman LB. Acute lymphoblastic leukemia. In: Orkin SH, Fisher DE, Ginsburg D, Look AT, editors. Nathan and Oski’s hematology and oncology of infancy. Vol 2. 8th ed. Philadelphia: Elsevier; 2015. p. 1527-52.
6. Bathia S, Robinson L. Epidemiology of leukemia in childhood. In: Nathan D, Orkin S, Ginsburg D, Look A, editors. Nathan and Oski’s hematology of infancy and childhood. 6th ed. Philadelphia: Saunders; 2003. p. 1081-100.
7. Whitlock J, Gaynon P. Acute lymphoblastic leukemia. In: Greer J, Forester J, Lukens J, Rodgers J, Paraskevas F, Glader B, editors. Wintrobe’s clinical hematology. 11th ed. Philadelphia: Williams & Wilkins; 2004. p. 2143-59.
8. Budiyanto W, Mulatsih S, Sutaryo. Luaran terapi pasien leukemia limfoblastik akut dengan leukosit >50.000/ul di RSUP Dr. Sardjito Februari 1999 - Februari 2009. Sari Pediatri. 2009;10:410-6. DOI: 10.14238/sp10.6.2009.410-6.
9. Perdani RR, Sudarmanto B. Hematological parameters and remission induction of childhood acute lymphoblastic leukemia. Paediatr Indones. 2018;58:71-4. DOI: 10.14238/pi58.2.2018.71-4.
10. Lieberman F, Villgran V, Normolle D, Boyiadzis M. Intracranial hemorrhage in patients newly diagnosed with acute myeloid leukemia and hyperleukocytosis. Acta Haemotol. 2017;138:116-8. DOI: 10.1159/000478690.
11. Wijayanti LP, Supriyadi E. Faktor prognostik dan kesintasan pasien leukemia limfoblastik akut anak di RSUP dr. Sardjito, Yogyakarta 2010-2015. Indones J Cancer. 11:145-50. DOI: 10.33371/ijoc.v11i4.532.
12. Smith M, Arthur D, Carmitta B, Carrol A, Crist W, Gaynon P, et al. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol. 1996;14:18-24. DOI: 10.1200/JCO.1996.14.1.18.
13. Hossain MJ, Xie L, McCahan S. Characterization of pediatric acute lymphoblastic leukemia survival patterns by age at diagnosis. J Cancer Epidemiol. 2014;2014:865979. DOI: 10.1155/2014/865979.
14. Hao TK, Hiep PN, Hoa N, Ha CV. Causes of death in childhood acute lymphoblastic leukemia at Hue Central Hospital for 10 years (2008-2018). Glob Pediatr Health. 2020;7:1-8. DOI: 10.1177/2333794X20901930.
15. Alfina D, Wudjajanti PH, Patria SY. The outcomes of childhood acute lymphoblastic leukemia with hyperleukocytosis. Paediatr Indones. 2018;58:186-91. DOI: 10.14238/pi58.4.2018.186-91.
16. de Sousa D, Ferreira F, Felix F, Lopes M. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival. Braz J Hematol Hemotherapy. 2015;37:223-9. DOI: 10.1016/j.bjhh.2015.03.009.
17. Vrooman LM, Silverman LB. Treatment of childhood acute lymphoblastic leukemia: prognostic factors and clinical advances. Curr Hematol Malig Rep. 2016;11:385-94. DOI: 10.1007/s11899-016-0337-y.
18. Permatasari E, Windiastuti E, Satari H. Survival and prognostic factors of childhood acute lymphoblastic leukemia. Pediatr Indones. 2009;49:365-71. 10.14238/pi49.6.2009.365-71.
19. Oskarsson T, Soderhall S, Ardvison J, Forestier E, Montgomery S, Bottai M, et al. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment, and outcome. Haematologica. 2016;101:68-76. DOI: 10.3324/haematol.2015.131680.
20. Jaime-Perez C, Pinzon-Uresti MA, Jimenez-Castillo RA, Colunga-Pedraza JE, Gonzalez-Liano O, Gomez-Almaguer D. Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor. Hematology. 2018;23:1-9. DOI: 10.1080/10245332.2017.1333294.
21. Bathia S, Landier W, Hageman L, Kim H, Chen Y, Crews K, et al. 6MP adherence in a multiracial cohort of children with acute lymphoblastic leukemia: a Children’s Oncology Group study. Blood. 2014;124:2345-55. DOI: 10.1182/blood-2014-01-552166.
22. Egler RA, Ahuja SP, Matloub Y. L-asparaginase in the treatment of patients with acute lymphoblastic leukemia. J Pharmacol Pharmacother. 2016:7:62-71. DOI: 10.4103/0976-500X.184769.
23. Muller H, Boos J. Use of L-asparaginase in childhood ALL. Crit Rev Oncol Hematol. 1998;28:97-113. DOI: 10.1016/s1040-8428(98)00015-8.
24. Tehuteru ES. Gambaran tingkat remisi pada leukemia limfoblastik akut setelah fase induksi di bangsal kanker anak RS Kanker Dharmais. Indones J Cancer. 2011;5:159-62. DOI: 10.33371/ijoc.v5i4.190.
25. Noone AM, Howlader N, Krapcho M, Miller D, Brest A, Yu M, et al. (eds). SEER Cancer Statistics Review, 1975-2015, National Cancer Institute. Bethesda, MD. [cited 2020 May 15]. Available from: https://seer.cancer.gov/csr/1975_2015/, based on November 2017 SEER data submission, posted to the SEER web site, April 2018.