Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Clinical Studies

Children with chronic myeloid leukaemia treated with front-line imatinib have a slower molecular response and comparable survival compared with adults: a multicenter experience in Taiwan



The direct comparison of molecular responses of front-line imatinib (IM) monitored at the same laboratory between children and adults with chronic phase (CP) of chronic myeloid leukaemia (CML) had not been reported. In this multicenter study, we compared the landmark molecular responses and outcomes of paediatric and adult CML-CP cohorts treated with front-line IM in whom the BCR::ABL1 transcript levels were monitored at the same accredited laboratory in Taiwan.


Between June 2004 and July 2020, 55 newly diagnosed paediatric and 782 adult CML-CP patients, with molecular diagnosis and monitoring at the same reference laboratory in Taiwan, were enrolled. The criteria of 2020 European LeukemiaNet were applied to evaluate the molecular responses.


By year 5, the cumulative incidences of IS <1%, MMR, MR4.0 and MR4.5 of paediatric patients were all significantly lower than those of adult patients (58 vs 75%, 48 vs 66%, 25 vs 44%, 16 vs 34%, respectively). The 10-year progression-free survival (PFS) (90%) and overall survival (OS) (94%) of paediatric patients did not differ from those (92%) of adult patients.


We demonstrated the paediatric cohort had slower molecular responses to front-line IM and similar outcomes in 10-year PFS and OS in real-world practice.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Flow diagram of paediatric CML-CP cohort.
Fig. 2: Median BCR::ABL1 levels (IS) in paediatric and adult CML-CP treated with front-line imatinib.
Fig. 3: Cumulative incidences of landmarks of molecular response to front-line imatinib in paediatric and adult CML-CP.
Fig. 4: Outcomes of paediatric and adult CML-CP treated with front-line imatinib.

Data availability

The datasets generated and/or analysed during this study are available from the corresponding author on reasonable request.


  1. Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol. 2009;27:6041–51.

    Article  CAS  Google Scholar 

  2. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122:872–84.

    Article  CAS  Google Scholar 

  3. Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34:966–84.

    Article  CAS  Google Scholar 

  4. Zhen C, Wang YL. Molecular monitoring of chronic myeloid leukemia: international standardization of BCR-ABL1 quantitation. J Mol Diagn. 2013;15:556–64.

    Article  CAS  Google Scholar 

  5. Howlader N, Noone A, Krapcho M, Miller D, Bishop K, Altekruse S, et al. SEER Cancer Statistics Review, 1975-2013. Bethesda, MD: National Cancer Institute; 2016.

  6. Health Promotion Administration, Ministry of Health and Welfare: CANCER REGISTRY ANNUAL REPORT, 2014-2016 TAIWAN.

  7. de la Fuente J, Baruchel A, Biondi A, de Bont E, Dresse MF, Suttorp M, et al. Managing children with chronic myeloid leukaemia (CML): recommendations for the management of CML in children and young people up to the age of 18 years. Br J Haematol. 2014;167:33–47.

    Article  Google Scholar 

  8. Hijiya N, Schultz KR, Metzler M, Millot F, Suttorp M. Pediatric chronic myeloid leukemia is a unique disease that requires a different approach. Blood. 2016;127:392–9.

    Article  CAS  Google Scholar 

  9. Athale U, Hijiya N, Patterson BC, Bergsagel J, Andolina JR, Bittencourt H, et al. Management of chronic myeloid leukemia in children and adolescents: recommendations from the Children’s Oncology Group CML Working Group. Pediatr Blood Cancer. 2019;66:e27827.

    Article  Google Scholar 

  10. Hijiya N, Suttorp M. How I treat chronic myeloid leukemia in children and adolescents. Blood. 2019;133:2374–84.

    Article  CAS  Google Scholar 

  11. Millot F, Baruchel A, Guilhot J, Petit A, Leblanc T, Bertrand Y, et al. Imatinib is effective in children with previously untreated chronic myelogenous leukemia in early chronic phase: results of the French national phase IV trial. J Clin Oncol. 2011;29:2827–32.

    Article  CAS  Google Scholar 

  12. Giona F, Putti MC, Micalizzi C, Menna G, Moleti ML, Santoro N, et al. Long-term results of high-dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: the Italian experience. Br J Haematol. 2015;170:398–407.

    Article  CAS  Google Scholar 

  13. Janeczko-Czarnecka M, Krawczuk-Rybak M, Karpinska-Derda I, Niedzwiecki M, Musiol K, Cwiklinska M, et al. Imatinib in the treatment of chronic myeloid leukemia in children and adolescents is effective and well tolerated: report of the Polish Pediatric Study Group for the Treatment of Leukemias and Lymphomas. Adv Clin Exp Med. 2018;27:91–8.

    Article  Google Scholar 

  14. Suttorp M, Schulze P, Glauche I, Gohring G, von Neuhoff N, Metzler M, et al. Front-line imatinib treatment in children and adolescents with chronic myeloid leukemia: results from a phase III trial. Leukemia. 2018;32:1657–69.

    Article  CAS  Google Scholar 

  15. Pemmaraju N, Kantarjian H, Shan J, Jabbour E, Quintas-Cardama A, Verstovsek S, et al. Analysis of outcomes in adolescents and young adults with chronic myelogenous leukemia treated with upfront tyrosine kinase inhibitor therapy. Haematologica. 2012;97:1029–35.

    Article  CAS  Google Scholar 

  16. Proschmann R, Baldow C, Rothe T, Suttorp M, Thiede C, Tauer JT, et al. Response dynamics of pediatric patients with chronic myeloid leukemia on imatinib therapy. Haematologica. 2017;102:e39–e42.

    Article  Google Scholar 

  17. Castagnetti F, Gugliotta G, Baccarani M, Breccia M, Specchia G, Levato L, et al. Differences among young adults, adults and elderly chronic myeloid leukemia patients. Ann Oncol. 2015;26:185–92.

    Article  CAS  Google Scholar 

  18. Millot F, Guilhot J, Baruchel A, Petit A, Bertrand Y, Mazingue F, et al. Impact of early molecular response in children with chronic myeloid leukemia treated in the French Glivec phase 4 study. Blood. 2014;124:2408–10.

    Article  CAS  Google Scholar 

  19. Marin D, Ibrahim AR, Lucas C, Gerrard G, Wang L, Szydlo RM, et al. Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol. 2012;30:232–8.

    Article  CAS  Google Scholar 

  20. Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108:28–37.

    Article  CAS  Google Scholar 

  21. Cross NC, White HE, Ernst T, Welden L, Dietz C, Saglio G, et al. Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale. Leukemia. 2016;30:1844–52.

    Article  CAS  Google Scholar 

  22. Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood. 1984;63:789–99.

    Article  CAS  Google Scholar 

  23. Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G, et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood. 2011;118:686–92.

    Article  CAS  Google Scholar 

  24. Pfirrmann M, Baccarani M, Saussele S, Guilhot J, Cervantes F, Ossenkoppele G, et al. Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia. Leukemia. 2016;30:48–56.

    Article  CAS  Google Scholar 

  25. Kuo M-C, Chen T-Y, Wang M-C, Yang Y, Yeh S-P, Chang C-S, et al. No Differences in outcomes between patients achieving early molecular response at 3 months and those achieving optimal response at 6 or 12 months in chronic phase of chronic myeloid leukemia treated with front-line imatinib: Taiwan CML study. Blood. 2014;124:4544.

    Article  Google Scholar 

  26. Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376:917–27.

    Article  CAS  Google Scholar 

  27. Hehlmann R, Lauseker M, Saussele S, Pfirrmann M, Krause S, Kolb HJ, et al. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants. Leukemia. 2017;31:2398–406.

    Article  CAS  Google Scholar 

  28. Oehler VG. First-generation vs second-generation tyrosine kinase inhibitors: which is best at diagnosis of chronic phase chronic myeloid leukemia? Hematol Am Soc Hematol Educ Program. 2020;2020:228–36.

    Article  Google Scholar 

  29. Ganta RR, Nasaka S, Gundeti S. Impact of imatinib adherence on the cytogenetic response in pediatric chronic myeloid leukemia—chronic phase. Indian J Pediatr. 2016;83:1009–12.

    Article  Google Scholar 

  30. Shao H, Zeng Z, Cen J, Zhang J, Bai S, Wu C, et al. The impact of early molecular response in children and adolescents with chronic myeloid leukemia treated with imatinib: a single-center study from China. Leuk Lymphoma. 2018;59:2152–8.

    Article  CAS  Google Scholar 

  31. Lakshmaiah KC, Bhise R, Purohit S, Abraham LJ, Lokanatha D, Suresh TM, et al. Chronic myeloid leukemia in children and adolescents: results of treatment with imatinib mesylate. Leuk Lymphoma. 2012;53:2430–3.

    Article  CAS  Google Scholar 

  32. Ganguly S, Pushpam D, Mian A, Chopra A, Gupta R, Bakhshi S. Real-world experience of imatinib in pediatric chronic phase chronic myeloid leukemia: a single-center experience from India. Clin Lymphoma Myeloma Leuk. 2020;20:e437–e44.

    Article  Google Scholar 

  33. Madabhavi I, Patel A, Modi G, Anand A, Panchal H, Parikh S. Pediatric chronic myeloid leukemia: a single-center experience. J Cancer Res Ther. 2020;16:110–5.

    Article  CAS  Google Scholar 

  34. Deng M, Guan X, Wen X, Xiao J, An X, Yu J. Clinical efficacy and safety of imatinib treatment in children and adolescents with chronic myeloid leukemia: a single-center experience in China. Medicine. 2020;99:e19150.

    Article  Google Scholar 

  35. Cai Y, Liu C, Guo Y, Chen X, Zhang L, Chen Y, et al. Long-term safety and efficacy of imatinib in pediatric patients with chronic myeloid leukemia: single-center experience from China. Int J Hematol. 2021;113:413–21.

  36. Champagne MA, Fu CH, Chang M, Chen H, Gerbing RB, Alonzo TA, et al. Higher dose imatinib for children with de novo chronic phase chronic myelogenous leukemia: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2011;57:56–62.

    Article  Google Scholar 

  37. Branford S, Kim DDH, Apperley JF, Eide CA, Mustjoki S, Ong ST, et al. Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia. Leukemia. 2019;33:1835–50.

    Article  Google Scholar 

  38. Ernst T, Busch M, Rinke J, Ernst J, Haferlach C, Beck JF, et al. Frequent ASXL1 mutations in children and young adults with chronic myeloid leukemia. Leukemia. 2018;32:2046–9.

    Article  CAS  Google Scholar 

  39. Roche-Lestienne C, Marceau A, Labis E, Nibourel O, Coiteux V, Guilhot J, et al. Mutation analysis of TET2, IDH1, IDH2 and ASXL1 in chronic myeloid leukemia. Leukemia. 2011;25:1661–4.

    Article  CAS  Google Scholar 

  40. Schonfeld L, Rinke J, Hinze A, Nagel SN, Schafer V, Schenk T, et al. ASXL1 mutations predict inferior molecular response to nilotinib treatment in chronic myeloid leukemia. Leukemia. 2022;36:2242–9.

    Article  Google Scholar 

  41. Thornley I, Perentesis JP, Davies SM, Smith FO, Champagne M, Lipton JM. Treating children with chronic myeloid leukemia in the imatinib era: a therapeutic dilemma? Med Pediatr Oncol. 2003;41:115–7.

    Article  Google Scholar 

  42. Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N. Engl J Med. 2006;355:2408–17.

    Article  CAS  Google Scholar 

  43. de Lavallade H, Apperley JF, Khorashad JS, Milojkovic D, Reid AG, Bua M, et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol. 2008;26:3358–63.

    Article  Google Scholar 

  44. Hochhaus A, O’Brien SG, Guilhot F, Druker BJ, Branford S, Foroni L, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia. 2009;23:1054–61.

    Article  CAS  Google Scholar 

  45. Pfirrmann M, Clark RE, Prejzner W, Lauseker M, Baccarani M, Saussele S, et al. The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia. Leukemia. 2020;34:2138–49.

    Article  Google Scholar 

  46. Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst. 1998;90:850–8.

    Article  CAS  Google Scholar 

  47. Gurrea Salas D, Glauche I, Tauer JT, Thiede C, Suttorp M. Can prognostic scoring systems for chronic myeloid leukemia as established in adults be applied to pediatric patients? Ann Hematol. 2015;94:1363–71.

    Article  Google Scholar 

  48. Millot F, Guilhot J, Suttorp M, Gunes AM, Sedlacek P, De Bont E, et al. Prognostic discrimination based on the EUTOS long-term survival score within the International Registry for Chronic Myeloid Leukemia in children and adolescents. Haematologica. 2017;102:1704–8.

    Article  CAS  Google Scholar 

  49. Leung WY, Cheuk DK, Cheng FW, Leung AW, Chiu KH, Ho KK, et al. Outcome prediction of chronic myeloid leukemia (CML) in children. Ann Hematol. 2022;101:1677–88.

    Article  CAS  Google Scholar 

Download references


The authors would like to thank Ms. Chang-Liang Lai for her technical assistance; and Drs Fang-Liang Huang, Tsung-Yen Chang, Te-Kau Chang, Tseng-Hsi Lin, Ching-Yuan Kuo, Chih-Cheng Chen, Ming-Sun Yu, Hung-I Cheng, and Yu-Shin Hung for providing patient samples.


This work was supported by grants from Chang Gung Memorial Hospital, Taiwan (CMRPG350071 and XMRPG1A0081).

Author information

Authors and Affiliations



H-CL and M-CK: provision of materials, data curation and writing of the manuscript. K-HW, T-YC, J-SC, M-CW, T-LL, YSY, M-CM, P-NW, J-MS, S-CW, S-HC, T-HJ, C-NC and T-CY: provision of materials and approval of the manuscript. T-HL: data analysis and approval of the manuscript. L-YS: concept design, methodology, funding acquisition, supervision, data curation and writing of the manuscript.

Corresponding author

Correspondence to Lee-Yung Shih.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Written informed consent was obtained from the patients, parents, or guardians. Chang Gung Medical Foundation Institutional Review Board approved the study and the committee’s reference numbers are 96-0358B and 100-0927B. This study was performed in accordance with the Declaration of Helsinki.

Consent to publish

Not applicable.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, HC., Kuo, MC., Wu, KH. et al. Children with chronic myeloid leukaemia treated with front-line imatinib have a slower molecular response and comparable survival compared with adults: a multicenter experience in Taiwan. Br J Cancer (2023).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI:


Quick links