Hematopoietic cell transplantation in pediatric chronic myeloid leukemia
DOI:
https://doi.org/10.46765/2675-374X.2025v6n1e301Keywords:
Pediatrics, Leukemia, Myeloid, Hematopoietic Stem Cell TransplantationAbstract
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder primarily linked to the BCR-ABL fusion gene, resulting from the Philadelphia chromosome translocation. While rare in pediatric populations, CML in children presents unique biological and clinical features, often diagnosed incidentally through leukocytosis. Symptoms may include fatigue, weight loss, and splenomegaly, with advanced cases exhibiting signs of bleeding and infections. The management of pediatric CML has evolved significantly with the introduction of tyrosine kinase inhibitors (TKIs), in which imatinib remains the first-line treatment despite potential long-term toxicities. Second-generation TKIs such as dasatinib and nilotinib are alternatives for treatment resistance. Asciminib, a third-generation inhibitor, shows promise for cases resistant to other TKIs, although pediatric data are still emerging. Allogeneic hematopoietic cell transplantation (HCT) is crucial for highrisk pediatric CML cases, particularly in the blastic phase or in instances of TKI resistance. The choice of conditioning regimens, whether myeloablative or reduced-intensity, is vital, with busulfan-based regimens preferred due to lower late effects. Post-transplant, the use of TKIs can be beneficial, with molecular monitoring guiding treatment decisions. Overall, individualization of therapy considering disease phase, molecular profile, and donor availability is essential for optimizing outcomes in pediatric CML management. Close follow-up strategies involving regular molecular assessments and tailored therapeutic approaches post-HCT are critical for improving patient survival rates and managing relapses.
References
1. Millot F, Guilhot J, Suttorp M, Güneş AM, Sedlacek P, De Bont E, Li CK, Kalwak K, Lausen B, Culic S, Dworzak M, Kaiserova E, De Moerloose B, Roula F, Biondi A, Baruchel A. 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(10):1704–8. https://doi.org/10.3324/haematol.2017.170035 DOI: https://doi.org/10.3324/haematol.2017.170035
2. Ford M, Mauro M, Aftandilian C, Sakamoto KM, Hijiya N. Management of chronic myeloid leukemia in children and young adult. Curr Hematol Malig Rep. 2022;17:121–6. https://doi.org/10.1007/s11899-022-00673-5 DOI: https://doi.org/10.1007/s11899-022-00673-5
3. Hijiya N, Suttorp M. How I treat chronic myeloid leukemia in children and adolescents. Blood. 2019; 133(22):2374–84. https://doi.org/10.1182/blood.2018882233 DOI: https://doi.org/10.1182/blood.2018882233
4. Inoue A, Imamura CK, Shimada H, Katayama D, Urabe K, Suzuki R, Takitani K, Ashida A. Pharmacokinetics, efficacy and safety of bosutinib in a pediatric with chronic myeloid leukemia. J Pediatr Pharmacol Ther. 2020;25(8):742–5. https://doi.org/10.5863/1551-6776-25.8.742 DOI: https://doi.org/10.5863/1551-6776-25.8.742
5. Kodama Y, Sato A, Kato K, Sakaguchi H, Kato M, Kawasaki H, Hiramatsu H, Kato I, Taga T, Shimada H. Ponatinib in pediatric patients with Philadelphia chromosome-positive leukemia: a retrospective survey of the Japan children’s Cancer Group. Int J Hematol. 2022;116(1):131–8. https://doi.org/10.1007/s12185-022-03329-5 DOI: https://doi.org/10.1007/s12185-022-03329-5
6. Millot F, Suttorp M, Versluys AB, Kalwak K, Nelken B, Ducassou S, Bertrand Y, Baruchel A. Ponatinib in childhood Philadelphia chromosome-positive leukaemias: an international registry of childhood chronic myeloid leukaemia study. Eur J Cancer. 2020;136:107–12 https://doi.org/10.1016/j.ejca.2020.05.020 DOI: https://doi.org/10.1016/j.ejca.2020.05.020
7. Hijiya N, Mauro MJ. Asciminib in the treatment of Philadelphia chromosome-positive cronic myeloid leukemia: Focus on patient selection and outcomes. Cancer Manag Res. 2023;15:873-91. https://doi.org/10.2147/CMAR.S353374 DOI: https://doi.org/10.2147/CMAR.S353374
8. Hijiya N, Kapoor S, Hoch M, Descamps L, Dhamal V, Cardoso APT. ASC4KIDS: A multicenter, open-label, phase Ib/II study to determine the dose and safety of Asciminib in pediatric patients with chronic myeloid leukemia in the chronic phase. The 65th ASH Annual Meeting Abstracts. Blood. 2023;142(Suppl.1):6387. https://doi.org/10.1182/blood-2023-185535 DOI: https://doi.org/10.1182/blood-2023-185535
9. Shimada H, Tanizawa A, Kondo T, Nagamura-Inoue T, Yasui M, Tojo A, Muramatsu H, Eto T, Doki N, Tanaka M, Sato M, Noguchi M, Uchida N, Takahashi Y, Sakata N, Ichinohe T, Hashii Y, Kato K, Atsuta Y, Ohashi K; Pediatric and Adult CML/MPN Working Groups of the Japanese Society for Transplantation and Cellular Therapy. Prognostic factors for outcomes of allogeneic HSCT for children and adolescents/young adults with CML in the TKI era. Transplant Cell Ther. 2022;28(7):376–89. https://doi.org/10.1016/j.jtct.2022.04.011 DOI: https://doi.org/10.1016/j.jtct.2022.04.011
10. Millot F, Esperou H, Bordigoni P, Dalle JH, Michallet M, Michel G, Bourhis JL, Kuenz M, Blaise D, Garban F, Plouvier E, Rome A, Guilhot J, Guilhot F. Allogeneic bone marrow transplantation for chronic myeloid leukemia in childhood: a report from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). Bone Marrow Transplantation. 2003;32(10):993–9. https://doi.org/10.1038/sj.bmt.1704255 DOI: https://doi.org/10.1038/sj.bmt.1704255
11. Cwynarski K, Roberts IA, Iacobelli S, van Biezen A, Brand R, Devergie A, Vossen JM, Aljurf M, Arcese W, Locatelli F, Dini G, Niethammer D, Niederwieser D, Apperley JF; Paediatric and Chronic Leukaemia Working Parties of the European Group for Blood and Marrow Transplantation. Stem cell transplantation for chronic myeloid leukemia in children. Blood. 2003;102(4):1224–31. https://doi.org/10.1182/blood-2002-12-3637 DOI: https://doi.org/10.1182/blood-2002-12-3637
12. Hafez HA, Abdallah A, Hammad M, Hamdy N, Yassin D, Salem S, Hassanain O, Elhalaby L, Elhaddad A. Outcomes of allogenic hematopoietic cell transplantation for childhood chronic myeloid leukemia: single-center experience. Pediatr Transplant. 2020;24(4):e13664. https://doi.org/10.1111/petr.13664 DOI: https://doi.org/10.1111/petr.13664
13. Ishida H, Shimada H, Tanizawa A, Shimazu Y, Tachibana T, Doki N, Ara T, Matsuo Y, Nara M, Toubai T, Ino K, Nakamae H, Kato K, Kato K, Sato A, Hino M, Matsumoto K, Atsuta Y, Yasui M, Nagamura-Inoue T. Allogeneic stem cell transplantation for children and adolescents/young adults with de novo blastic phase chronic myeloid leukemia in the tyrosine kinase inhibitor era. Am J Hematol. 2023;98(8):E200–3. https://doi.org/10.1002/ajh.26959 DOI: https://doi.org/10.1002/ajh.26959
14. Onida F, de Wreede LC, van Biezen A, Eikema DJ, Byrne JL, Iori AP, Schots R, Jungova A, Schetelig J, Finke J, Veelken H, Johansson JE, Craddock C, Stelljes M, Theobald M, Holler E, Schanz U, Schaap N, Bittenbring J, Olavarria E, Chalandon Y, Kröger N. Allogeneic stem cell transplantation in patients with atypical chronic myeloid leukaemia: a retrospective study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation. Br J Haematol. 2017;177(5):759–65. https://doi.org/10.1111/bjh.14619 DOI: https://doi.org/10.1111/bjh.14619
15. Fraint E, Abdel-Azim H, Bhatt NS, Broglie L, Chattha A, Kohorst M, Ktena YP, Lee MA, Long S, Qayed M, Sharma A, Stefanski H, Vatsayan A, Wray L, Hamadani M, Carpenter PA. Evaluation of children with malignancies for blood and marrow transplantation: a report from the ASTCT Committee on Practice Guidelines. Transplant Cell Ther. 2023;29(5):293–301. https://doi.org/10.1016/j.jtct.2023.02.003 DOI: https://doi.org/10.1016/j.jtct.2023.02.003
16. Sembill S, Ampatzidou M, Chaudhury S, Dworzak M, Kalwak K, Karow A, Kiani A, Krumbholz M, Luesink M, Naumann-Bartsch N, De Moerloose B, Osborn M, Schultz KR, Sedlacek P, Giona F, Zwaan CM, Shimada H, Versluijs B, Millot F, Hijiya N, Suttorp M, Metzler M. Management of children and adolescents with chronic myeloid leukemia in blast phase: International pediatric CML expert panel recommendations. Leukemia. 2023;37(3):505–17. https://doi.org/10.1038/s41375-023-01822-2 DOI: https://doi.org/10.1038/s41375-023-01822-2
17. Athale U, Hijiya N, Patterson BC, Bergsagel J, Andolina JR, Bittencourt H, Schultz KR, Burke MJ, Redell MS, Kolb EA, Johnston DL. Management of chronic myeloid leukemia in children and adolescents: Recommendations from the Children’s Oncology Group CML Working Group. Pediatr Blood Cancer. 2019;66(9):e27827. https://doi.org/10.1002/pbc.27827 DOI: https://doi.org/10.1002/pbc.27827
18. Zhao Y, Wang J, Luo Y, Shi J, Zheng W, Tan Y, Cai Z, Huang H. Reduced-intensity allogeneic hematopoietic stem cell transplantation combined with imatinib has comparable event-free survival and overall survival to long-term imatinib treatment in young patients with chronic myeloid leukemia. Ann Hematol. 2017;96(8):1353–60. https://doi.org/10.1007/s00277-017-3021-y DOI: https://doi.org/10.1007/s00277-017-3021-y
19. Craddock CF. We do still transplant CML, don’t we? Hematology Am Soc Hematol Educ Program. 2018;2018(1):177–84. https://doi.org/10.1182/asheducation-2018.1.177 DOI: https://doi.org/10.1182/asheducation-2018.1.177
20. Copelan EA, Avalos BR, Ahn KW, Zhu X, Gale RP, Grunwald MR, Hamadani M, Hamilton BK, Hale GA, Marks DI, Waller EK, Savani BN, Costa LJ, Ramanathan M, Cahn JY, Khoury HJ, Weisdorf DJ, Inamoto Y, Kamble RT, Schouten HC, Wirk B, Litzow MR, Aljurf MD, van Besien KW, Ustun C, Bolwell BJ, Bredeson CN, Fasan O, Ghosh N, Horowitz MM, Arora M, Szer J, Loren AW, Alyea EP, Cortes J, Maziarz RT, Kalaycio ME, Saber W. Comparison of outcomes of allogeneic transplantation for chronic myeloid leukemia with cyclophosphamide in combination with intravenous busulfan, oral busulfan, or total body irradiation. Biol Blood Marrow Transplant. 2015;21(3):552–8. https://doi.org/10.1016/j.bbmt.2014.12.010 DOI: https://doi.org/10.1016/j.bbmt.2014.12.010
21. Suttorp M, Claviez A, Bader P, Peters C, Gadner H, Ebell W, Dilloo D, Kremens B, Kabisch H, Führer M, Zintl F, Göbel U, Klingebiel T. Allogeneic stem cell transplantation for pediatric and adolescent patients with CML: results from the prospective trial CML-paed I. Klin Padiatr. 2009;221(6):351–7. https://doi.org/10.1055/s-0029-1239529 DOI: https://doi.org/10.1055/s-0029-1239529
22. Pichler H, Sedlacek P, Meisel R, Beier R, Faraci M, Kalwak K, Ifversen M, Müller I, Stein J, Vettenranta K, Kropshofer G, Kolenova A, Karlhuber S, Glogova E, Poetschger U, Peters C, Suttorp M, Matthes-Leodolter S, Balduzzi A. Haematopoietic stem cell transplantation after reduced intensity conditioning in children and adolescents with chronic myeloid leukaemia: A prospective multicentre trial of the I-BFM Study Group. Br J Haematol. 2024;205(1):268–79. https://doi.org/10.1111/bjh.19535 DOI: https://doi.org/10.1111/bjh.19535
23. Berger M, Lanino E, Cesaro S, Zecca M, Vassallo E, Faraci M, De Bortoli M, Barat V, Prete A, Fagioli F. Feasibility and outcome of haploidentical hematopoietic stem cell transplantation with post-transplant high-dose cyclophosphamide for children and adolescents with hematologic malignancies: an AIEOPGITMO Retrospective Multicenter Study. Biol Blood Marrow Transplant. 2016;22(5):902–9. https://doi.org/10.1016/j.bbmt.2016.02.002 DOI: https://doi.org/10.1016/j.bbmt.2016.02.002
24. Millot F, Ampatzidou M, Moulik NR, Tewari S, Elhaddad A, Hammad M, Pichler H, Lion T, Tragiannidis A, Shima H, An W, Yang W, Karow A, Farah R, Luesink M, Dworzak M, Sembill S, De Moerloose B, Sedlacek P, Schultz KR, Kalwak K, Versluys B, Athale U, Hijiya N, Metzler M, Suttorp M. Management of children and adolescents with chronic myeloid leukemia in chronic phase: International pediatric chronic myeloid leukemia expert panel recommendations. Leukemia. 2025;39(4):779–91. https://doi.org/10.1038/s41375-025-02543-4 DOI: https://doi.org/10.1038/s41375-025-02543-4
25. Millot F, Suttorp M, Ragot S, Leverger G, Dalle JH, Thomas C, Cheikh N, Nelken B, Poirée M, Plat G, Versluys B, Lausen B, Borisevich M. Discontinuation of imatinib in children with chronic myeloid leukemia: a study from the International Registry of Childhood CML. Cancers (Basel). 2021;13(16):4102. https://doi.org/10.3390/cancers13164102 DOI: https://doi.org/10.3390/cancers13164102
26. Chalandon Y, Saruerda A, Corbacioglu S, Greco R, Kroger N, Carreras E. Chronic myeloid leukemia. In: The EBMT Handbook. Europe: EBMT; 2024. p. 771–6.
27. Schmidt S, Liu Y, Hu ZH, Williams KM, Lazarus HM, Vij R, Kharfan-Dabaja MA, Ortí G, Wiernik PH, Weisdorf D, Kamble RT, Herzig R, Wirk B, Cerny J, Bacher U, Chaudhri NA, Nathan S, Farhadfar N, Aljurf M, Gergis U, Szer J, Seo S, Hsu JW, Olsson RF, Maharaj D, George B, Hildebrandt GC, Agrawal V, Nishihori T, Abdel-Azim H, Alyea E, Popat U, Sobecks R, Scott BL, Holter Chakrabarty J, Saber W. The role of donor lymphocyte infusion (DLI) in posthematopoietic cell transplant (HCT) relapse for chronic myeloid leukemia (CML) in the tyrosine kinase inhibitor (TKI) era. Biol Blood Marrow Transplant. 2020;26(6):1137–43. https://doi.org/10.1016/j.bbmt.2020.02.006 DOI: https://doi.org/10.1016/j.bbmt.2020.02.006
28. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: chronic myeloid leukemia. Version 3. NCCN; 2025.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Roseane Vasconcelos Gouveia, Mariana Bohns Michalowski, Paulo Henrique dos Santos Klinger, Luciana dos Santos Domingues, Ana Carolina Ribeiro Correa, Mariane Farherr Caleffi , Antonio Vaz de Macedo
This work is licensed under a Creative Commons Attribution 4.0 International License.
