Abstract
Chronic myeloid leukemia (CML) is a rare disease among children. A retrospective study was conducted from November 2002 to March 2019 at a single institution in China. A total of 36 pediatric CML patients (25 male and 11 female) were enrolled. Median follow-up time was 51 months (range 8–144), and 5-year overall survival and event-free survival were 95.5 ± 4.4% and 88.9 ± 6.0%, respectively. Among the 25 patients whose response to imatinib mesylate (IM) was regularly monitored, 92.0% achieved complete hematologic response at 3 months, 80.0% achieved complete cytogenetic response at 12 months, and 64.0% achieved major molecular response at 18 months after IM therapy. A higher WBC count at diagnosis was associated with failure to achieve early molecular response (EMR). Height standard deviation score after long-term treatment was significantly and positively correlated with age at diagnosis and at the start of IM therapy. Overall, IM therapy was effective in treating pediatric CML, and WBC count at diagnosis might be an ideal predictor of EMR. Moreover, retardation of height and weight growth due to IM tended to affect patients younger than 9 years old at diagnosis, and longitudinal growth might normalize further into treatment.
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References
Millot F, Traore P, Guilhot J, Nelken B, Leblanc T, Leverger G, et al. Clinical and biological features at diagnosis in 40 children with chronic myeloid leukemia. Pediatrics. 2005;116:140–3.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.
Hijiya N, Millot F, Suttorp M. Chronic myeloid leukemia in children: clinical findings, management, and unanswered questions. Pediatr Clin N Am. 2015;62:107–19.
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.
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. Leukemia Lymphoma. 2012;53:2430–3.
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.
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.
Andolina JR, Neudorf SM, Corey SJ. How I treat childhood CML. Blood. 2012;119:1821–30.
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.
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.
Millot F, Guilhot J, Baruchel A, Petit A, Leblanc T, Bertrand Y, et al. Growth deceleration in children treated with imatinib for chronic myeloid leukaemia. Eur J Cancer. 2014;50:3206–11.
Shima H, Tokuyama M, Tanizawa A, Tono C, Hamamoto K, Muramatsu H, et al. Distinct impact of imatinib on growth at prepubertal and pubertal ages of children with chronic myeloid leukemia. J Pediatr. 2011;159:676–81.
Samis J, Lee P, Zimmerman D, Suttorp M, Hijiya N. The complexity of growth failure in children receiving tyrosine kinase inhibitor therapy for chronic myelogenous leukemia. Pediatr Blood Cancer. 2017;64. https://doi.org/10.1002/pbc.26703
Mahon F-X, Réa D, Guilhot J, Guilhot F, Huguet F, Nicolini F, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11:1029–35.
Saussele S, Richter J, Guilhot J, Gruber FX, Hjorth-Hansen H, Almeida A, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19:747–57.
Radich JP, Deininger M, Abboud CN, Altman JK, Berman E, Bhatia R, et al. Chronic myeloid leukemia, version 1. 2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2018;16:1108–35.
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.
Zong XN, Li H. Construction of a new growth references for China based on urban Chinese children: comparison with the WHO growth standards. PLoS ONE. 2013;8:e59569.
Kong XL, Xiao SP, Huang XH, et al. Quantitative analysis of height and weight in children with beta-thalassemia major and the associated factor [J]. Chin J Child Health Care. 2018;26(6):622–5.
Gore L, Kearns PR, de Martino ML, Lee N, De Souza CA, Bertrand Y, et al. Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase: results from a phase II trial. J Clin Oncol. 2018;36:1330–8.
Hijiya N, Suttorp M. How I treat chronic myeloid leukemia in children and adolescents. Blood. 2019;133:2374–84.
Tanizawa A. Optimal management for pediatric chronic myeloid leukemia. Pediatr Int. 2016;58:171–9.
Chen Y, Wang H, Kantarjian H, Cortes J. Trends in chronic myeloid leukemia incidence and survival in the United States from 1975 to 2009. Leuk Lymphoma. 2013;54:1411–7.
Shi YM, Liu S. Sex ratio at birth in China: changes and implications [J]. Popul Res. 2015;39:35–48.
Cwynarski K, Roberts IAG, Iacobelli S, van Biezen A, Brand R, Devergie A, et al. Stem cell transplantation for chronic myeloid leukemia in children. Blood. 2003;102:1224–31.
Pavlovsky C, Kantarjian H, Cortes JE. First-line therapy for chronic myeloid leukemia: past, present, and future. Am J Hematol. 2009;84:287–93.
Karalexi MA, Baka M, Ryzhov A, Zborovskaya A, Dimitrova N, Zivkovic S, et al. Survival trends in childhood chronic myeloid leukaemia in Southern-Eastern Europe and the United States of America. Eur J Cancer Oxf Engl. 1990;2016(67):183–90.
El-Alfy MS, Al-Haddad AM, Hamed AA. Management of CML in the pediatric age group: imatinib mesylate or SCT. J Egypt Natl Canc Inst. 2010;22:227–32.
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.
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.
Giona F, Saglio G, Santopietro M, Menna G, Putti MC, Micalizzi C, et al. Early response does not predict outcome in children and adolescents with chronic myeloid leukaemia treated with high-dose imatinib. Br J Haematol. 2018;180:895–8.
Nievergall E, Reynolds J, Kok CH, Watkins DB, Biondo M, Busfield SJ, et al. TGF-α and IL-6 plasma levels selectively identify CML patients who fail to achieve an early molecular response or progress in the first year of therapy. Leukemia. 2016;30:1263–72.
Kok CH, Yeung DT, Lu L, Watkins DB, Leclercq TM, Dang P, et al. Gene expression signature that predicts early molecular response failure in chronic-phase CML patients on frontline imatinib. Blood Adv. 2019;3:1610–21.
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.
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.
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.
Samis J, Lee P, Zimmerman D, Arceci RJ, Suttorp M, Hijiya N. Recognizing endocrinopathies associated with tyrosine kinase inhibitor therapy in children with chronic myelogenous leukemia. Pediatr Blood Cancer. 2016;63:1332–8.
Carroll M, Ohno-Jones S, Tamura S, Buchdunger E, Zimmermann J, Lydon NB, et al. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood. 1997;90:4947–52.
Narayanan KR, Bansal D, Walia R, Sachdeva N, Bhansali A, Varma N, et al. Growth failure in children with chronic myeloid leukemia receiving imatinib is due to disruption of GH/IGF-1 axis. Pediatr Blood Cancer. 2013;60:1148–53.
Bansal D, Shava U, Varma N, Trehan A, Marwaha RK. Imatinib has adverse effect on growth in children with chronic myeloid leukemia. Pediatr Blood Cancer. 2012;59:481–4.
Rastogi MV, Stork L, Druker B, Blasdel C, Nguyen T, Boston BA. Imatinib mesylate causes growth deceleration in pediatric patients with chronic myelogenous leukemia. Pediatr Blood Cancer. 2012;59:840–5.
Giona F, Mariani S, Gnessi L, Moleti ML, Rea M, De Vellis A, et al. Bone metabolism, growth rate and pubertal development in children with chronic myeloid leukemia treated with imatinib during puberty. Haematologica. 2013;98:e25-27.
de Bruijn CMA, Millot F, Suttorp M, Borisevich M, Brons P, Lausen B, et al. Discontinuation of imatinib in children with chronic myeloid leukaemia in sustained deep molecular remission: results of the STOP IMAPED study. Br J Haematol. 2019;185:718–24.
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Cai, Y., Liu, C., Guo, 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 113, 413–421 (2021). https://doi.org/10.1007/s12185-020-03042-1
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DOI: https://doi.org/10.1007/s12185-020-03042-1