Real-World Experience of Treating Pediatric Chronic Myeloid Leukemia: Retrospective Study from a Cancer Center in Southern India

Abstract

Introduction Chronic myeloid leukemia (CML) is rare in children and constitutes 2% of all leukemia. We present our institute experience in treating pediatric CML for 20 years.

Objectives There is a paucity of data on pediatric CML from India, hence we would like to present treatment responses and survival rates in our pediatric population treated with tyrosine kinase inhibitors at our center.

Materials and Methods Patients aged less than 18 years, diagnosed with CML from 2000 to 2019, and treated with imatinib were analyzed retrospectively considering demographic features, treatment characteristics, and survival outcomes. Descriptive analysis was done for the baseline characteristics. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method and the factors were compared using the log-rank test.

Results During the study period, 95 patients were diagnosed with CML of which 54 (56.8%) were males. The most common stage at presentation was the chronic phase (CP) with 84 (88.4%) patients followed by accelerated phase (AP) and blast crisis (BC) with 6 (6.3%) and 5 (5.3%) patients respectively. The median duration of follow-up for all patients was 98 months. EFS and OS at 8 years for patients with CML-CP were 43.1% and 80.4% respectively. Complete hematological response, complete cytogenetic response, and major molecular response was documented in 91 (95.7%), 73 (76.8%), and 63 (66.3%) patients respectively.

Conclusion Outcomes in pediatric CML are comparable to that of adults. Imatinib is well tolerated in children.

Keywords

pediatric - chronic myeloid leukemia - imatinib - responses - survival outcomes

• References

• 1 Ries LAG, Smith MA, Gurney JG. et al. Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975–1995, National Cancer Institute, SEER Program. NIH Pub. No. 99–4649. Bethesda, MD, 1999
• 2 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 (04) 392-399
• 3 Dikshit RP, Nagrani R, Yeole B, Koyande S, Banawali S. Changing trends of chronic myeloid leukemia in greater Mumbai, India over a period of 30 years. Indian J Med Paediatr Oncol 2011; 32 (02) 96-100
• 4 Pushpam D, Bakhshi S. Paediatric chronic myeloid leukaemia: is it really a different disease?. Indian J Med Res 2019; 149 (05) 600-609
• 5 Andolina JR, Neudorf SM, Corey SJ. How I treat childhood CML. Blood 2012; 119 (08) 1821-1830
• 6 Suttorp M, Schulze P, Glauche I. et al. Front-line imatinib treatment in children and adolescents with chronic myeloid leukemia: results from a phase III trial. Leukemia 2018; 32 (07) 1657-1669
• 7 Martinet D, Mühlematter D, Jotterand Bellomo M. [Fluorescent in-situ hybridization technique (FISH) in the diagnosis of Philadelphia translocation in chronic myeloid leukemia]. Schweiz Med Wochenschr 1996; 126 (20) 855-863
• 8 Wells SJ, Phillips CN, Winton EF, Farhi DC. Reverse transcriptase-polymerase chain reaction for bcr/abl fusion in chronic myelogenous leukemia. Am J Clin Pathol 1996; 105 (06) 756-760
• 9 Arber DA, Orazi A, Hasserjian R. et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127 (20) 2391-2405
• 10 Millot F, Guilhot J, Nelken B. et al. Imatinib mesylate is effective in children with chronic myelogenous leukemia in late chronic and advanced phase and in relapse after stem cell transplantation. Leukemia 2006; 20 (02) 187-192
• 11 Suttorp M, Millot F. Treatment of pediatric chronic myeloid leukemia in the year 2010: use of tyrosine kinase inhibitors and stem-cell transplantation. Hematology (Am Soc Hematol Educ Program) 2010; 2010: 368-376
• 12 Baccarani M, Saglio G, Goldman J. et al; European LeukemiaNet. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006; 108 (06) 1809-1820
• 13 Baccarani M, Cortes J, Pane F. et al; European LeukemiaNet. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009; 27 (35) 6041-6051
• 14 Baccarani M, Deininger MW, Rosti G. et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013; 122 (06) 872-884
• 15 Testoni N, Marzocchi G, Luatti S. et al. Chronic myeloid leukemia: a prospective comparison of interphase fluorescence in situ hybridization and chromosome banding analysis for the definition of complete cytogenetic response: a study of the GIMEMA CML WP. Blood 2009; 114 (24) 4939-4943
• 16 Hughes T, Deininger M, Hochhaus A. 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 (01) 28-37
• 17 Cross NCP, White HE, Müller MC, Saglio G, Hochhaus A. Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia 2012; 26 (10) 2172-2175
• 18 Müller MC, Cross NCP, Erben P. et al. Harmonization of molecular monitoring of CML therapy in Europe. Leukemia 2009; 23 (11) 1957-1963
• 19 Glivec ® International Patient Assistance Program (GIPAP). http://www.themaxfoundation.org/gipap/Default.aspx . Accessed December 8, 2021
• 20 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 (07) e437-e444
• 21 Millot F, Suttorp M, Guilhot J. et al. The International Registry for Chronic Myeloid Leukemia (CML) in Children and Adolescents (I-CML-Ped-Study): objectives and preliminary results. Blood 2012; 120: 3741
• 22 Mitra D, Trask PC, Iyer S, Candrilli SD, Kaye JA. Patient characteristics and treatment patterns in chronic myeloid leukemia: evidence from a multi-country retrospective medical record chart review study. Int J Hematol 2012; 95 (03) 263-273
• 23 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 (09) 1009-1012
• 24 Ganta RR, Nasaka S, Linga VG, Gundeti S, Maddali LS, Digumarti RR. Effectiveness of three prognostic scoring systems in predicting the response and outcome in pediatric chronic myeloid leukemia chronic phase on frontline imatinib. Indian J Med Paediatr Oncol 2017; 38 (03) 282-286
• 25 Linga VG, Ganta RR, Kalpathi KI. et al. Response to imatinib mesylate in childhood chronic myeloid leukemia in chronic phase. South Asian J Cancer 2014; 3 (04) 203-205
• 26 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 (01) 110-115
• 27 Chandra D, Singh J, Deka R. et al. The biology of chronic myelogenous leukemia in childhood and young adolescents: an Indian perspective. Indian J Med Paediatr Oncol 2018; 39: 142-145
• 28 Parikh SK, Anand A, Panchal H. et al; Department of Medical and Pediatric Oncology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat. INDIA. A retrospective study of clinical profile and long term outcome to imatinib mesylate alone in childhood chronic myeloid leukemia in chronic phase. Gulf J Oncolog 2017; 1 (23) 15-20
• 29 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 (08) 1363-1371
• 30 Giona F, Mariani S, Gnessi L. et al. Bone metabolism, growth rate and pubertal development in children with chronic myeloid leukemia treated with imatinib during puberty. Haematologica 2013; 98 (03) e25-e27
• 31 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 (03) 481-484
• 32 de la Fuente J, Baruchel A, Biondi A. et al; International BFM Group (iBFM) Study Group Chronic Myeloid Leukaemia Committee. 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 (01) 33-47
• 33 Etienne G, Guilhot J, Rea D. et al. Long-term follow-up of the French Stop Imatinib (STIM1) Study in patients with chronic myeloid leukemia. J Clin Oncol 2017; 35 (03) 298-305
• 34 Smeding C, Szydło A, Pieluszczak K, Grzeszkiewicz K, Pawelec K. Efficacy and safety of imatinib in paediatric CML - a single centre study. In Vivo 2019; 33 (03) 869-875