Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
Journal Citation Indicator (JCI) (2023) – 0.4
Scopus CiteScore – 3.7 (CiteScore Tracker – 4.0)
Index Copernicus  – 171.00; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 1, January, p. 91–98

doi: 10.17219/acem/66462

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

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

Małgorzata Janeczko-Czarnecka1,A,B,C,D, Maryna Krawczuk-Rybak2,B, Irena Karpińska-Derda3,B, Maciej Niedźwiecki4,B, Katarzyna Musioł5,B, Magdalena Ćwiklińska6,B, Katarzyna Drabko7,B, Katarzyna Mycko8,B, Tomasz Ociepa9,B, Katarzyna Pawelec10,B, Danuta Januszkiewicz-Lewandowska11,B, Marek Ussowicz1,B,E,F, Blanka Rybka1,B, Renata Ryczan-Krawczyk1,B, Andrzej Kołtan12,B, Grażyna Karolczyk13,B, Agnieszka Zaucha-Prażmo7,B, Wanda Badowska14,B, Krzysztof Kałwak1,A,E,F

1 Department and Clinic of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Poland

2 Department of Pediatric Oncology and Hematology, Medical University of Bialystok, Poland

3 Department of Pediatrics, Hematology and Oncology, Dr Edward Hanke Chorzów Center of Pediatrics and Oncology, Poland

4 Department and Clinic of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, Poland

5 Silesian Children's Health Center, Department of Oncology, Hematology and Pediatric Chemotherapy, Medical University of Silesia in Katowice, Poland

6 Department of Oncology and Hematology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Kraków, Poland

7 Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Poland

8 Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland

9 Department of Pediatrics, Pediatric Hematology and Oncology, Pomeranian Medical University in Szczecin, Poland

10 Department and Clinic of Pediatrics, Hematology and Oncology, Medical University of Warsaw, Poland

11 Department of Oncology, Hematology and Pediatric Transplantatology, Poznan University of Medical Sciences, Poland

12 Department of Pediatrics, Hematology and Oncology, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Poland

13 Department of Hematooncology, Wladyslaw Buszkowski Provincial Specialist Children's Hospital in Kielce, Poland

14 Department and Clinic of Pediatric Hematology and Oncology, Prof. Stanisław Popowski Provincial Specialist Childrens’ Hospital in Olsztyn, Poland

Abstract

Background. Chronic myeloid leukemia (CML) constitutes only 2–3% of all leukemias in pediatric patients. Philapelphia chromosome and BCR-ABL fusion are genetic hallmarks of CML, and their presence is crucial for targeted molecular therapy with tyrosine kinase inhibitors (TKIs), which replaced hematopoietic stem cell transplantation (HSCT) as a standard first-line therapy. The disease in pediatric population is rare, and despite molecular and clinical similarities to CML in adults, different approach is needed, due to the long lifetime expectancy and distinct developmental characteristics of affected children.
Objectives. The objective of this study is to evaluate treatment with imatinib in Polish pediatric patients with CML.
Material and Methods. We analyzed the results of treatment with imatinib in 57 pediatric patients (June 2006 – January 2016) from 14 Polish pediatric hematology and oncology centers.
Results. In the study group, 40 patients continued imatinib (median follow-up: 23.4 months), while in 17 the treatment was terminated (median follow-up: 15.1 months) due to therapy failure. In the latter group, 13 patients underwent HSCT, while 4 switched to second-generation TKIs. The 5-year overall survival rate (OS) in the study group was 96%, and the 5-year event-free survival (EFS) was 81%.
Conclusion. Our results confirm that the introduction of TKI therapy has revolutionized the treatment of CML in the pediatric population by replacing the previous method of treatment with HSCT and allowing a high percentage of OS and EFS.

Key words

children, imatinib, adolescents, chronic myeloid leukemia

References (27)

  1. Millot F, Traore P, Guilhot J, et al. Clinical and biological features at diagnosis in 40 children with chronic myeloid leukemia. Pediatrics. 2005;116(1):140–143.
  2. 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;1:368–376.
  3. Andolina JR, Neudorf SM, Corey SJ. How I treat childhood CML. Blood. 2012;119(8):1821–1830.
  4. Millot F, Esperou H, Bordigoni P, et al. 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 Transplant. 2003;32(10):993–999.
  5. Cwynarski K, Roberts IA, Iacobelli S, et al. Stem cell transplantation for chronic myeloid leukemia in children. Blood. 2003;102(4):1224–1233.
  6. Muramatsu H, Kojima S, Yoshimi A, et al. Outcome of 125 children with chronic myelogenous leukemia who received transplants from unrelated donors: The Japan Marrow Donor Program. Biol Blood Marrow Transplant. 2010;16:231–238.
  7. Zecca 1, Prete A, Rondelli R, et al. Chronic graft-versus-host disease in children: Incidence, risk factors, and impact on outcome. Blood. 2002;100(4):1192–1200.
  8. Champagne MA, Capdeville R, Krailo M, et al. Imatinib mesylate (STI571) for treatment of children with Philadelphia chromosome-positive leukemia: Results from a Children’s Oncology Group phase 1 study. Blood. 2004;104(9):2655–2660.
  9. 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(2):187–192.
  10. Millot F, Baruchel A, Guilhot J, et al. Imatinib is efficient but has a negative impact on growth in children with previously untreated chronic myelogenous leukaemia (CML) in early chronic phase (CP): Results of the French national phase IV trial. Blood. 2009;110:863.
  11. Suttorp M, Thiede C, Tauer, et al. Chronic myeloid leukemia in pediatrics: First results from study CML-PAED II. Blood. 2009;114:145.
  12. Millot F, Guilhot J, Suttorp M, et al. The experience of the International Registry for Chronic Myeloid Leukemia (CML) in Children and Adolescents (I-CML-Ped Study): Prognostic consideration. [Abstract, Oral Presentation No. 521] Session 632: Chronic myeloid leukemia: Prognosis and therapy.
  13. Schmid H, Jaeger BA, Lohse J, et al. Longitudinal growth retardation in a prepuberal girl with chronic myeloid leukemia on long-term treatment with imatinib. Haematologica. 2009;94(8):1177–1179.
  14. Kolb EA, Pan Q, Ladanyi M, et al. Imatinib mesylate in Philadelphia chromosome-positive leukemia in childhood. Cancer. 2003;98:2643–2650.
  15. Millot F, Baruchel A, Guilhot J, 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(20):2827–2832.
  16. Kerkela R, Grazette L, Yacobi R, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2006;12(8):908–916.
  17. Millot F, Guilhot J, Baruchel A, et al. Growth deceleration in children treated with imatinib for chronic myeloid leukaemia. Eur J Cancer. 2014;50(18):3206–3211.
  18. Jaeger BA, Tauer JT, Ulmer A, et al. Changes in bone metabolic parameters in children with chronic myeloid leukemia on imatinib treatment. Med Sci Monit. 2012;18(12):CR721–728.
  19. Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362(24):2260–2270.
  20. Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251–2259.
  21. Soverini S, Iacobucci I, Baccarani M, et al. Targeted therapy and the T315I mutation in Philadelphia-positive leukemias. Haematologica. 2007;92(4):437–439.
  22. Aplenc R, Blaney SM, Strauss LC, et al. Pediatric phase I trial and pharmacokinetic study of dasatinib: A report from the Children’s Oncology Group phase I consortium. J Clin Oncol. 2011;29(7):839–844.
  23. Zwaan CM, Rizzari C, Mechinaud F, et al. Dasatinib in children and adolescents with relapsed or refractory leukemia: Results of the CA180–018 phase I dose-escalation study of the innovative therapies for children with cancer consortium. J Clin Oncol. 2013;31(19):2460–2468.
  24. Marangon E, Citterio M, Sala F, et al. Pharmacokinetic profile of imatinib mesylate and N-desmethyl-imatinib (CGP 74588) in children with newly diagnosed Ph(+) acute leukemias. Cancer Chemother Pharmacol. 2009;63:563–566.
  25. Picard S, Titier K, Etienne G, et al. Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2007;109:3496–3499.
  26. Mauro MJ, Deininger MW. Management of drug toxicities in chronic myeloid leukaemia. Best Pract Res Clin Haematol. 2009;22:409–429.
  27. Millot F, Claviez A, Leverger G, et al. Imatinib cessation in children and adolescents with chronic myeloid leukemia in chronic phase. Pediatr Blood Cancer. 2014;61(2):355–357.
© Wroclaw Medical University