Skip to main content

Advertisement

Log in

Can prognostic scoring systems for chronic myeloid leukemia as established in adults be applied to pediatric patients?

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

In contrast to adult medicine, specific scoring systems predicting the treatment response for an individual pediatric patient (pt) with chronic myeloid leukemia (CML) have not yet been defined. We evaluated to what extend prognostic scores as described for adults (e.g., Sokal, Hasford, EUTOS score) resulted in comparable risk group categorizations in a pediatric cohort. Parameters for score calculation were extracted from a data set of 90 patients enrolled into trial CML-PAED-II and treated by a standard dose of imatinib. At month 3 and at month 6, treatment response was analyzed based on the transcript ratio BCR-ABL1/ABL1. By the EUTOS, Hasford, and Sokal scores 81, 59, and 62 % of the patients were categorized as low risk, respectively; 19, 14, and 16 % of the patients as high risk, respectively; and by Hasford and Sokal scores 27 and 22 % of the patients, respectively, as intermediate risk. Twenty-seven out of 72 patients analyzable (38 %) exhibited a transcript ratio >10 % at month 3. We show that only the EUTOS score, but not the Sokal and Hasford score, correlates with this early outcome (p = 0.008). Analyzing the EUTOS score separately, we can demonstrate that lowering the cutoff from 87 to 48 points for categorization in low- and high-risk individuals increases the odds ratio from 2.4 (95 % CI 0.6 to 10.4) to 3.6 (95 % CI 1.3 to 10.9). Data are provided on the distribution of risk categories and resulting discrepancies when adult scores are applied on children and adolescents with CML at diagnosis. A larger number of patients and longer follow-up are still needed to develop a prognostic score specifically adapted to the pediatric and adolescent age cohorts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Altman AJ (2000) Chronic leukemias of childhood. In: Pizzo PA, Poplack DG (eds) Principles and practice of pediatric oncology. Lippincot Williams & Wilkins (LWW) pp 591-614

  2. Andolina JR, Neudorf SM, Corey SJ (2012) How I treat childhood CML. Blood 119(8):1821–1830

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Baccarani M (2010) Calculation of relative risk of CML patients http://www.leukemia-net.org/content/leukemias/cml/cml_score/index_eng.html

  4. Baccarani M, Pileri S, Steegmann JL et al (2012) Chronic myeloid leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(S7):72–77

    Google Scholar 

  5. Breccia M, Finsinger P, Loglisci G et al (2012) The EUTOS score identifies chronic myeloid leukemia patients treated with imatinib first or second line. Leuk Res 36(9):e209–e210

    Article  PubMed  Google Scholar 

  6. Castagneti F, Gugliotta G, Palandri F et al (2012) EUTOS score is predictive for survival and outcome of patients with early chronic phase chronic myeloid leukemia treated with nilotinib-base regimens. Haematologica 97(Suppl. 1, abstract #193):76

  7. Castro-Malaspina H, Schaison G, Breire J et al (1983) Philadelphia chromosome-positive chronic myelocytic leukemia in children. Survival and prognostic factors. Cancer 52(4):721–727

    Article  CAS  PubMed  Google Scholar 

  8. Cerrano M, Crisà E, Pregno P et al (2013) Excellent therapeutic results achieved in chronic myeloid leukemia patients with front-line imatinib and early treatment modifications in suboptimal responders: a retrospective study on 91 unselected patients. Am J Hematol 88(10):838–842

    CAS  PubMed  Google Scholar 

  9. Cortes J, Kantarjian H (2003) Advanced-phase chronic myeloid leukemia. Semin Hematol 40(1):79–86

    Article  PubMed  Google Scholar 

  10. Cwynarski K, Roberts IA, Iacobelli S et al (2003) Stem cell transplantation for chronic myeloid leukemia in children. Blood 102(4):1224–1231

    Article  CAS  PubMed  Google Scholar 

  11. De la Fuente J, Baruchel A, Biondi A, on behalf of the International BFM Group Study Group Chronic Myeloid Leukaemia Committee et al (2014) How I manage CML in children. Guidelines for the management of chronic myeloid leukaemia in children and young people up to the age of 18 years. Br J Haematol 167(1):33–47

    Article  PubMed  Google Scholar 

  12. Druker BJ, Guilhot F, O’Brien SG et al (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355(23):2408–2417

    Article  CAS  PubMed  Google Scholar 

  13. Faderl S, Talpaz M, Estrov Z et al (1999) The biology of chronic myeloid leukemia. N Engl J Med 341(3):164–172

    Article  CAS  PubMed  Google Scholar 

  14. Giles FJ, Coutre PD, Pinilla-Ibarz J et al (2013) Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow, results of a phase II study. Leukemia 27(1):107–112

    Article  CAS  PubMed  Google Scholar 

  15. Goldman JM (2007) How I treat chronic myeloid leukemia in the imatinib era. Blood 110(8):2828–2837

    Article  CAS  PubMed  Google Scholar 

  16. Goldman JM, Majhail NS, Klein JP et al (2010) Relapse and late mortality in 5-year survivors of myeloablative allogeneic hematopoietic cell transplantation for chronic myeloid leukemia in first chronic phase. J Clin Oncol 28(11):1888–1895

    Article  PubMed Central  PubMed  Google Scholar 

  17. Gratwohl A, Brand R, Apperley J et al (2006) Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: transplant activity, long-term data and current results. An analysis by the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EMBT). Haematologica 91(4):513–521

    PubMed  Google Scholar 

  18. Gugliotta G, Castagnetti F, Palandri F et al (2011) Frontline imatinib treatment of chronic myeloid leukemia: no impact of age on outcome, a survey by the GIMEMA CML Working Party. Blood 117(21):5591–5599

    Article  CAS  PubMed  Google Scholar 

  19. Hanfstein B, Müller MC, Hehlmann R et al (2012) Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia 26(9):2096–2102

    Article  CAS  PubMed  Google Scholar 

  20. Hasford J, Pfirmann M, Hehlman R et al (1998) A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alpha. Writing Committee for the collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst 90(11):850–858

    Article  CAS  PubMed  Google Scholar 

  21. Hasford J, Baccarani M, Hoffman V et al (2011) Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 118(3):686–692

    Article  CAS  PubMed  Google Scholar 

  22. Hijiya N, Millot F, Suttorp M (2015) Chronic myeloid leukemia in children: clinical findings, management, and unanswered questions. Pediatr Clin N Am 62:107–119

    Article  Google Scholar 

  23. Hochhaus A (2008) Prognostic factors in chronic myeloid leukemia (CML). Onkologie 31(11):576–578

    Article  PubMed  Google Scholar 

  24. Hochhaus A (2011) Educational session: managing chronic myeloid leukemia as a chronic disease. Hematol Am Soc Hematol Educ Program 2011:128–135

    Article  Google Scholar 

  25. Hochhaus A, O’Brien SG, Guilhot F et al (2009) Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 23(6):1054–1061

    Article  CAS  PubMed  Google Scholar 

  26. Hoffman VS, Baccarani M, Lindoerfer D et al (2013) The EUTOS prognostic score: review and validation in 1288 patients with CML treated frontline with imatinib. Leukemia 27(10):2016–2022

    Article  Google Scholar 

  27. Hughes T, Hochhaus A, Brandford S et al (2010) Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood 116(19):3758–3765

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Jabbour E, Cortes J, Kantarjian MH et al (2006) Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failure. Blood 108(4):1421–1423

    Article  CAS  PubMed  Google Scholar 

  29. Jabbour E, Cortes J, Nazha A et al (2012) EUTOS score is not predictive for survival and outcome in patients with early chronic phase of chronic myeloid leukemia treated with tyrosine kinase inhibitors: a single institution experience. Blood 119(19):4524–4526

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Kalmanti L, Saussele S, Lauseker M et al (2014) Younger patients with chronic myeloid leukemia do well in spite of poor prognostic indicators: results from the randomized CML-study IV. Ann Hematol 93(1):71–80

    Article  PubMed Central  PubMed  Google Scholar 

  31. Lakshmaiah KC, Bhise R, Purohit S et al (2012) Chronic myeloid leukemia in children and adolescents: results of treatment with imatinib mesylate. Leuk Lymphoma 53(12):2430–2433

    Article  CAS  PubMed  Google Scholar 

  32. Latagliata R, Isidori A, Breccia M et al (2013) Complete clearance of Ph + metaphases after 3 months is a very early indicator of good response to imatinib as front-line treatment in chronic myelogenous leukemia. Acta Haematol 129(2):126–134

    Article  CAS  PubMed  Google Scholar 

  33. Marin D, Ibrahim AR, Goldman JM (2011) European Treatment and Outcome Study (EUTOS) score for chronic myeloid leukemia still requires more confirmation. J Clin Oncol 29(29):3944–3945

    Article  PubMed  Google Scholar 

  34. Marin D, Ibrahim AR, Lucas C et al (2012) Assessment of BRC-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 30(3):232–238

    Article  CAS  PubMed  Google Scholar 

  35. Millot F, Traore P, Guilhot J et al (2005) Clinical and biological features at diagnosis in 40 children with chronic myeloid leukemia. Pediatrics 116(140):2004–2473

    Google Scholar 

  36. Millot F, Baruchel A, Guilhot J et al (2011) Imatinib is effective in children with previously treated chronic myeloid leukemia in early chronic phase: results of the French national phase IV trial. J Clin Oncol 29(20):2827–2832

    Article  CAS  PubMed  Google Scholar 

  37. Millot F, Guilhot J, Suttorp M et al (2014) The experience of the international registry for chronic myeloid leukemia (CML) in children and adolescents (I-CML-Ped Study): prognostic consideration. Blood 124 (21), ASH annual meeting abstract #521

  38. Muramatsu H, Kojima S, Yoshimi A et al (2010) Outcome of 125 children with chronic myelogeneous leukemia who received transplants from unrelated donors: the Japan Marrow Donor Program. Biol Blood Marrow Transplant 16(2):231–238

    Article  PubMed  Google Scholar 

  39. National Comprehensive Cancer Network (NCCN) (2013) http://www.nccn.org/patients/guidelines/cml/index.html NCCN practical guidelines in oncology (NCCN Guidelines) (2013). Accessed 13 Sep 2013

  40. Neelakantan P, Gerrard G, Lucas C et al (2013) Combining BCR-ABL1 transcript levels at 3 and 6 months in chronic myeloid leukemia: implications for early intervention strategies. Blood 121(14):2739–2742

    Article  CAS  PubMed  Google Scholar 

  41. O’Reilly RA (1998) Splenomegaly in 2505 patients in a large university medical center from 1913 to 1995. 1913 to 1962: 2056 patients. West J Med 169(2):78–87

    PubMed Central  PubMed  Google Scholar 

  42. Ohm L, Arvidsson I, Barbany G et al (2012) Early landmark analysis of imatinib treatment in CML chronic phase: less than 10 % BCR-ABL by FISH at 3 months associated with improved long-term clinical outcome. Am J Hematol 87(8):760–765

    Article  CAS  PubMed  Google Scholar 

  43. Oyekunle AA, Osho PO, Aneke JC et al (2012) The predictive value of the Sokal and Hasford scoring systems in chronic myeloid leukemia in the imatinib era. J Hematol Malign 2(2):25–32

    Article  Google Scholar 

  44. Pemmaraju N, Kantarjian H, Shan J et al (2012) Analysis of outcomes in adolescents and young adults with chronic myelogenous leukemia treated with upfront tyrosine kinase inhibitor therapy. Haematologica 97(7):1029–1035

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Raman GR, Nasaka S, Gundeti S et al (2014) Effectiveness in predicting response and outcome with three prognostic scoring systems in pediatric CML on upfront imatinib. Blood 124 (21), ASH annual meeting abstract #4549

  46. Saglio G, Fava C (2012) Practical monitoring of chronic myelogenous leukemia: when to change treatment. J Natl Compr Cancer Netw 10(1):121–129

    CAS  Google Scholar 

  47. Sokal JE, Cox EB, Baccarani M et al (1984) Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood 63(4):789–799

    CAS  PubMed  Google Scholar 

  48. Sokal JE, Baccarani M, Tura S et al (1985) Prognostic discrimination among younger patients with chronic granulocytic leukemia: relevance to bone marrow transplantation. Blood 66(6):1352–1357

    CAS  PubMed  Google Scholar 

  49. Sokal JE, Baccarani M, Russo D et al (1988) Staging and prognosis in chronic myelogenous leukemia. Semin Hematol 25(1):49–61

    CAS  PubMed  Google Scholar 

  50. Steegmann JL, Casado LF (2012) The new EUTOS score has prognostic value in the treatment of chronic myeloid leukemia (CML) outside clinical trials. Blood E-Letter published online January 27, 2012

  51. Suttorp M (2006) Protocol for standardized diagnostic procedures, registration and treatment recommendations in children and adolescents with Philadelphia chromosome-positive chronic myeloid leukemia (CML). CML-paed-II Study. http://www.kinderkrebsinfo.de/sites/kinderkrebsinfo/content/e1676/e9032/e1758/e5368/download38391/ClinicalTrialProtocolCML-paed-IIStudyDocumentation,ECVger.pdf (2006). Accessed 13 Sep 2013

  52. Suttorp M, Millot F (2010) Treatment of pediatric chronic myeloid leukemia in the year 2010: use of tyrosine kinase inhibitors and stem cell transplantation. Hematol Am Soc Hematol Edu Program 2010:368–376

    Article  Google Scholar 

  53. Suttorp M, Claviez A, Bader P et al (2009) Allogeneic stem cell transplantation for pediatric and adolescent patients with CML: results from the prospective trial CML-paed-I. Klin Padiatr 221(6):351–357

    Article  CAS  PubMed  Google Scholar 

  54. Suttorp M, Yaniv I, Schultz KR (2011) Controversies in the treatment of CML in children and adolescents. TKIs versus BMT. Biol Blood Marrow Transplant 17(Suppl 1):S115–S122

    Article  PubMed  Google Scholar 

  55. Suttorp M, Eckardt T, Tauer JT et al (2012) Management of chronic myeloid leukemia in childhood. Curr Hematol Malig Rep 7(2):116–124

    Article  PubMed  Google Scholar 

  56. Suttorp M, Glauche I, Gurrea Salas D et al (2013) Scoring systems for predicting outcome of chronic myeloid leukemia in adults are poorly informative in pediatric patients treated with imatinib (abstract). Blood 122(21):2725

    Google Scholar 

  57. Tanaka MF, Kantarjian H, Cortes J et al (2012) Treatment options for chronic myeloid leukemia. Expert Opin Pharmacother 13(6):815–828

    Article  CAS  PubMed  Google Scholar 

  58. Trask PC, Mitra D, Iyer S et al (2012) Patterns and prognostic indicators of response to CML treatment in a multi-country medical record review study. Int J Hematol 95(5):535–544

    Article  PubMed  Google Scholar 

  59. Verbeek W, König H, Boehm J et al (2006) Continuous complete hematological and cytogenetic remission with molecular minimal residual disease 9 years after discontinuation of interferon-alpha in a patient with Philadelphia chromosome-positive chronic myeloid leukemia. Acta Haematol 115(1-2):109–112

    Article  CAS  PubMed  Google Scholar 

  60. Williams K, Thomson D, Seto I et al (2012) Standard 6: age groups for pediatric trials. Pediatrics 129(Suppl 3):S153–S160

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The ongoing support of treating physicians and study nurses participating in CML-PAED trials and in data collection transfer is gratefully acknowledged. The authors thank Christina Nowasz, study nurse of CML-PAED-II, for her valuable assistance. This work was supported financially with an educational grant by Peter-Escher-Foundation for Promotion of Research in Pediatric Hemato-Oncology (Leipzig, Germany). IG was supported by an e:Bio grant of the German Ministry for Research and Education (“MessAge,” BMBF-FKZ 031A315). Results were in part presented as poster at the Meeting of the American Society of Hematology on December 2013 [56].

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Meinolf Suttorp.

Additional information

David Gurrea Salas and Ingmar Glauche contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Table S1

(PDF 737 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gurrea Salas, D., Glauche, I., Tauer, J.T. et al. Can prognostic scoring systems for chronic myeloid leukemia as established in adults be applied to pediatric patients?. Ann Hematol 94, 1363–1371 (2015). https://doi.org/10.1007/s00277-015-2367-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-015-2367-2

Keywords

Navigation