Annals of Hematology

, Volume 94, Issue 8, pp 1363–1371 | Cite as

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

  • David Gurrea Salas
  • Ingmar Glauche
  • Josephine T. Tauer
  • Christian Thiede
  • Meinolf Suttorp
Original Article

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.

Keywords

CML Children Sokal Hasford EUTOS Score 

Notes

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.

Supplementary material

277_2015_2367_MOESM1_ESM.pdf (738 kb)
Table S1 (PDF 737 kb)

References

  1. 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 591-614Google Scholar
  2. 2.
    Andolina JR, Neudorf SM, Corey SJ (2012) How I treat childhood CML. Blood 119(8):1821–1830PubMedCentralPubMedCrossRefGoogle Scholar
  3. 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. 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):72–77Google Scholar
  5. 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–e210PubMedCrossRefGoogle Scholar
  6. 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):76Google Scholar
  7. 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):721–727PubMedCrossRefGoogle Scholar
  8. 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):838–842PubMedGoogle Scholar
  9. 9.
    Cortes J, Kantarjian H (2003) Advanced-phase chronic myeloid leukemia. Semin Hematol 40(1):79–86PubMedCrossRefGoogle Scholar
  10. 10.
    Cwynarski K, Roberts IA, Iacobelli S et al (2003) Stem cell transplantation for chronic myeloid leukemia in children. Blood 102(4):1224–1231PubMedCrossRefGoogle Scholar
  11. 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):33–47PubMedCrossRefGoogle Scholar
  12. 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):2408–2417PubMedCrossRefGoogle Scholar
  13. 13.
    Faderl S, Talpaz M, Estrov Z et al (1999) The biology of chronic myeloid leukemia. N Engl J Med 341(3):164–172PubMedCrossRefGoogle Scholar
  14. 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):107–112PubMedCrossRefGoogle Scholar
  15. 15.
    Goldman JM (2007) How I treat chronic myeloid leukemia in the imatinib era. Blood 110(8):2828–2837PubMedCrossRefGoogle Scholar
  16. 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):1888–1895PubMedCentralPubMedCrossRefGoogle Scholar
  17. 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):513–521PubMedGoogle Scholar
  18. 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):5591–5599PubMedCrossRefGoogle Scholar
  19. 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):2096–2102PubMedCrossRefGoogle Scholar
  20. 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):850–858PubMedCrossRefGoogle Scholar
  21. 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):686–692PubMedCrossRefGoogle Scholar
  22. 22.
    Hijiya N, Millot F, Suttorp M (2015) Chronic myeloid leukemia in children: clinical findings, management, and unanswered questions. Pediatr Clin N Am 62:107–119CrossRefGoogle Scholar
  23. 23.
    Hochhaus A (2008) Prognostic factors in chronic myeloid leukemia (CML). Onkologie 31(11):576–578PubMedCrossRefGoogle Scholar
  24. 24.
    Hochhaus A (2011) Educational session: managing chronic myeloid leukemia as a chronic disease. Hematol Am Soc Hematol Educ Program 2011:128–135CrossRefGoogle Scholar
  25. 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):1054–1061PubMedCrossRefGoogle Scholar
  26. 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):2016–2022CrossRefGoogle Scholar
  27. 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):3758–3765PubMedCentralPubMedCrossRefGoogle Scholar
  28. 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):1421–1423PubMedCrossRefGoogle Scholar
  29. 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):4524–4526PubMedCentralPubMedCrossRefGoogle Scholar
  30. 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):71–80PubMedCentralPubMedCrossRefGoogle Scholar
  31. 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):2430–2433PubMedCrossRefGoogle Scholar
  32. 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):126–134PubMedCrossRefGoogle Scholar
  33. 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):3944–3945PubMedCrossRefGoogle Scholar
  34. 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):232–238PubMedCrossRefGoogle Scholar
  35. 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):2004–2473Google Scholar
  36. 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):2827–2832PubMedCrossRefGoogle Scholar
  37. 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 #521Google Scholar
  38. 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):231–238PubMedCrossRefGoogle Scholar
  39. 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. 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):2739–2742PubMedCrossRefGoogle Scholar
  41. 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):78–87PubMedCentralPubMedGoogle Scholar
  42. 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):760–765PubMedCrossRefGoogle Scholar
  43. 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):25–32CrossRefGoogle Scholar
  44. 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):1029–1035PubMedCentralPubMedCrossRefGoogle Scholar
  45. 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 #4549Google Scholar
  46. 46.
    Saglio G, Fava C (2012) Practical monitoring of chronic myelogenous leukemia: when to change treatment. J Natl Compr Cancer Netw 10(1):121–129Google Scholar
  47. 47.
    Sokal JE, Cox EB, Baccarani M et al (1984) Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood 63(4):789–799PubMedGoogle Scholar
  48. 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):1352–1357PubMedGoogle Scholar
  49. 49.
    Sokal JE, Baccarani M, Russo D et al (1988) Staging and prognosis in chronic myelogenous leukemia. Semin Hematol 25(1):49–61PubMedGoogle Scholar
  50. 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, 2012Google Scholar
  51. 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. 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 2010:368–376CrossRefGoogle Scholar
  53. 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):351–357PubMedCrossRefGoogle Scholar
  54. 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–S122PubMedCrossRefGoogle Scholar
  55. 55.
    Suttorp M, Eckardt T, Tauer JT et al (2012) Management of chronic myeloid leukemia in childhood. Curr Hematol Malig Rep 7(2):116–124PubMedCrossRefGoogle Scholar
  56. 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):2725Google Scholar
  57. 57.
    Tanaka MF, Kantarjian H, Cortes J et al (2012) Treatment options for chronic myeloid leukemia. Expert Opin Pharmacother 13(6):815–828PubMedCrossRefGoogle Scholar
  58. 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):535–544PubMedCrossRefGoogle Scholar
  59. 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):109–112PubMedCrossRefGoogle Scholar
  60. 60.
    Williams K, Thomson D, Seto I et al (2012) Standard 6: age groups for pediatric trials. Pediatrics 129(Suppl 3):S153–S160PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • David Gurrea Salas
    • 1
  • Ingmar Glauche
    • 2
  • Josephine T. Tauer
    • 1
  • Christian Thiede
    • 3
  • Meinolf Suttorp
    • 1
  1. 1.Pediatric Hematology and Oncology, Department of Pediatrics, University Hospital “Carl Gustav Carus”Technical University DresdenDresdenGermany
  2. 2.Institute for Medical Informatics and BiometryTechnical University DresdenDresdenGermany
  3. 3.Medical Clinic I, Department of Internal Medicine, University Hospital “Carl Gustav Carus”Technical University DresdenDresdenGermany

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