Skip to main content
SpringerLink
Log in

Prognostic Factors in Pediatric Acute Myeloid Leukemia

  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Acute myeloid leukemia (AML), a heterogeneous group of diseases with variable responses to the same therapy, comprises nearly a quarter of childhood acute leukemias. Although historically very few prognostic markers have been incorporated into therapeutic decision making in AML, recent advances in technology have enabled identification of numerous factors associated with disease outcome. This review provides a detailed analysis of most clinically relevant factors associated with disease outcome in childhood AML.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular ineterest, published recently, have been highlighted as:• Of importance

  1. De Angulo G, Yuen C, Palla SL, et al.: Absolute lymphocyte count is a novel prognostic indicator in ALL and AML: implications for risk stratification and future studies. Cancer 2008, 112:407–415.

    Article  PubMed  Google Scholar 

  2. De Botton S, Coiteux V, Chevret S, et al.: Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy. J Clin Oncol 2004, 22:1404–1412.

    Article  PubMed  Google Scholar 

  3. Gamis AS, Woods WG, Alonzo TA, et al.: Increased age at diagnosis has a significantly negative effect on outcome in children with Down syndrome and acute myeloid leukemia: a report from the Children’s Cancer Group Study 2891. J Clin Oncol 2003, 21:3415–3422.

    Article  PubMed  Google Scholar 

  4. Kaspers GJ, Zwaan CM: Pediatric acute myeloid leukemia: towards high-quality cure of all patients. Haematologica 2007, 92(11):1519–1532.

    Article  PubMed  Google Scholar 

  5. Meshinchi S, Arceci RJ: Prognostic factors and risk-based therapy in pediatric acute myeloid leukemia. Oncologist 2007, 12:341–355.

    Article  PubMed  Google Scholar 

  6. Creutzig U, Ritter J, Riehm H, et al.: Improved treatment results in childhood acute myelogenous leukemia: a report of the German Cooperative Study AML-BFM-78. Blood 1985, 65:298–304.

    CAS  PubMed  Google Scholar 

  7. Lange BJ, Smith FO, Feusner J, et al.: Outcomes in CCG-2961, a Children’s Oncology Group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the Children’s Oncology Group. Blood 2008, 111:1044–1053.

    Article  CAS  PubMed  Google Scholar 

  8. Aplenc R, Alonzo TA, Gerbing RB, et al.: Ethnicity and survival in childhood acute myeloid leukemia: a report from the Children’s Oncology Group. Blood 2006, 108:74–80.

    Article  CAS  PubMed  Google Scholar 

  9. Rubnitz JE, Lensing S, Razzouk BI, et al.: Effect of race on outcome of white and black children with acute myeloid leukemia: the St. Jude experience. Pediatr Blood Cancer 2007, 48:10–15.

    Article  Google Scholar 

  10. Davies SM, Robison LL, Buckley JD, et al.: Glutathione S-transferase polymorphisms and outcome of chemotherapy in childhood acute myeloid leukemia. J Clin Oncol 2001, 19(5):1279–1287.

    PubMed  Google Scholar 

  11. Damm F, Heuser M, Morgan M, et al.: Single nucleotide polymorphism in the mutational hotspot of WT1 predicts a favorable outcome in patients with cytogenetically normal acute myeloid leukemia. J Clin Oncol 2010, 28:578–585.

    Article  CAS  PubMed  Google Scholar 

  12. Lange BJ, Gerbing RB, Feusner J, et al.: Mortality in overweight and underweight children with acute myeloid leukemia. JAMA 2005, 293:203–211.

    Article  CAS  PubMed  Google Scholar 

  13. Chessells JM, Harrison CJ, Kempski H, et al.: Clinical features, cytogenetics and outcome in acute lymphoblastic and myeloid leukaemia of infancy: report from the MRC Childhood Leukaemia Working Party. Leukemia 2002, 16:776–784.

    Article  CAS  PubMed  Google Scholar 

  14. Cheson BD, Bennett JM, Kopecky KJ, et al.: Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003, 21:4642–4649.

    Article  PubMed  Google Scholar 

  15. Sievers EL, Lange BJ, Alonzo TA, et al.: Immunophenotypic evidence of leukemia after induction therapy predicts relapse: results from a prospective Children’s Cancer Group study of 252 patients with acute myeloid leukemia. Blood 2003, 101:3398–3406.

    Article  CAS  PubMed  Google Scholar 

  16. Grimwade D, Hills RK: Independent prognostic factors for AML outcome. Hematology Am Soc Hematol Educ Program 2009, 385–395.

  17. Wheatley K, Burnett AK, Goldstone AH, et al.: A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial. United Kingdom Medical Research Council’s Adult and Childhood Leukaemia Working Parties. Br J Haematol 1999, 107:69–79.

    Article  CAS  PubMed  Google Scholar 

  18. Elliott MA, Litzow MR, Letendre LL, et al.: Early peripheral blood blast clearance during induction chemotherapy for acute myeloid leukemia predicts superior relapse-free survival. Blood 2007, 110:4172–4174.

    Article  CAS  PubMed  Google Scholar 

  19. Wells RJ, Arthur DC, Srivastava A, et al.: Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children’s Cancer Group Study 213. Leukemia 2002, 16:601–607.

    Article  CAS  PubMed  Google Scholar 

  20. Coustan-Smith E, Ribeiro RC, Rubnitz JE, et al.: Clinical significance of residual disease during treatment in childhood acute myeloid leukaemia. Br J Haematol 2003, 123:243–252.

    Article  PubMed  Google Scholar 

  21. Langebrake C, Creutzig U, Dworzak M, et al.: Residual disease monitoring in childhood acute myeloid leukemia by multiparameter flow cytometry: the MRD-AML-BFM Study Group. J Clin Oncol 2006, 24:3686–3692.

    Article  PubMed  Google Scholar 

  22. • Meshinchi S, Alonzo T, Gerbing RB, et al.: Minimal residual disease detection by four-color multidimensional flow cytometry identifies pediatric AML patients at high risk of relapse [abstract]. Blood (ASH Annual Meeting Abstracts) 2007, 110:Abstract 1429. Four-color flow MRD is now being considered as an important method that will significantly change our future risk stratification and how we manage AML.

  23. Maurillo L, Buccisano F, Del Principe MI, et al.: Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia. J Clin Oncol 2008, 26:4944–4951.

    Article  PubMed  Google Scholar 

  24. Avivi I, Rowe JM: Prognostic factors in acute myeloid leukemia. Curr Opin Hematol 2005, 12:62–67.

    Article  CAS  PubMed  Google Scholar 

  25. Grimwade D, Walker H, Oliver F, et al.: The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood 1998, 92:2322–2333.

    CAS  PubMed  Google Scholar 

  26. Hann IM, Webb DK, Gibson BE, et al.: MRC trials in childhood acute myeloid leukaemia. Ann Hematol 2004, 83(Suppl 1):S108–S112.

    PubMed  Google Scholar 

  27. Hasle H, Alonzo TA, Auvrignon A, et al.: Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. Blood 2007, 109:4641–4647.

    Article  CAS  PubMed  Google Scholar 

  28. Löwenberg B, Downing JR, Burnett A: Acute myeloid leukemia. N Engl J Med 1999, 341:1051–1062.

    Article  PubMed  Google Scholar 

  29. Breems DA, Van Putten WL, De Greef GE, et al.: Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol 2008, 26:4791–4797.

    Article  PubMed  Google Scholar 

  30. Raimondi SC, Chang MN, Ravindranath Y, et al.: Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a Cooperative Pediatric Oncology Group Study—POG 8821. Blood 1999, 94(11):3707–3716.

    CAS  PubMed  Google Scholar 

  31. • Balgobind BV, Raimondi SC, Harbott J, et al.: Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 2009, 114(12):2489–2496. This paper emphasizes our evolving knowledge of cytogenetics and molecular genetics and how these risk factors are better delineated through large cooperative studies.

    Article  CAS  PubMed  Google Scholar 

  32. Bacher U, Haferlach C, Kern W, et al.: Prognostic relevance of FLT3-TKD mutations in AML: the combination matters—an analysis of 3082 patients. Blood 2008, 111(5):2527–2537.

    Article  CAS  PubMed  Google Scholar 

  33. Mrozek K, Marcucci G, Paschka P, et al.: Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: Are we ready for a prognostically prioritized molecular classification? Blood 2007, 109:431–448.

    Article  CAS  PubMed  Google Scholar 

  34. Meshinchi S, Alonzo TA, Stirewalt DL, et al.: Clinical implications of FLT3 mutations in pediatric AML. Blood 2006, 108:3654–3661.

    Article  CAS  PubMed  Google Scholar 

  35. Stone RM: Prognostic factors in AML in relation to (ab)normal karyotype. Best Pract Res Clin Haematol 2009, 22:523–528.

    Article  CAS  PubMed  Google Scholar 

  36. Hollink IH, Zwaan CM, Zimmermann M, et al.: Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML. Leukemia 2009, 23(2):262–270.

    Article  CAS  PubMed  Google Scholar 

  37. Schiffer CA: Molecular characterization of AML: a significant advance or just another prognostic factor? Best Pract Res Clin Haematol 2008, 21:621–628.

    Article  CAS  PubMed  Google Scholar 

  38. Frohling S, Schlenk RF, Stolze I, et al.: CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations. J Clin Oncol 2004, 22:624–633.

    Article  PubMed  Google Scholar 

  39. Marcucci G, Mrozek K, Ruppert AS, et al.: Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a Cancer and Leukemia Group B study. J Clin Oncol 2005, 23:5705–5717.

    Article  PubMed  Google Scholar 

  40. Ho PA, Alonzo TA, Gerbing RB, et al.: Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children’s Oncology Group. Blood 2009, 113:6558–6566.

    Article  CAS  PubMed  Google Scholar 

  41. Noronha SA, Farrar JE, Alonzo TA, et al.: WT1 expression at diagnosis does not predict survival in pediatric AML. Pediatr Blood Cancer 2009, 53:1136–1139.

    Article  PubMed  Google Scholar 

  42. Paschka P, Marcucci G, Ruppert AS, et al.: Wilms’ tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 2008, 26:4595–4602.

    Article  CAS  PubMed  Google Scholar 

  43. Gaidzik VI, Schlenk RF, Moschny S, et al.: Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group. Blood 2009, 113(19):4505–4511.

    Article  CAS  PubMed  Google Scholar 

  44. Pollard JA, Zeng R, Ho P, et al.: Prevalence and prognostic implications of WT1 mutations in pediatric AML: a report from Children’s Oncology Group [abstract]. Blood (ASH Annual Meeting Abstracts) 2008, 112:Abstract 143.

  45. Cairoli R, Beghini A, Grillo G, et al.: Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood 2006, 107:3463–3468.

    Article  CAS  PubMed  Google Scholar 

  46. Shimada A, Taki T, Tabuchi K, et al.: KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group. Blood 2006, 107:1806–1809.

    Article  CAS  PubMed  Google Scholar 

  47. Paschka P, Marcucci G, Ruppert AS, et al.: Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol 2006, 24:3904–3911.

    Article  CAS  PubMed  Google Scholar 

  48. Paschka P, Du J, Schlenk RF, et al.: Type and number of secondary molecular lesions improve outcome prediction in acute myeloid leukemia (AML) with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG) [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:Abstract 824.

  49. • Pollard JA, Alonzo TA, Gerbing RB: Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML. Blood 2010, 115(12):2372–2379. These data emphasize that one needs to validate initial findings (ie, they need to be generalizable to pediatric patients and they need to be reproducible) before incorporating them into stratification and therapeutic decisions.

    Article  CAS  PubMed  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Children’s Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA

    Mohamed Radhi & Alan Gamis

  2. Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D5-380, P.O. Box 19024, Seattle, WA, 98109-1024, USA

    Soheil Meshinchi

Authors
  1. Mohamed Radhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Soheil Meshinchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan Gamis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohamed Radhi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Radhi, M., Meshinchi, S. & Gamis, A. Prognostic Factors in Pediatric Acute Myeloid Leukemia. Curr Hematol Malig Rep 5, 200–206 (2010). https://doi.org/10.1007/s11899-010-0060-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11899-010-0060-z

Keywords

Search

Navigation