Skip to main content
SpringerLink
Log in

Prior hypomethylating agent use lacks impact on clinical outcome in patients with secondary acute myeloid leukemia arising from myelodysplastic syndromes treated with standard induction chemotherapy

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

Abstract

Patients with secondary acute myeloid leukemia (sAML) arising from prior myelodysplastic syndromes have poor prognosis. Anthracycline plus cytarabine (7 + 3) is a standard treatment option for patients who are fit for intensive therapy. In the present study, 22 of 96 sAML patients (23 %) were treated with 7 + 3 and achieved median overall survival (OS) of 9.8 months. Hypomethylating agents (HMA) were given for MDS in 6/22 (28 %) of the patients. When evaluating the prior HMA group, CR/CRi was 50 % for those with prior HMA exposure and 63 % for those without HMA exposure (P = 0.6). Median OS was 14 months for prior HMA exposure vs 10 months for no prior HMA (P = 0.9). The outcome of sAML patients who were treated with 7 + 3 continues to be poor. No statistical significant difference was found between response rates and mOS between prior HMA exposure or not. Additional larger studies are needed to confirm our results.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937–51.

    Article  CAS  PubMed  Google Scholar 

  2. Prebet T, Gore SD, Thepot S, et al. Outcome of acute myeloid leukaemia following myelodysplastic syndrome after azacitidine treatment failure. Br J Haematol. 2012;157:764–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wahlin A, Markevarn B, Golovleva I, Nilsson M. Prognostic significance of risk group stratification in elderly patients with acute myeloid leukaemia. Br J Haematol. 2001;115:25–33.

    Article  CAS  PubMed  Google Scholar 

  4. Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood. 2006;107:3481–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Farag SS, Archer KJ, Mrozek K, et al. Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461. Blood. 2006;108:63–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Juliusson G, Antunovic P, Derolf A, et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 2009;113:4179–87.

    Article  CAS  PubMed  Google Scholar 

  7. Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. New Eng J Med. 2009;361:1249–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nimer SD. Myelodysplastic syndromes. Blood. 2008;111:4841–51.

    Article  CAS  PubMed  Google Scholar 

  9. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Silverman LR, McKenzie DR, Peterson BL, et al. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24:3895–903.

    Article  CAS  Google Scholar 

  11. Bello C, Yu D, Komrokji RS, et al. Outcomes after induction chemotherapy in patients with acute myeloid leukemia arising from myelodysplastic syndrome. Cancer. 2011;117:1463–9.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 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 Off J Am Soc Clin Oncol. 2003;21:4642–9.

    Article  Google Scholar 

  13. Buchner T, Schlenk RF, Schaich M, et al. Acute myeloid leukemia (AML): different treatment strategies versus a common standard arm—combined prospective analysis by the German AML intergroup. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30:3604–10.

    Article  Google Scholar 

  14. Liu J, Mi Y, Fu M, et al. Intensive induction chemotherapy with regimen containing intermediate dose cytarabine in the treatment of de novo acute myeloid leukemia. Am J Hematol. 2009;84:422–7.

    Article  CAS  PubMed  Google Scholar 

  15. Bertoli S, Berard E, Huguet F, et al. Time from diagnosis to intensive chemotherapy initiation does not adversely impact the outcome of patients with acute myeloid leukemia. Blood. 2013;121:2618–26.

    Article  CAS  PubMed  Google Scholar 

  16. Pagnano KB, Traina F, Takahashi T, et al. Conventional chemotherapy for acute myeloid leukemia: a Brazilian experience. Sao Paulo Med J (Rev Paul Med). 2000;118:173–8.

    CAS  Google Scholar 

  17. Bishop JF, Matthews JP, Young GA, et al. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996;87:1710–7.

    CAS  PubMed  Google Scholar 

  18. Yoon JH, Cho BS, Kim HJ, et al. Outcomes of elderly de novo acute myeloid leukemia treated by a risk-adapted approach based on age, comorbidity, and performance status. Am J Hematol. 2013;88:1074–81.

    Article  CAS  PubMed  Google Scholar 

  19. Heil G, Mitrou PS, Hoelzer D, et al. High-dose cytosine arabinoside and daunorubicin postremission therapy in adults with de novo acute myeloid leukemia. Long-term follow-up of a prospective multicenter trial. Ann Hematol. 1995;71:219–25.

    Article  CAS  PubMed  Google Scholar 

  20. Schiffer CA. “I am older, not elderly,” said the patient with acute myeloid leukemia. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28:521–3.

    Article  Google Scholar 

  21. Sekeres MA, Peterson B, Dodge RK, et al. Differences in prognostic factors and outcomes in African Americans and whites with acute myeloid leukemia. Blood. 2004;103:4036–42.

    Article  CAS  PubMed  Google Scholar 

  22. Olesen LH, Aggerholm A, Andersen BL, et al. Molecular typing of adult acute myeloid leukaemia: significance of translocations, tandem duplications, methylation, and selective gene expression profiling. Br J Haematol. 2005;131:457–67.

    Article  CAS  PubMed  Google Scholar 

  23. Mrozek K, Heerema NA, Bloomfield CD. Cytogenetics in acute leukemia. Blood Rev. 2004;18:115–36.

    Article  PubMed  Google Scholar 

  24. Grimwade D. The clinical significance of cytogenetic abnormalities in acute myeloid leukaemia. Best Pract Res Clin Haematol. 2001;14:497–529.

    Article  CAS  PubMed  Google Scholar 

  25. Feldman EJ. Does therapy-related AML have a poor prognosis, independent of the cytogenetic/molecular determinants? Best Pract Res Clin Haematol. 2011;24:523–6.

    Article  PubMed  Google Scholar 

  26. Schoch C, Kern W, Schnittger S, et al. Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML. Leukemia. 2004;18:120–5.

    Article  CAS  PubMed  Google Scholar 

  27. Kayser S, Dohner K, Krauter J, et al. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood. 2011;117:2137–45.

    Article  CAS  PubMed  Google Scholar 

  28. Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116:354–65.

    Article  CAS  PubMed  Google Scholar 

  29. Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1312–20.

    Article  CAS  PubMed  Google Scholar 

  30. Jabbour E, Ghanem H, Huang X, et al. Acute myeloid leukemia after myelodysplastic syndrome and failure of therapy with hypomethylating agents: an emerging entity with a poor prognosis. Clin Lymphoma Myeloma Leuk. 2014;14:93–7.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Salih Subari, Firas Baidoun, Muhanad Hreh, Mrinal Patnaik, Shahrukh Hashmi, Michelle Elliott, William Hogan, Mark Litzow & Aref Al-Kali

Authors
  1. Salih Subari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Firas Baidoun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Muhanad Hreh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mrinal Patnaik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shahrukh Hashmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michelle Elliott
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. William Hogan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mark Litzow
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Aref Al-Kali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aref Al-Kali.

Ethics declarations

Conflict of interest

Authors declare no conflict of interest.

Funding

None.

Additional information

Part of this manuscript was accepted at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting, Chicago, USA.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Subari, S., Baidoun, F., Hreh, M. et al. Prior hypomethylating agent use lacks impact on clinical outcome in patients with secondary acute myeloid leukemia arising from myelodysplastic syndromes treated with standard induction chemotherapy. Int J Hematol 103, 409–415 (2016). https://doi.org/10.1007/s12185-016-1935-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-016-1935-0

Keywords

Search

Navigation