Advertisement

Low Dose Cytosine Arabinoside and Azacitidine Combination in Elderly Patients with Acute Myeloid Leukemia and Refractory Anemia with Excess Blasts (MDS-RAEB2)

  • Figen AtalayEmail author
  • Elif Birtaş Ateşoğlu
Original Article

Abstract

Only one-third of elderly (>60 years) AML and MDS-RAEB2 patients may receive intensive chemotherapy treatment alternatives that are limited in this patient group due to the potential of severe toxicity. Previous studies have shown that azacitidine and low dose cytarabine treatments may be a beneficial treatment option for these patients. In this study, we aimed to good results with low toxicity in elderly patients. We retrospectively analyzed the AML and MDS-RAEB2 patients who received azacitidine monotherapy and azacitidine and LDL-ara-c combination therapy for a comparison of their response to therapy, survival rates, and toxicity rates and for determining the factors that could affect their overall survival. A total of 27 patients who were diagnosed with de novo AML and MDS-RAEB2 and who received at least four cycles of chemotherapy were included in the study, and the data were evaluated retrospectively. When monotherapy and combination therapy groups were compared, the pretreatment bone marrow blast count was observed to be greater in the combination therapy group. A statistically significant difference was not detected between the groups regarding the response to therapy ratios (p = 0.161) (42.9 and 57.1 %, respectively). No difference was detected between the groups regarding therapy-related toxicity. Infections were the most common complication. Progression-free survival was 30.3 % for the azacitidine monotherapy group and 66.7 % for the combination (azacitidine + LD-ara-c) group. The factors influencing the overall survival rate were determined based on the response to the first-line therapies, more than a grade 2 infection, fever, and relapse in a multi-variance analysis. The combination therapy may be a well-tolerated treatment option for the elderly, vulnerable AML patients whose blast count is high in response to therapy rates, overall survival rates, and toxicities are not different, although the pre-treatment bone marrow blast count was greater in the combination therapy groups compared with the monotherapy group.

Keywords

Acute myeloid leukemia Elderly Azacitidine Low dose cytarabine 

Notes

Acknowledgments

This study was approved by the Başkent University Medical and Health Sciences Research Committee and Ethics Committee (Project Number: KA14/105) and supported by the Başkent University Research Fund.

References

  1. 1.
    Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK et al (2007) A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer 109:1114–1124CrossRefPubMedGoogle Scholar
  2. 2.
    Al-Ali HK, Jaekel N, Junghanss C, Maschmeyer G, Krahl R, Cross M et al (2012) Azacytidine in patients with acute myeloid leukemia medically unfit for or resistant to chemotherapy: a multicenter phase I/II study. Leuk Lymphoma 53:110–117CrossRefPubMedGoogle Scholar
  3. 3.
    Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z (2008) A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood 112:1638–1645PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Tavor S, Rahamim E, Sarid N, Rozovski U, Gibstein L, Aviv F et al (2012) High response rate for treatment with gemtuzumab ozogamicin and cytarabine in elderly patients with acute myeloid leukemia and favorable and intermediate-I cytogenetic risk. Clin Lymphoma Myeloma Leuk 12:438–443CrossRefPubMedGoogle Scholar
  5. 5.
    Borthakur G, Huang X, Kantarjian H, Faderl S, Ravandi F, Ferrajoli A et al (2010) Report of a phase 1/2 study of a combination of azacytidine and cytarabine in acute myelogenous leukemia and high-risk myelodysplastic syndromes. Leuk Lymphoma 51:73–78PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Silverman LR, McKenzie DR, Peterson BL, Holland JF, Backstrom JT, Beach CL et al (2006) Further analysis of trials with azacytidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 24:3895–3903CrossRefPubMedGoogle Scholar
  7. 7.
    Itzykson R, Thépot S, Quesnel B, Dreyfus F, Beyne-Rauzy O, Turlure P et al (2011) Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacytidine. Blood 117:403–411CrossRefPubMedGoogle Scholar
  8. 8.
    Moon JH, Lee SJ, Lee YJ, Kang BW, Chae YS, Kim JG et al (2012) Pilot study on combination of azacytidine and low-dose cytarabine for patients with refractory anemia with excess blast. Ann Hematol 91:367–373CrossRefPubMedGoogle Scholar
  9. 9.
    Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951CrossRefPubMedGoogle Scholar
  10. 10.
    Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH et al (2003) 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 21:4642–4649CrossRefPubMedGoogle Scholar
  11. 11.
    Radujkovic A, Dietrich S, Bochtler T, Krämer A, Schöning T, Ho AD et al (2014) Azacytidine and low-dose cytarabine in palliative patients with acute myeloid leukemia and high bone marrow blast counts–a retrospective single-center experience. Eur J Haematol 93:112–117CrossRefPubMedGoogle Scholar
  12. 12.
    Pleyer L, Stauder R, Burgstaller S, Schreder M, Tinchon C, Pfeilstocker M et al (2013) Azacytidine in patients with WHO-defined AML—results of 155 patients from the Austrian Azacytidine Registry of the AGMT-Study Group. J Hematol Oncol 6:32PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Thépot S, Itzykson R, Seegers V, Recher C, Raffoux E, Quesnel B et al (2014) Azacytidine in untreated acute myeloid leukemia: a report on 149 patients. Am J Hematol 89:410–416CrossRefPubMedGoogle Scholar
  14. 14.
    Pleyer L, Burgstaller S, Girschikofsky M, Linkesch W, Stauder R, Pfeilstocker M et al (2014) Azacytidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacytidine Registry of the AGMT-Study Group. Ann Hematol 93:1825–1838PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Pollyea DA, Zehnder J, Coutre S, Gotlib JR, Gallegos L, Abdel-Wahab O et al (2013) Sequential azacytidine plus lenalidomide combination for elderly patients with untreated acute myeloid leukemia. Haematologica 98:591–596PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Govindaraj C, Tan P, Walker P, Wei A, Spencer A, Plebanski M (2014) Reducing TNF receptor 2 + regulatory T cells via the combined action of azacytidine and the HDAC inhibitor, panobinostat for clinical benefit in acute myeloid leukemia patients. Clin Cancer Res 20:724–735CrossRefPubMedGoogle Scholar
  17. 17.
    Walker AR, Klisovic RB, Garzon R, Schaaf LJ, Humphries K, Devine SM (2014) Phase I study of azacytidine and bortezomib in adults with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma 55:1304–1308PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Lainey E, Wolfromm A, Marie N, Enot D, Scoazec M, Bouteloup C et al (2013) Azacytidine and erlotinib exert synergistic effects against acute myeloid leukemia. Oncogene 32:4331–4342CrossRefPubMedGoogle Scholar
  19. 19.
    Foran JM (2010) New prognostic markers in acute myeloid leukemia: perspective from the clinic. Hematol Am Soc Hematol Educ Program 2010:47–55CrossRefGoogle Scholar
  20. 20.
    Chen CC, Yang CF, Yang MH, Lee KD, Kwang WK, You J et al (2005) Pretreatment prognostic factors and treatment outcome in elderly patients with de novo acute myeloid leukemia. Ann Oncol 16:1366–1373CrossRefPubMedGoogle Scholar
  21. 21.
    Maurillo L, Venditti A, Spagnoli A, Gaidano G, Ferrero D, Oliva E (2012) Azacytidine for the treatment of patients with acute myeloid leukemia: report of 82 patients enrolled in an Italian Compassionate Program. Cancer 118:1014–1022CrossRefPubMedGoogle Scholar
  22. 22.
    Sudan N, Rossetti JM, Shadduck RK, Latsko J, Lech JA, Kaplan RB et al (2006) Treatment of acute myelogenous leukemia with outpatient azacytidine. Cancer 107:1839–1843CrossRefPubMedGoogle Scholar

Copyright information

© Indian Society of Haematology & Transfusion Medicine 2015

Authors and Affiliations

  1. 1.Department of HematologyBaskent University School of MedicineİstanbulTurkey
  2. 2.Department of HematologyKocaeli University School of MedicineKocaeliTurkey

Personalised recommendations