Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Therapy

Homoharringtonine in combination with cytarabine and aclarubicin resulted in high complete remission rate after the first induction therapy in patients with de novo acute myeloid leukemia

Abstract

To assess the efficacy and toxicity of HAA regimen (homoharritonine 4 mg/m2/day, days 1–3; cytarabine 150 mg/m2/day, days 1–7; aclarubicin 12 mg/m2/day, days 1–7) as an induction therapy in the treatment of de novo acute myeloid leukemia (AML), 48 patients with newly diagnosed AML, aged 35 (14–57) years, were entered into this clinical study. The median follow-up was 26 months. Eighty-three percent of patients achieved complete remission (CR), and the first single course of induction HAA regimen resulted in CR rate of 79%. The CR rate of 100, 82 and 33% were achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. For all patients who achieved CR, the median time from the initiation of the induction therapy to the evaluation of the remission status was 32 days. For all patients, the estimated 3 years overall survival (OS) rate was 53%, whereas for patients with M5, the estimated OS rate at 3 years was 75%. The toxicities associated with HAA regimen were acceptable, and the most common toxicity was infection. This study suggested that HAA regimen might be a well-tolerable, effective induction regimen in young adult patients with AML.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Yates J, Glidewell O, Wiernik P, Cooper MR, Steinberg D, Dosik H et al. Cytosine arabinoside with daunorybicin or adriamycin therapy with acute myelocytic leukemia: a CALGB study. Blood 1982; 60: 454–463.

    CAS  PubMed  Google Scholar 

  2. Berman E, Helle GR, Santorsa J, McKenzie S, Gee T, Kempin S et al. Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Blood 1991; 77: 1666–1674.

    CAS  PubMed  Google Scholar 

  3. Wiernik PH, Banks PL, Case Jr DC, Arlin ZA, Periman PO, Todd MB et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood 1992; 79: 313–319.

    CAS  PubMed  Google Scholar 

  4. Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA et al. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study. J Clin Oncol 1992; 10: 1103–1111.

    Article  CAS  Google Scholar 

  5. Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP et al. A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubincin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood 1996; 88: 2841–2851.

    CAS  PubMed  Google Scholar 

  6. Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D et al. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood 1996; 87: 1710–1717.

    CAS  PubMed  Google Scholar 

  7. Schiller G, Gajewski J, Nimer S, Territo M, Ho W, Lee M et al. A randomized study of intermediate versus conventional-dose cytarabine as intensive induction for acute myelogenous leukemia. Br J Haematol 1992; 81: 170–177.

    Article  CAS  Google Scholar 

  8. Bishop JF, Lowenthal RM, Joshua D, Matthews JP, Todd D, Cobcroft R et al. Etoposide in acute non-lymphocytic leukemia. Blood 1990; 75: 27–32.

    CAS  PubMed  Google Scholar 

  9. Ian MH, Richard FS, Anthony HG, John KHR, Keith W, Richard GG et al. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the Medical Research Council's 10th AML trial (MRC AML 10). Blood 1997; 89: 2308–2311.

    Google Scholar 

  10. Hwang WL, Young JH, Gau JP, Hu HT, Tsai YT . DAE (daunorubicin, Ara-C, and etoposide) and intermediate dose Ara-C for remission induction and consolidation treatment of adult patients with acute myeloid leukemia. Am J Clin Oncol 1992; 15: 531–534.

    Article  CAS  Google Scholar 

  11. Bradstock KF, Matthews JP, Lowenthal RM, Baxter H, Catalano J, Brighton T et al. The Australasian Leukaemia Lymphoma Group. A randomized trial of high- versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine. Blood 2005; 105: 481–488.

    Article  CAS  Google Scholar 

  12. Baaske DM, Heinstein P . Cytotoxicity and cell cycle specificity of homoharringtonine. Antimicrob Agents Chemother 1977; 12: 298–300.

    Article  CAS  Google Scholar 

  13. Takemura Y, Ohnuma T, Chou TC, Okano T, Holland JF . Biologic and pharmacologic effects of harringtonine on human leukemia-lymphoma cells. Cancer Chemother Pharmacol 1985; 14: 206–210.

    Article  CAS  Google Scholar 

  14. Zhou JY, Chen DL, Shen ZS, Koeffler HP . Effect of homoharringtonine on proliferation and differentiation of human leukemic cells in vitro. Cancer Res 1990; 50: 2031–2035.

    CAS  PubMed  Google Scholar 

  15. Wilkoff LJ, Dulmadge DA, Laster Jr WR, Griswold Jr DP . Effect of homoharringtonine on the viability of murine leukemia P388 cells resistant to either adriamycin, vincristine, or 1-beta-D-arabinofuranosylcytosine. Cancer Chemother Pharmacol 1989; 23: 145–150.

    Article  CAS  Google Scholar 

  16. Fanucchi MP, Kong XR, Chou TC . Hexamethylene bisacetamide (HMBA) does not enhance the cytotoxic effects of adriamycin (ADR), 1,beta-D-arabinofuranosylcytosine (ARA-C) and harringtonine (HT) in HL-60 cells [abstract 1492]. Proc Am Assoc Cancer Res 1986; 27: 376.

    Google Scholar 

  17. Bian SG, Hao YS, Wang ZC . Analysis of the therapeutic efficacy and prognostic factors of intensive chemotherapy in 91 patients with acute nonlymphoblastic leukemia. Chung Hua Nei Ko Tsa Chih 1990; 29: 225–260.

    Google Scholar 

  18. Takahashi I, Hara M, Uchida K, Takaoka K, Watanabe S, Lai M et al. Treatment of relapsed acute myelocytic leukemia with a combination of aclarubicin and cytosine arabinoside. Acta Med Okayama 1982; 36: 77–80.

    CAS  PubMed  Google Scholar 

  19. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposed revised criteria for the classification of acute myeloid leukemia. Ann Intern Med 1985; 103: 620–625.

    Article  CAS  Google Scholar 

  20. World Health Organization. A Handbook for Reporting Results of Cancer Treatment. WHO Publications: Geneva, 1979.

  21. Kaplan EL, Meier P . Nonparametric estimation of incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  22. Tong Y, Huang J, Jin J, Ye X-J, Mong H-T, Mai W-Y et al. Clinical analysis of induction chemotherapy in adult patients with acute myeloid leukemia (in Chinese). Shi Yong Zhong Liu Za Zhi 2002; 17: 191–193.

    Google Scholar 

  23. Richard MS, Margaret RO, Mikkael A . Sekeres: acute myeloid leukemia. Hematology 2004, 98–117.

  24. Bennett JM, Young ML, Andersen JW, Cassileth PA, Tallman MS, Paietta E et al. Long-term survival in acute myeloid leukemia: the Eastern Cooperative Oncology Group experience. Cancer 1997; 80: 2205–2209.

    Article  CAS  Google Scholar 

  25. Tallman MS, Gary Gilliland D, Rowe JM . Drug therapy for acute myeloid leukemia. Blood 2005; 106: 1154–1163.

    Article  CAS  Google Scholar 

  26. Kern W, Haferlach T, Schoch C, Loffler H, Gassmann W, Heinecke A et al. Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 trial. Blood 2003; 101: 64–70.

    Article  CAS  Google Scholar 

  27. Buchner T, Urbanitz D, Hiddemann W, Ruhl H, Ludwig WD, Fischer J et al. Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multicenter studies of the German AML Cooperative Group. J Clin Oncol 1985; 3: 1583–1589.

    Article  CAS  Google Scholar 

  28. Wheatley K, Burnett AK, Goldstone AH, Gray RG, Hann IM, Harrison CJ et al. A simple, robust, validated and highly predictive index for acute myeloid leukemia 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  Google Scholar 

  29. He XY, Pohlman B, Lichtin A, Rybicki L, Kalaycio M . Timed-sequential chemotherapy with concomitant granulocyte colony-stimulating factor for newly diagnosed de novo acute myelogenous leukemia. Leukemia 2003; 17: 1078–1084.

    Article  CAS  Google Scholar 

  30. Legha SS, Keating M, Picket S, Ajani JA, Ewer M, Bodey GP . Phase I clinical investigation of homoharringtonine. Cancer Treat Rep 1984; 68: 1085–1091.

    CAS  PubMed  Google Scholar 

  31. Warrell Jr RP, Coonley CJ, Gee TS . Homoharringtonine: an effective new drug for remission induction in refractory nonlymphoblastic leukemia. J Clin Oncol 1985; 3: 617–621.

    Article  Google Scholar 

  32. Iwata N, Karasawa M, Omine M, Maekawa T, Suzuki T, Kawai Y . Aclarubicin-associated QTc prolongation and ventricular fibrillation. Cancer Treat Rep 1984; 68: 527–529.

    CAS  PubMed  Google Scholar 

  33. Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A et al. Polish Adult Leukemia Group (PALG). Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study. Leukemia 2004; 18: 989–997.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Gang Ye for critically reviewing the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J Jin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jin, J., Jiang, DZ., Mai, WY. et al. Homoharringtonine in combination with cytarabine and aclarubicin resulted in high complete remission rate after the first induction therapy in patients with de novo acute myeloid leukemia. Leukemia 20, 1361–1367 (2006). https://doi.org/10.1038/sj.leu.2404287

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404287

Keywords

This article is cited by

Search

Quick links