Skip to main content
SpringerLink
Log in

Autologous hematopoietic cell transplantation following high-dose cytarabine consolidation for core-binding factor-acute myeloid leukemia in first complete remission: a phase 2 prospective trial

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

Abstract

Core-binding factor (CBF)-acute myeloid leukemia (AML) generally have a favorable prognosis. However, approximately 50% of patients experience disease relapse during or after post-remission therapy. Retrospective studies on autologous hematopoietic cell transplantation (AHCT) have shown improved survival with decreased relapse rate in CBF-AML. In this prospective study, we evaluate the outcomes of AHCT following high-dose cytarabine (HiDAC) consolidation in patients with CBF-AML in first complete remission (CR). Adult patients with CBF-AML achieving first CR after induction chemotherapy were eligible for the study. High-dose chemotherapy before AHCT included intravenous busulfan (3.2 mg/kg/day, days − 7 to − 5) and etoposide (400 mg/m2/day, days − 3 to − 2). Twenty-nine patients, 17 with t(8;21) and 12 with inv(16), underwent AHCT following 2 or 3 courses of HiDAC consolidation. The estimated 5-year overall and disease-free survival rates were between 89.0% and 82.5%, respectively. The cumulative incidences of relapse and non-relapse mortality were between 17.5% and 0%, respectively. Presence of measurable residual disease (MRD) before AHCT and KIT mutation were significantly associated with relapse after transplantation. In conclusion, the post-remission strategy of AHCT following HiDAC consolidation in CBF-AML was feasible and efficacious. Assays for MRD and KIT mutation may guide selection of patients who will benefit from AHCT in CBF-AML in first CR.

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. Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47. https://doi.org/10.1182/blood-2016-08-733196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Marcucci G, Mrozek K, Ruppert AS, Maharry K, Kolitz JE, Moore JO, 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;23:5705–17. https://doi.org/10.1200/JCO.2005.15.610.

    Article  PubMed  Google Scholar 

  3. Schlenk RF, Benner A, Krauter J, Buchner T, Sauerland C, Ehninger G, et al. Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia: a survey of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol. 2004;22:3741–50. https://doi.org/10.1200/JCO.2004.03.012.

    Article  CAS  PubMed  Google Scholar 

  4. Prebet T, Boissel N, Reutenauer S, Thomas X, Delaunay J, Cahn JY, et al. Acute myeloid leukemia with translocation (8;21) or inversion (16) in elderly patients treated with conventional chemotherapy: a collaborative study of the French CBF-AML intergroup. J Clin Oncol. 2009;27:4747–53. https://doi.org/10.1200/JCO.2008.21.0674.

    Article  PubMed  Google Scholar 

  5. Bloomfield CD, Lawrence D, Byrd JC, Carroll A, Pettenati MJ, Tantravahi R, et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res. 1998;58:4173–9.

    CAS  PubMed  Google Scholar 

  6. Miyawaki S, Ohtake S, Fujisawa S, Kiyoi H, Shinagawa K, Usui N, et al. A randomized comparison of 4 courses of standard-dose multiagent chemotherapy versus 3 courses of high-dose cytarabine alone in postremission therapy for acute myeloid leukemia in adults: the JALSG AML201 Study. Blood. 2011;117:2366–72. https://doi.org/10.1182/blood-2010-07-295279.

    Article  CAS  PubMed  Google Scholar 

  7. Paschka P, Döhner K. Core-binding factor acute myeloid leukemia: can we improve on HiDAC consolidation? Hematol Am Soc Hematol Educ Program. 2013;2013:209–19. https://doi.org/10.1182/asheducation-2013.1.209.

    Article  Google Scholar 

  8. Yoon JH, Kim HJ, Kim JW, Jeon YW, Shin SH, Lee SE, et al. Identification of molecular and cytogenetic risk factors for unfavorable core-binding factor-positive adult AML with post-remission treatment outcome analysis including transplantation. Bone Marrow Transplant. 2014;49:1466–74. https://doi.org/10.1038/bmt.2014.180.

    Article  CAS  PubMed  Google Scholar 

  9. Cornelissen JJ, Versluis J, Passweg JR, van Putten WL, Manz MG, Maertens J, et al. Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40–60 years. Leukemia. 2015;29:1041–50. https://doi.org/10.1038/leu.2014.332.

    Article  CAS  PubMed  Google Scholar 

  10. Beyar-Katz O, Lavi N, Ringelstein-Harlev S, Henig I, Yehudai-Ofir D, Haddad N, et al. Superior outcome of patients with favorable-risk acute myeloid leukemia using consolidation with autologous stem cell transplantation. Leuk Lymphoma. 2019;60:2449–56. https://doi.org/10.1080/10428194.2019.1594214.

    Article  CAS  PubMed  Google Scholar 

  11. Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, et al. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011;118:6037–42. https://doi.org/10.1182/blood-2011-07-370247.

    Article  CAS  PubMed  Google Scholar 

  12. Miyamoto T, Nagafuji K, Fujisaki T, Uchida N, Matsue K, Henzan H, et al. Prospective randomization of post-remission therapy comparing autologous peripheral blood stem cell transplantation versus high-dose cytarabine consolidation for acute myelogenous leukemia in first remission. Int J Hematol. 2018;107:468–77. https://doi.org/10.1007/s12185-017-2389-8.

    Article  CAS  PubMed  Google Scholar 

  13. Yoon JH, Kim HJ, Park SS, Jeon YW, Lee SE, Cho BS, et al. Clinical outcome of autologous hematopoietic cell transplantation in adult patients with acute myeloid leukemia: who may benefit from autologous hematopoietic cell transplantation? Biol Blood Marrow Transplant. 2017;23:588–97. https://doi.org/10.1016/j.bbmt.2017.01.070.

    Article  PubMed  Google Scholar 

  14. Jourdan E, Boissel N, Chevret S, Delabesse E, Renneville A, Cornillet P, et al. Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia. Blood. 2013;121:2213–23. https://doi.org/10.1182/blood-2012-10-462879.

    Article  CAS  PubMed  Google Scholar 

  15. Zhu HH, Zhang XH, Qin YZ, Liu DH, Jiang H, Chen H, et al. MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial. Blood. 2013;121:4056–62. https://doi.org/10.1182/blood-2012-11-468348.

    Article  CAS  PubMed  Google Scholar 

  16. Yin JA, O’Brien MA, Hills RK, Daly SB, Wheatley K, Burnett AK. Minimal residual disease monitoring by quantitative RT-PCR in core binding factor AML allows risk stratification and predicts relapse: results of the United Kingdom MRC AML-15 trial. Blood. 2012;120:2826–35. https://doi.org/10.1182/blood-2012-06-435669.

    Article  CAS  PubMed  Google Scholar 

  17. Sula M, Bacher U, Oppliger Leibundgut E, Mansouri Taleghani B, Novak U, Pabst T. Excellent outcome after consolidation with autologous transplantation in patients with core binding factor acute myeloid leukemia. Bone Marrow Transplant. 2019. https://doi.org/10.1038/s41409-019-0762-3.

    Article  PubMed  Google Scholar 

  18. Schuurhuis GJ, Heuser M, Freeman S, Bene MC, Buccisano F, Cloos J, et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2018;131:1275–91. https://doi.org/10.1182/blood-2017-09-801498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Walter RB, Othus M, Burnett AK, Lowenberg B, Kantarjian HM, Ossenkoppele GJ, et al. Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center. Leukemia. 2015;29:312–20. https://doi.org/10.1038/leu.2014.242.

    Article  CAS  PubMed  Google Scholar 

  20. Buckley SA, Wood BL, Othus M, Hourigan CS, Ustun C, Linden MA, et al. Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis. Haematologica. 2017;102:865–73. https://doi.org/10.3324/haematol.2016.159343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Araki D, Wood BL, Othus M, Radich JP, Halpern AB, Zhou Y, et al. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia: time to move toward a minimal residual disease-based definition of complete remission? J Clin Oncol. 2016;34:329–36. https://doi.org/10.1200/JCO.2015.63.3826.

    Article  Google Scholar 

  22. Zhou Y, Othus M, Araki D, Wood BL, Radich JP, Halpern AB, et al. Pre- and post-transplant quantification of measurable ('minimal’) residual disease via multiparameter flow cytometry in adult acute myeloid leukemia. Leukemia. 2016;30:1456–64. https://doi.org/10.1038/leu.2016.46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Allen C, Hills RK, Lamb K, Evans C, Tinsley S, Sellar R, et al. The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia. Leukemia. 2013;27:1891–901. https://doi.org/10.1038/leu.2013.186.

    Article  CAS  PubMed  Google Scholar 

  24. Duployez N, Marceau-Renaut A, Boissel N, Petit A, Bucci M, Geffroy S, et al. Comprehensive mutational profiling of core binding factor acute myeloid leukemia. Blood. 2016;127:2451–9. https://doi.org/10.1182/blood-2015-12-688705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chen W, Xie H, Wang H, Chen L, Sun Y, Chen Z, et al. Prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia: a systematic review and meta-analysis. PLoS ONE. 2016;11:e0146614. https://doi.org/10.1371/journal.pone.0146614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gorin NC, Labopin M, Frassoni F, Milpied N, Attal M, Blaise D, et al. Identical outcome after autologous or allogeneic genoidentical hematopoietic stem-cell transplantation in first remission of acute myelocytic leukemia carrying inversion 16 or t(8;21): a retrospective study from the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol. 2008;26:3183–8. https://doi.org/10.1200/jco.2007.15.3106.

    Article  PubMed  Google Scholar 

  27. Kuwatsuka Y, Miyamura K, Suzuki R, Kasai M, Maruta A, Ogawa H, et al. Hematopoietic stem cell transplantation for core binding factor acute myeloid leukemia: t(8;21) and inv(16) represent different clinical outcomes. Blood. 2009;113:2096–103. https://doi.org/10.1182/blood-2008-03-145862.

    Article  CAS  PubMed  Google Scholar 

  28. Eom KS, Kim HJ, Cho BS, Lee SE, Yahng SA, Yoon JH, et al. Equivalent outcome of autologous stem cell transplantation and reduced intensity conditioning stem cell transplantation in acute myeloid leukemia patients with t(8;21). Acta Haematol. 2015;133:266–76. https://doi.org/10.1159/000366261.

    Article  CAS  PubMed  Google Scholar 

  29. Mizutani M, Hara M, Fujita H, Aoki J, Kanamori H, Ohashi K, et al. Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR. Bone Marrow Transplant. 2016;51:645–53.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a Grant (2016-199) from the Asian Institute for Life Sciences, Seoul, Korea.

Author information

Authors and Affiliations

  1. Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea

    Eun-Ji Choi, Je-Hwan Lee, Jun-Hong Park, Han-Seung Park, Jung-Hee Lee & Kyoo-Hyung Lee

  2. Division of Hematology, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea

    Hawk Kim

  3. Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea

    Yunsuk Choi

  4. Department of Hematology and Oncology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea

    Won-Sik Lee & Sang-Min Lee

Authors
  1. Eun-Ji Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Je-Hwan Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hawk Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yunsuk Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Won-Sik Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sang-Min Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jun-Hong Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Han-Seung Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jung-Hee Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kyoo-Hyung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

CoOperative Study Group A for Hematology (COSAH)

Corresponding author

Correspondence to Je-Hwan Lee.

Ethics declarations

Conflict of interest

The authors report no potential conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 20 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Choi, EJ., Lee, JH., Kim, H. et al. Autologous hematopoietic cell transplantation following high-dose cytarabine consolidation for core-binding factor-acute myeloid leukemia in first complete remission: a phase 2 prospective trial. Int J Hematol 113, 851–860 (2021). https://doi.org/10.1007/s12185-021-03099-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-021-03099-6

Keywords

Search

Navigation