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Efficacy and feasibility of cyclophosphamide combined with intermediate- dose or high-dose cytarabine for relapsed and refractory acute myeloid leukemia (AML)

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Approximately, 70 % of adult patients with de novo acute myeloid leukemia (AML) achieve a complete remission (CR) while 10–20 % of AML are refractory to induction chemotherapy. Furthermore, a significant proportion of AML patients in CR will relapse during or after consolidation treatment. There is no evidence for a standard salvage regimen and most centers use a combination of an anthracycline and cytarabine (AraC). The aim of this study was to investigate the impact of two age-adjusted regimens containing AraC and cyclophosphamide applied for the treatment of relapsed or refractory AML.

Patients and methods

We retrospectively analyzed 60 patients (24 male, 36 female; median age 56 years) with relapsed or refractory AML who were treated with a combination of AraC and cyclophosphamide monocentrically between October 2000 and January 2013. Two different protocols containing either high-dose (hAC) or intermediate-dose cytarabin (iAC) have been applied dependent on age and performance status.

Results

We demonstrate an overall response rate (CR + PR) induced by hAC and iAC of 56.7 %. Importantly, a complete remission rate (CR + CRp) of 52.2 % was found in patients who received the hAC regimen while only 8.8 % of patients achieved a CR following the iAC protocol (p < 0.001). The rate of refractory disease was 26.1 and 47.1 %, respectively. High-risk cytogenetics, i.e., a complex aberrant or monosomal karyotype had no effect on achievement of CR after hAC. In addition, there was no impact of activating FLT3 mutations on response to treatment according to the hAC regimen. In the cohort of patients treated with the iAC protocol, treatment-related mortality of 11.8 % within 60 days was observed but none of the patients who received the hAC regimen died within the first 2 months following chemotherapy. The toxicity profile was acceptable at both cytarabine dose levels. Importantly, 19 patients (82.6 %) of the hAC cohort underwent allogeneic hematopoietic stem cell transplantation (HSCT) as consecutive treatment.

Conclusion

The hAC regimen represents a promising therapeutic approach to induce a second CR in younger patients with relapsed or refractory AML prior to HSCT without using anthracyclines.

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Acknowledgments

This work was supported by a grant from the Deutsche José Carreras Leukämie-Stiftung (Project R11/03).

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None.

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Author notes

  1. Peter Fix

    Present address: Abteilung Internistische Onkologie und Hämatologie, Zentralklinik Bad Berka, Bad Berka, Germany

Authors and Affiliations

  1. Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany

    Ulf Schnetzke, Baerbel Spies-Weisshart, Karin Schrenk, Hans-Joerg Fricke, Paul La Rosée, Andreas Hochhaus & Sebastian Scholl

  2. Institut für Humangenetik, Universitätsklinikum Jena, Jena, Germany

    Anita Glaser

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  1. Ulf Schnetzke
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Correspondence to Sebastian Scholl.

Additional information

Ulf Schnetzke and Peter Fix have contributed equally to this work.

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Schnetzke, U., Fix, P., Spies-Weisshart, B. et al. Efficacy and feasibility of cyclophosphamide combined with intermediate- dose or high-dose cytarabine for relapsed and refractory acute myeloid leukemia (AML). J Cancer Res Clin Oncol 140, 1391–1397 (2014). https://doi.org/10.1007/s00432-014-1666-7

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