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Combination of fludarabine, amsacrine, and cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia

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Abstract

Sequential use of chemotherapy and reduced-intensity conditioning (RIC) with allogeneic stem cell transplantation (SCT) has been proposed to improve the treatment outcomes in patients with high-risk acute myeloid leukemia (AML). Here, we present our experience with this procedure in a cohort of 60 AML patients with primary induction failure (n = 9); early, refractory, or ≥ second relapse (n = 41); or unfavorable cytogenetics (n = 10). A combination of fludarabine (30 mg/m2/day), cytarabine (2 g/m2/day), and amsacrine (100 mg/m2/day) for 4 days was used. After 3 days of rest, RIC was carried out, consisting of 4 Gy total body irradiation, antithymocyte globulin (ATG-Fresenius), and cyclophosphamide (fludarabine, amsacrine, and cytarabine (FLAMSA)-RIC protocol). Prophylactic donor lymphocyte infusions (pDLIs) were given in patients with complete remission (CR) and without evidence of graft-versus-host disease ≥120 days after SCT. The median time of neutrophil engraftment was 17 days. CR was achieved in 47 of 60 patients (78 %). Eleven patients received pDLIs resulting in long-term CR in eight of them. Non-relapse mortality after 1 and 3 years was 25 and 28 %, respectively. With a median follow-up of 37 months (range, 10–69), 3-year overall survival and 3-year progression-free survival were 42 and 33 %, respectively. In a multivariate analysis, dose of CD34(+) cells >5 × 106/kg (p = 0.005; hazard ratio (HR) = 0.276), remission of AML before SCT (p = 0.044; HR = 0.421), and achievement of complete chimerism after SCT (p = 0.001; HR = 0.205) were significant factors of better overall survival. The use of the FLAMSA-RIC protocol in suitable high-risk AML patients results in a long-term survival rate of over 40 %.

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Acknowledgments

The work was supported in part by Research Grants MSMT CR CZ.1.05/1.1.00/02.0068 (CEITEC), MSMT CR CZ.1.07/2.3.00/20.0045 (SuPReMMe), and by the Czech Leukemia Study Group – for Life (CELL), and by MH CZ – DRO (FNBr, 65269705).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University, Jihlavska 20, 625 00, Brno, Czech Republic

    Marta Krejci, Michael Doubek, Yvona Brychtova, Zdenek Racil, Milan Navratil, Miroslav Tomiska, Ondrej Horky, Sarka Pospisilova & Jiri Mayer

  2. Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00, Brno, Czech Republic

    Michael Doubek, Sarka Pospisilova & Jiri Mayer

  3. Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic

    Jaroslav Dusek

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  1. Marta Krejci
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  2. Michael Doubek
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  9. Sarka Pospisilova
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  10. Jiri Mayer
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Correspondence to Marta Krejci.

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Krejci, M., Doubek, M., Dusek, J. et al. Combination of fludarabine, amsacrine, and cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia. Ann Hematol 92, 1397–1403 (2013). https://doi.org/10.1007/s00277-013-1790-5

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