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Allogeneic hematopoietic cell transplantation with double alkylating agents containing reduced-intensity conditioning for patients ⩾60 years with advanced AML/MDS

Leukemia volume 30, pages 2426–2429 (2016)Cite this article

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Patients ⩾60 years with acute myeloblastic leukemia (AML)/myelodysplastic syndrome (MDS) have a poor chance of long-time survival after conventional treatment.1 Overall, only 30% of these patients receive intensive chemotherapy,2 resulting in a 2-year overall survival (OS) of 10 to 27%.3 Allogeneic hematopoietic cell transplantation (alloHCT) is potentially curative and reduced-intensity conditioning regimens in patients older than 60 years show encouraging results.4, 5 However, long-term outcomes data regarding patients with active disease are sparse.

Here, we report on detailed multivariable analyses of a phase II prospective study in 250 consecutive patients ⩾60 years, median age 66 years (range 60–77), transplanted from unrelated (n=186) or related (n=64) donors with peripheral blood stem cells (n=243) or bone marrow (n=7), with a double alkylating agent containing reduced-intensity conditioning regimen (fludarabine, bis-chlorethyl-nitroso-urea/carmustine, melphalan; FBM), at the Freiburg University Medical Center between 1999 and 2012. Two hundred and four patients (81.6%) had active AML/MDS and 46 patients (18.4%) had early disease at the time of alloHCT, defined as complete remission (CR)1/2 (n=39) and MDS refractory anemia (n=7; Table 1). Graft-versus-host disease (GvHD) prophylaxis mainly consisted of cyclosporine A (98% of patients) starting at day −3 at a dose of 2.5 mg/kg twice a day (trough level 250–350 ng/ml) in combination with several other immunosuppressive agents. The combination partners changed over time including methotrexate (15 mg/m2 day +1, 10 mg/m2 days +3 and +6), mycophenolate mofetil 2 × 1000 mg per day (n=63; MMF; Cell-Cept, Roche, Basel, Switzerland) or alemtuzumab (n=181; Campath, MabCampath, Genzyme, Neu-Isenburg, Germany) in decreasing doses over time, 40–10 mg (total dose).6 In case of unrelated-donor transplantation, patients not receiving alemtuzumab received anti-T-lymphocyte-globulin (ATG-F, Neovii, Gräfelfing, Germany).7 Standard supportive care was given as described previously.6 The study was registered at the Freiburg ethics committee, all patients signed informed consent to alloHCT and to prospective data collection, and were treated according to the declaration of Helsinki.

Table 1 Patient characteristics
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Acknowledgements

We thank Carole Cürten/Philip Sander for language and Irmgard Matt for data management; Professors Bentz, Brugger, Jakob, Köchling and Mezger for patient referrals; Drs Schnitzler/Müller for data preparation; the nurses and doctors of the Löhr ward for patient care; and finally, Professors Mertelsmann and Duyster for their continuous support.

Author contributions

JF designed the study and wrote the paper, HB analyzed the data and wrote the paper, KO performed the statistical analysis; all authors contributed data and approved the manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine, Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Freiburg, Germany

    H Bertz, M Lübbert, R Zeiser, R Wäsch, R Marks & J Finke

  2. Institute for Medical Biometry and Statistics, Freiburg University, Freiburg, Germany

    K Ohneberg

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  1. H Bertz
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  7. J Finke
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Corresponding author

Correspondence to H Bertz.

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Competing interests

HB had received lecture fee from Celgene, ML had received lecture fee and travel support from Celgene, RZ was funded by a Heisenberg Professorship by the German Research Foundation (DFG) and JF had received lecture fee and travel support from Neovii; KO, RW and RM have nothing to declare.

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Bertz, H., Lübbert, M., Ohneberg, K. et al. Allogeneic hematopoietic cell transplantation with double alkylating agents containing reduced-intensity conditioning for patients ⩾60 years with advanced AML/MDS. Leukemia 30, 2426–2429 (2016). https://doi.org/10.1038/leu.2016.248

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