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Allografting

Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting

Bone Marrow Transplantation volume 45, pages 627–632 (2010)Cite this article

Abstract

We have piloted a low-dose schedule of 5-azacytidine followed by donor lymphocyte infusions (DLIs) in patients with relapse of AML or chronic myelomonocytic leukemia (CMMoL) after allografting. Of the 26 patients (median age 62 years, range 28–75) with relapsed AML (n=24) or CMMoL (n=2), 11 (42%) had poor-risk cytogenetics. Twenty-three patients had received fludarabine-based reduced-toxicity conditioning regimens, and three had received conventional myeloablative conditioning. Patients received 5-azacytidine s.c., at a total daily dose of 100 mg, on days 1–3, to be followed by DLI on day 10, with the next course of treatment to be started on day 22. A total of 60 courses of 5-azacytidine were administered, with a median of 2 courses (range: 1–10). In 44 courses, 5-azacytidine was followed by DLI, and thus 19/26 (73%) patients received at least one course of this combined treatment. Clinically relevant neutropenic infections not associated with progressive disease developed in four patients, one of them succumbing to sepsis. Only two patients developed de novo acute GvHD after the combination of 5-azacytidine and DLI. Overall, 66% of the patients benefited from this treatment, with continued CRs achieved in 4 (16%) patients, lasting a median of 525 days (range: 450+ to 820+), and a 50% rate of temporary disease control with stable mixed chimerism (median duration 72 days). The median survival from the start of 5-azacytidine treatment was 136 days (range: 23 to 873+), with an estimated 2-year survival probability of 16%. In conclusion, this non-intensive outpatient regimen of 5-azacytidine followed by DLI is feasible, with a very low aGVHD rate. Objective responses, including continuous complete donor chimerism, occurred also in patients with poor-risk cytogenetics.

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Acknowledgements

We thank Irmgard Matt for excellent support with data acquisition; Sara Cohen, Ljudmilla Bogatyreva, Gabriele Ihorst, Claudia Schmoor and Thilo Hübsch for expert help with biostatistics; and Lydia Krause and Carol Cuerten for help with editing of this paper. We are grateful to the reviewers of the paper for providing many helpful suggestions.

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  1. B Rüter

    Present address: 2Current address: Merck Darmstadt, Darmstadt, Germany,

  2. R Claus

    Present address: 3Current address: Department of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany,

Authors and Affiliations

  1. Division Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany

    M Lübbert, H Bertz, R Wäsch, R Marks, B Rüter, R Claus & J Finke

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  1. M Lübbert
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Correspondence to M Lübbert or J Finke.

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Lübbert, M., Bertz, H., Wäsch, R. et al. Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting. Bone Marrow Transplant 45, 627–632 (2010). https://doi.org/10.1038/bmt.2009.222

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