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Salvage therapy with azacitidine increases regulatory T cells in peripheral blood of patients with AML or MDS and early relapse after allogeneic blood stem cell transplantation

Leukemia volume 27, pages 1910–1913 (2013)Cite this article

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Relapse after allogeneic blood stem cell transplantation (allo-SCT) is a major cause of treatment failure in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDL), with most recurrences occurring within the first year after transplantation.1 Donor lymphocyte infusions (DLI) are a well-established salvage therapy in this situation. In contrast to the success seen in chronic myeloid leukemia, their efficacy in AML or MDS is restricted to some patients. In addition, this benefit is also hampered by the substantial risk to induce severe graft-versus-host disease (GVHD), especially when DLI are administered early after transplantation.2 Recently, the combination of azacitidine (Aza) and DLI has proven to induce sustained remissions in about one-third of the patients with AML or MDS relapsing after allo-SCT.3, 4, 5 The incidence and severity of GVHD following this combined approach has been reported to be lower in comparison with historical data using DLI alone.3, 4, 5, 6, 7 As a potential mechanism, murine models have suggested that Aza upregulates the transcription factor FoxP3, thereby expanding CD4+ regulatory T cells (Tregs), which play an important role in the control of GVHD.8, 9, 10 This has also been recently shown in 17 patients with AML receiving Aza maintenance therapy following allo-SCT.11 Data on Tregs in patients who receive Aza and DLI to treat relapse are lacking so far.

We serially monitored CD3+CD4+CD25+FoxP3+ Tregs and lymphocyte subsets in the peripheral blood (PB) of 13 patients with AML (n=8) or MDS (n=5) who received Aza and DLI as first salvage therapy for relapse after allo-hematopoeitic SCT.

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Acknowledgements

We would like to thank the staff of the transplant unit of the Department of Hematology, Oncology and Clinical Immunology for excellent patient care, as well as Annemarie Koch for excellent laboratory work. This work was supported by Celgene Corporation, Germany, Leukämie Lymphom Hilfe Duesseldorf e.V., and Forschungskommission of the Heinrich Heine University Duesseldorf.

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Authors and Affiliations

  1. Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany

    T Schroeder, J Fröbel, R-P Cadeddu, A Czibere, A Dienst, R Fenk, U Germing, R Haas & G Kobbe

  2. University Hospital Carl Gustav Carus, Medizinische Klinik I, Dresden, Germany

    U Platzbecker

  3. Goethe University, Medizinische Klinik II, Frankfurt, Germany

    G Bug

  4. Department of Haematology, Charité Campus Virchow Klinikum, Oncology and Tumor Immunology, Berlin, Germany

    L Uharek

  5. University Hospital Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg, Germany

    N Kröger

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  1. T Schroeder
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  2. J Fröbel
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Corresponding author

Correspondence to T Schroeder.

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Competing interests

TS received financial travel support and honoraria from Celgene Corporation, Germany. UP received advisory fees, honoraria and research funding from Celgene Corporation, Germany. GB and RF received advisory fees, honoraria, travel grants and research funding from Celgene Corporation, Germany. UG received honoraria and research funding from Celgene Corporation, Germany. NK and GK received research funding from Celgene Corporation, Germany. The remaining authors declare no conflict of interest.

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Schroeder, T., Fröbel, J., Cadeddu, RP. et al. Salvage therapy with azacitidine increases regulatory T cells in peripheral blood of patients with AML or MDS and early relapse after allogeneic blood stem cell transplantation. Leukemia 27, 1910–1913 (2013). https://doi.org/10.1038/leu.2013.64

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