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Therapy

Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation

Abstract

The combination of azacitidine and donor lymphocyte infusions (DLI) as first salvage therapy for relapse after allogeneic transplantation (allo-HSCT) was studied in 30 patients with acute myeloid leukemia (AML; n=28) or myelodysplastic syndromes (MDS; n=2) within a prospective single-arm multicenter phase-II trial. Treatment schedule contained up to eight cycles azacitidine (100 mg/m2/day, days 1–5, every 28 days) followed by DLI (from 1–5 × 106 to 1–5 × 108 CD3+cells/kg) after every second azacitidine cycle. A median of three courses azacitidine (range 1–8) were administered, and 22 patients (73%) received DLI. Overall response rate was 30%, including seven complete remissions (CRs, 23%) and two partial remissions (7%). Five patients remain in CR for a median of 777 days (range 461–888). Patients with MDS or AML with myelodysplasia-related changes were more likely to respond (P=0.011), and a lower blast count (P=0.039) as well as high-risk cytogenetics (P=0.035) correlated with the likelihood to achieve CR. Incidence of acute and chronic graft-versus-host disease was 37% and 17%, respectively. Neutropenia and thrombocytopenia grade III/IV occurred during 65% and 63% of treatment cycles, while infections were the most common grade III/IV non-hematological toxicity. Azacitidine and DLI as salvage therapy is safe, induces long-term remissions and may become an alternative for patients with AML or MDS relapsing after allo-HSCT.

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Acknowledgements

This study was supported by research funding of Celgene Corporation, Germany to GK. This work was also supported by the Leukämie Lymphom Liga e. V. Duesseldorf, Germany and the Forschungskommision of the Heinrich-Heine-University, Duesseldorf, Germany. 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 Julia Fröbel, Ron-Patrick Cadeddu and Annemarie Koch for excellent laboratory work.

Author contributions

Conception and design: GK and AC. Provision of study materials or patients: NK, GB, UP, TL, LU, KR, CW, GK and TS. Collection and assembly of data: TS, GK, NK, GB, UP, TL, LU, KR and CW. Data analysis and interpretation: TS, GK, AC, RF, FZ and IB. Manuscript writing: TS, GK, RH and AC. Final approval of the manuscript: all authors.

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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 received advisory fees, honoraria, travel grants and research funding from Celgene Corporation, Germany. FZ is employed as medical director Millenium Pharmaceuticals, USA. RF received advisory fees, honoraria, travel grants and research funding from Celgene Corporation, Germany. UG received received honoraria and research funding from Celgene Corporation, Germany. NK received research funding from Celgene Corporation, Germany. The remaining authors declare no conflict of interest.

Additional information

Parts of this study have been presented at the 52nd American Society of Hematology (ASH) Annual Meeting, Orlando, FL, 4–7 December 2010, the BMT Tandem Meeting 2011, Honolulu, HI, 17–21 February 2011, the 37th Annual Meeting of the European Group for Bone and Marrow Transplantation (EBMT), Paris, France, 3–7 April 2011 and at the 53rd American Society of Hematology (ASH) Annual Meeting, San Diego, CA, 10–13 December 2011.

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Schroeder, T., Czibere, A., Platzbecker, U. et al. Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation. Leukemia 27, 1229–1235 (2013). https://doi.org/10.1038/leu.2013.7

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