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Prospective phase II study of prophylactic low-dose azacitidine and donor lymphocyte infusions following allogeneic hematopoietic stem cell transplantation for high-risk acute myeloid leukemia and myelodysplastic syndrome


Thirty patients, with high-risk acute myeloid leukemia (AML, n = 20) or myelodysplastic syndrome (MDS, n = 10), were enrolled in a phase II trial entailing prophylactic post-transplant azacitidine (AZA) plus escalated doses of donor lymphocyte infusion (DLI). The median number of AZA cycles was 5 (1–12) with 10 patients (33%) completing the 12 projected cycles. DLI were performed in 17 patients: 5 received one DLI, 2 received 2 DLI and 8 received 3 infusions. AZA was well tolerated, but discontinued in 20 patients primarily due to graft-versus-host disease (GvHD) and relapse. The cumulative incidence (CI) of grade 1–3 acute GvHD was 31.5% and the chronic GvHD CI was 53% at 2 years. At a median follow-up of 49 months (27–63), 18 patients are alive. The overall and disease-free survivals are 65.5% (CI 95% = 48.2–82.8) at 2 years. Cause of death was mainly relapse for 9 patients. The median time to relapse was 7 months (2.5–58) and the cumulative incidence of relapse at 2 years was 27.6% (CI 95% = 12.8–44.6). These results confirm that AZA is well tolerated as a prophylactic treatment to reduce the risk of post-transplantation relapse and compared favorably to those of patients who receive no post-transplant maintenance.

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We acknowledge the technical and logistical support of V. Dehame. We also thank the patients for their time and support, the nursing staff for providing excellent care and the data managers. This study was supported by a grant from Celgene Ltd which provided azacitidine used in this study.

Author information

T.G. and M.M. designed the study; T.G., M.M., F.M. collected and analyzed clinical data and wrote the paper; F.M., B.G., T.G., M.M., analyzed the biological data; M.L., F.M. performed the statistical analysis; T.G., F.M., L.M., R.T., C.B., P.C., L.M., S.V., P.P., A.G., MT.R., A.H., N.M., P.M., I.Y.A., M.M. enrolled patients and all authors critically revised the manuscript for important intellectual content and approved the manuscript for publication. T.G. and F.M. contributed equally and share first authorship.

Conflict of interest

The authors declare that they have no conflict of interest.

Correspondence to Thierry Guillaume.

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Key words

  • azacitidine
  • donor lymphocyte infusion
  • relapse prevention
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