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Single-agent 5-azacytidine as post-transplant maintenance in high-risk myeloid malignancies undergoing allogeneic hematopoietic cell transplantation

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Abstract

Relapse is a major cause of treatment failure after allogeneic hematopoietic cell transplantation (allo-HCT) in myeloid malignancies. Additional strategies have been devised to further maximize the immunologic effect of allo-HCT, notably through maintenance therapy with hypomethylating agents such as 5-azacytidine (AZA). We conducted a single-center retrospective study to investigate the efficacy of AZA after allo-HCT for high-risk myeloid malignancies. All patients transplanted between Jan 2014 and Sept 2019 for high-risk acute myeloid leukemia (n = 123), myelodysplastic syndrome (n = 51), or chronic myelomonocytic leukemia (n = 11) were included. Patients who died, relapsed, or developed grade ≥ 2 acute graft-versus-host disease before day + 60 were excluded, as well as those who were eligible for anti-FMS-like tyrosine kinase 3 maintenance. Of the 185 included patients, 65 received AZA while 120 did not. Median age at transplant was 59 years; 51.9% of patients were males. The median follow-up was 24 months for both groups. Regarding main patient characteristics and transplantation modalities, the two groups were comparable. In multivariate analyses, there were no significant differences between the two groups in terms of 2-year cumulative incidence of relapse (HR = 1.19; 95% confidence interval (CI) 0.67–2.12; p = 0.55), overall survival (HR = 0.62; 95%CI 0.35–1.12; p = 0.12) and event-free survival (HR = 0.97; 95%CI 0.60–1.58; p = 0.91) rates. In conclusion, single-agent AZA does not appear to be an optimal drug for preventing post-transplant relapse in patients with high-risk myeloid malignancies. This study highlights the need for prospective studies of alternative therapies or combination approaches in the post-transplant setting.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

The authors would like to thank Micheline Karam, the study coordinator, for collecting and checking data on-site. The authors wish to acknowledge all staff for their dedication and involvement in the daily care of the patients. The authors thank Rachel Tipton and Ryan Mikati for proofreading the manuscript. Ibrahim Yakoub-Agha would like to thank the “association Capucine” for their support in his research.

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Authors and Affiliations

  1. UAM Allogreffe de Cellules Souches Hématopoïétiques, Department of Hematology, CHU Lille – Hôpital Huriez, Univ. Lille, 1 rue Michel Polonovski, F-59037, Lille Cedex, France

    Kevin-James Wattebled, Valérie Coiteux, Léonardo Magro, Micha Srour, Paul Chauvet, Bruno Quesnel, Ibrahim Yakoub-Agha & David Beauvais

  2. ULR 2694 - METRICS: Évaluation Des Technologies de Santé Et Des Pratiques Médicales, CHU Lille, Univ. Lille, Lille, France

    Elodie Drumez & Alain Duhamel

  3. Department of Biostatistics, CHU Lille, Lille, France

    Elodie Drumez & Alain Duhamel

  4. Inserm UMR1277 CNRS UMR9020 – CANTHER, Lille, France

    Bruno Quesnel

  5. Univ. Lille, CHU Lille, Inserm, Infinite, U1286, Lille, France

    Ibrahim Yakoub-Agha & David Beauvais

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  1. Kevin-James Wattebled
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  2. Elodie Drumez
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Contributions

KJW, IYA, and DB designed the study. BQ and IYA supervised the study. VC, LM, MS, and PC collected clinical data. ED and AD performed data analysis. KJW and DB analyzed data and wrote the initial manuscript. All authors read and approved the final manuscript.

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Correspondence to David Beauvais.

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Informed consent was obtained from all patients for being included in the study. This study was led according to the Declaration of Helsinki.

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Wattebled, KJ., Drumez, E., Coiteux, V. et al. Single-agent 5-azacytidine as post-transplant maintenance in high-risk myeloid malignancies undergoing allogeneic hematopoietic cell transplantation. Ann Hematol 101, 1321–1331 (2022). https://doi.org/10.1007/s00277-022-04821-y

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