Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Low-dose 5-azacytidine as preventive therapy for relapse of AML and MDS following allogeneic HCT

Bone Marrow Transplantation volume 52, pages 918–921 (2017)Cite this article

Subjects

Relapse after allogeneic hematopoietic cell transplantation (allo-HCT) for AML or myelodysplastic syndrome (MDS) remains the main cause of treatment failure, and is associated with a poor prognosis and short survival regardless of salvage therapy.1

There are very few treatment modalities for this indication, including reduction/withdrawal of immunosuppressive therapy, chemotherapy with or without the infusion of donor lymphocytes, or a second allo-HCT, but results have been disappointing.2, 3 Therefore, there is an unmet need for novel and more effective therapies. This also applies to the setting of prevention of relapse. Limited data exist regarding the efficacy of 5-azacytidine in the setting of post-allograft relapses.4, 5 The data can be supported by experimental studies, showing that hypomethylating agents can induce functional suppressor function of regulatory T cells, mitigating GvHD without impairing GvL effect.6 We hypothesized that early administration of low-dose 5-azacytidine after allo-HCT might help reduce relapse in patients with high-risk myeloid malignancies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Bejanyan N, Weisdorf DJ, Logan BR, Wang HL, Devine SM, de Lima M et al. Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study. Biol Blood Marrow Transplant 2015; 21: 454–459.

    Article  PubMed  Google Scholar 

  2. Ruutu T, de Wreede LC, van Biezen A, Brand R, Mohty M, Dreger P et al. Second allogeneic transplantation for relapse of malignant disease: retrospective analysis of outcome and predictive factors by the EBMT. Bone Marrow Transplant 2015; 50: 1542–1550.

    Article  CAS  PubMed  Google Scholar 

  3. Bolanos-Meade J, Smith BD, Gore SD, McDevitt MA, Luznik L, Fuchs EJ et al. 5-azacytidine as salvage treatment in relapsed myeloid tumors after allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 2011; 17: 754–758.

    Article  CAS  PubMed  Google Scholar 

  4. Czibere A, Bruns I, Kroger N, Platzbecker U, Lind J, Zohren F et al. 5-Azacytidine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome who relapse after allo-SCT: a retrospective analysis. Bone Marrow Transplant 2010; 45: 872–876.

    Article  CAS  PubMed  Google Scholar 

  5. de Lima M, Giralt S, Thall PF, de Padua Silva L, Jones RB, Komanduri K et al. Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study. Cancer 2010; 116: 5420–5431.

    Article  CAS  PubMed  Google Scholar 

  6. Goodyear OC, Dennis M, Jilani NY, Loke J, Siddique S, Ryan G et al. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood 2012; 119: 3361–3369.

    Article  CAS  PubMed  Google Scholar 

  7. El Cheikh J, Otrock ZK, Qannus AA, Kharfan-Dabaja MA, Bazarbachi A . Risk-adapted approach to HLA-matched sibling hematopoietic cell allografting: impact of adjusting conditioning intensity and integrating post-transplant therapeutic interventions. Clin Lymphoma Myeloma Leuk 2016; 16: 304–310.

    Article  PubMed  Google Scholar 

  8. Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood 2014; 123: 3664–3671.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Schlenk RF . Post-remission therapy for acute myeloid leukemia. Haematologica 2014; 99: 1663–1670.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jabbour E, Giralt S, Kantarjian H, Garcia-Manero G, Jagasia M, Kebriaei P et al. Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia. Cancer 2009; 115: 1899–1905.

    Article  CAS  PubMed  Google Scholar 

  11. Tessoulin B, Delaunay J, Chevallier P, Loirat M, Ayari S, Peterlin P et al. Azacitidine salvage therapy for relapse of myeloid malignancies following allogeneic hematopoietic SCT. Bone Marrow Transplant 2014; 49: 567–571.

    Article  CAS  PubMed  Google Scholar 

  12. Schroeder T, Frobel J, Cadeddu RP, Czibere A, Dienst A, Platzbecker U 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 2013; 27: 1910–1913.

    Article  CAS  PubMed  Google Scholar 

  13. Craddock C, Jilani N, Siddique S, Yap C, Khan J, Nagra S et al. Tolerability and clinical activity of post-transplantation azacitidine in patients allografted for acute myeloid leukemia treated on the RICAZA trial. Biol Blood Marrow Transplant 2016; 22: 385–390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lubbert M, Bertz H, Wasch R, Marks R, Ruter B, Claus 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 2010; 45: 627–632.

    Article  CAS  PubMed  Google Scholar 

  15. Schroeder T, Rachlis E, Bug G, Stelljes M, Klein S, Steckel NK et al. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions—a retrospective multicenter analysis from the German Cooperative Transplant Study Group. Biol Blood Marrow Transplant 2015; 21: 653–660.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the nursing staff for providing excellent care for our patients and the physicians in the Hematology and Oncology division at the American University of Beirut Medical Center, and referring physicians from Lebanon and the Middle East region for their significant contributions and dedicated patients’ care.

Author contributions

JEC contributed to the study design, collected and analyzed the data, performed statistical analysis, provided clinical care, and wrote and revised the manuscript. R Massoud and EF collected the data and edited the manuscript. MC performed statistical analysis and commented on the manuscript. NK is in charge of the cell therapy facility that collected and delivered the blood cell grafts infused into patients included in this analysis, and commented on the manuscript. R Mahfouz performed the molecular analysis and edited the manuscript. MAK-D contributed to the study design, provided clinical care and edited the manuscript. AB designed the transplant program, contributed to the study design, recruited patients, provided clinical care and edited the manuscript.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Bone Marrow Transplantation Program, American University of Beirut Medical Center, Beirut, Lebanon

    J El-Cheikh, R Massoud, E Fares, M Charafeddine & A Bazarbachi

  2. Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon

    N Kreidieh & R Mahfouz

  3. Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center, Tampa, FL, USA

    M A Kharfan-Dabaja

Authors
  1. J El-Cheikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Massoud
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E Fares
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N Kreidieh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R Mahfouz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Charafeddine
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M A Kharfan-Dabaja
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Bazarbachi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J El-Cheikh.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El-Cheikh, J., Massoud, R., Fares, E. et al. Low-dose 5-azacytidine as preventive therapy for relapse of AML and MDS following allogeneic HCT. Bone Marrow Transplant 52, 918–921 (2017). https://doi.org/10.1038/bmt.2017.31

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2017.31

This article is cited by

Search

Advanced search

Quick links