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.

  • Article
  • Published:

Sequential vs myeloablative vs reduced intensity conditioning for patients with myelodysplastic syndromes with an excess of blasts at time of allogeneic haematopoietic cell transplantation: a retrospective study by the chronic malignancies working party of the EBMT

Bone Marrow Transplantation volume 59, pages 224–231 (2024)Cite this article

Subjects

Abstract

The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5–65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45–56%) and relapse free survival (RFS) 45% (95% CI 40–51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.

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

Fig. 1: OS, RFS, CIR and NRM for MAC, Seq and RIC protocols.
Fig. 2: Chronic GVHD and mortality not related to GVHD for MAC, Seq and RIC protocols.
Fig. 3: GVHD free, relapse free survival per conditioning protocol in MDS patients after allo-HCT.
Fig. 4: Predicted survival probabilities based on a Cox model during the first 5 years after allo-HCT for a reference patient receiving either MAC, RIC or Seq conditioning.

Similar content being viewed by others

Data availability

The final analysis dataset will be available upon specific request to the working party chair.

References

  1. Garcia‐Manero G, Chien KS, Montalban‐Bravo G. Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management. Am J Hematol. 2020;95:1399–420.

    Article  PubMed  Google Scholar 

  2. Kröger N. Induction, bridging, or straight ahead: the ongoing dilemma of allografting in advanced myelodysplastic syndrome. Biol Blood Marrow Transpl. 2019;25:e247–9.

    Article  Google Scholar 

  3. Saure C, Schroeder T, Zohren F, Groten A, Bruns I, Czibere A, et al. Upfront allogeneic blood stem cell transplantation for patients with high-risk myelodysplastic syndrome or secondary acute myeloid leukemia using a FLAMSA-based high-dose sequential conditioning regimen. Biol Blood Marrow Transpl. 2012;18:466–72.

    Article  Google Scholar 

  4. Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb H-J. Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol. 2005;23:5675–87.

    Article  PubMed  Google Scholar 

  5. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–88.

    Article  CAS  PubMed  Google Scholar 

  6. Arber DA, Orazi A, Hasserjian R, Borowitz MJ, Beau MM, Bloomfield CD, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–406.

    Article  CAS  PubMed  Google Scholar 

  7. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2009;15:1628–33.

    Article  Google Scholar 

  9. Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996;17:343–6.

    Article  CAS  PubMed  Google Scholar 

  10. Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, et al. Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2017;35:1154–61.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kröger N, Iacobelli S, Franke G-N, Platzbecker U, Uddin R, Hübel K, et al. Dose-reduced versus standard conditioning followed by allogeneic stem-cell transplantation for patients with myelodysplastic syndrome: a prospective randomized Phase III study of the EBMT (RICMAC Trial). J Clin Oncol. 2017;35:2157–64.

    Article  PubMed  Google Scholar 

  12. Craddock C, Jackson A, Loke J, Siddique S, Hodgkinson A, Mason J, et al. Augmented reduced-intensity regimen does not improve postallogeneic transplant outcomes in acute myeloid leukemia. J Clin Oncol. 2021;39:768–78.

    Article  CAS  PubMed  Google Scholar 

  13. Hourigan CS, Dillon LW, Gui G, Logan BR, Fei M, Ghannam J, et al. Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease. J Clin Oncol. 2020;38:1273–83.

    Article  CAS  PubMed  Google Scholar 

  14. Christopeit M, Badbaran A, Alawi M, Zabelina T, Zeck G, Wolschke C, et al. Correlation of somatic mutations with outcome after FLAMSA-busulfan sequential conditioning and allogeneic stem cell transplantation in patients with myelodysplastic syndromes. Eur J Haematol. 2016;97:288–96.

    Article  CAS  PubMed  Google Scholar 

  15. Ciurea SO, Chilkulwar A, Saliba RM, Chen J, Rondon G, Patel KP, et al. Prognostic factors influencing survival after allogeneic transplantation for AML/MDS patients with TP53 mutations. Blood. 2018;131:2989–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lindsley RC, Saber W, Mar BG, Redd R, Wang T, Haagenson MD, et al. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N. Engl J Med. 2017;376:536–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Forcade E, Chevret S, Finke J, Ehninger G, Beelen D, et al. Impact of in vivo T-cell depletion in patients with myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplant: a registry study from the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transpl. 2022;57:768–74.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Kings College Hospital NHS Foundation Trust, London, UK

    V. Potter

  2. EBMT Statistical Unit, Leiden, Netherlands

    L. Gras

  3. EBMT Leiden Study Unit, Leiden, Netherlands

    L. Koster

  4. University Hospital Eppendorf, Hamburg, Germany

    N. Kroger

  5. Universitaetsklinikum Dresden, Dresden, Germany

    K. Sockel

  6. Hannover Medical School, Hannover, Germany

    A. Ganser

  7. University of Freiburg, Freiburg, Germany

    J. Finke

  8. Centre Hospitalier Lyon Sud, Lyon, France

    H. Labussiere-Wallet

  9. Saint-Louis Hospital, BMT Unit, Paris, France

    R. Peffault de Latour & M. Robin

  10. Medicana International Hospital Istanbul, Istanbul, Turkey

    Y. Koc

  11. HUCH Comprehensive Cancer Center, Helsinki, Finland

    U. Salmenniemi

  12. Bone Marrow Transplant Unit L, 4043, Copenhagen, Denmark

    L. Smidstrup Friis

  13. Charles University Hospital, Pilsen, Czech Republic

    P. Jindra

  14. University Hospital Essen, Dusseldorf, Germany

    T. Schroeder

  15. Klinikum Grosshadern, Munich, Germany

    J. Tischer

  16. Demiroglu Bilim University Istanbul Florence Nightingale Hospital, Stanbul, Turkey

    M. Arat

  17. Hospital Regional de Málaga, Málaga, Spain

    M. Pascual Cascon

  18. Leiden University Medical Center, Dept of Biomedical Data Sciences, Leiden, Netherlands

    L. C. de Wreede

  19. Department of Haematology, Trinity College Dublin, St. James’s Hospital, Dublin, Ireland

    P. Hayden

  20. University College London Hospitals NHS Trust, London, UK

    K. Raj & D. P. McLornan

  21. Medical University of Warsaw, Warsaw, Poland

    J. Drozd-Sokolowska

  22. University of Cologne, Cologne, Germany

    C. Scheid

  23. CHU de Lille, Univ Lille, INSERM U1286, Infinite, 59000, Lille, France

    I. Yakoub-Agha

Authors
  1. V. Potter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Gras
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Koster
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Kroger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Sockel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Ganser
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Finke
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H. Labussiere-Wallet
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R. Peffault de Latour
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Y. Koc
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. U. Salmenniemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. L. Smidstrup Friis
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. P. Jindra
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. T. Schroeder
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. J. Tischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. M. Arat
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. M. Pascual Cascon
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. L. C. de Wreede
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. P. Hayden
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. K. Raj
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. J. Drozd-Sokolowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. C. Scheid
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. D. P. McLornan
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. M. Robin
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. I. Yakoub-Agha
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

VP conceived and designed the study proposal, acquired data, interpreted results, drafted and revised manuscript, and approved final version. MR, DM, IYA conceived and designed the study proposal, interpreted results, revised manuscript, and approved final version. LG, LK, LdW acquired data, completed statistical analysis, interpreted results and approved final version. NK, KS, AG, JF, HLW, RPdL, YK, US, LSF, PJ, TS, JT, MA, MPC, PH, KR, JDS, CS acquired data, interpreted results and approved final version.

Corresponding author

Correspondence to V. Potter.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Potter, V., Gras, L., Koster, L. et al. Sequential vs myeloablative vs reduced intensity conditioning for patients with myelodysplastic syndromes with an excess of blasts at time of allogeneic haematopoietic cell transplantation: a retrospective study by the chronic malignancies working party of the EBMT. Bone Marrow Transplant 59, 224–231 (2024). https://doi.org/10.1038/s41409-023-02111-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-023-02111-3

Search

Advanced search

Quick links