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.

  • Correspondence
  • Published:

Treosulfan-based double-alkylator conditioning in myelofibrosis: An Italian retrospective multicenter analysis

Bone Marrow Transplantation (2025)Cite this article

Subjects

To the Editor,

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the sole curative option for patients with myelofibrosis (MF), yet the choice of optimal conditioning regimen continues to be debated. Despite the employment of both reduced-intensity (RIC) and myeloablative (MAC) regimens, concerns regarding relapse and toxicity persist. Current 2024 ELN/EBMT guidelines lack definitive recommendations on conditioning intensity [1], underscoring the critical need for real-world data to inform clinical practice. Retrospective studies have suggested that conditioning mostly with single-alkylating agent treosulfan may be associated with a more favorable toxicity profile and improved outcomes compared to busulfan-based regimens in selected settings, including myelofibrosis (MF) [2]. However, a German multicenter study reported comparable outcomes between single-alkylator regimens using low-dose busulfan and treosulfan-based conditioning with doses up to 30 g/m² [3]. Recently, the use of thiotepa, fludarabine, and busulfan (TBF) as a conditioning regimen has been reported in a large EBMT registry study of patients with myelofibrosis, demonstrating reliable engraftment and effective disease control in selected populations [4]. However, TBF regimen has been linked to non-neglibible toxicity and high early NRM [4,5,6]. Substituting busulfan with treosulfan (TTF) may offer a more favorable toxicity profile, particularly in vulnerable patients, although its role in MF has not yet been systematically investigated. Thiotepa as second alkylating agent with potent immunosuppressive and antineoplastic activity may enhance disease control and promote engraftment especially in high-risk patients with adverse disease features. With the aim to assess the safety and efficacy of such combination we retrospectively analyzed 37 consecutive adult patients with chronic-phase MF who underwent allo-HSCT across four Italian transplant centers between 2017 and 2024. All patients received a conditioning regimen comprising thiotepa (5 mg/kg on day –6), treosulfan (10 g/m²/day on days –5 to –3), and fludarabine (30 mg/m²/day on days –5 to –2). Notably, 5 patients, treated at a single center, received a higher treosulfan dose of 12 g/m²/day and 3 patients received thiotepa at 10 mg/Kg on the same schedule. Median transplant conditioning index was 2 (range, 2-3). All patients provided informed consent for inclusion in the EBMT registry, as previously described [7].

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

Data availability

The dataset generated and analyzed during the current study is available from the corresponding author upon reasonable request.

References

  1. Kroger N, Bacigalupo A, Barbui T, Ditschkowski M, Gagelmann N, Griesshammer M, et al. Indication and management of allogeneic haematopoietic stem-cell transplantation in myelofibrosis: updated recommendations by the EBMT/ELN International Working Group. Lancet Haematol. 2024;11:e62–e74.

    Article  PubMed  Google Scholar 

  2. Robin M, Iacobelli S, Koster L, Passweg J, Avenoso D, Wilson KMO, et al. Treosulfan compared to busulfan in allogeneic haematopoietic stem cell transplantation for myelofibrosis: a registry-based study from the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transpl. 2024;59:928–35.

    Article  CAS  Google Scholar 

  3. Gagelmann N, Schuh C, Flossdorf S, Kunadt D, Stelljes M, Blau IW, et al. Impact of busulfan versus treosulfan dose intensity in myelofibrosis undergoing hematopoietic cell transplantation. Am J Hematol. 2024;99:1540–9.

    Article  CAS  PubMed  Google Scholar 

  4. Battipaglia G, Mauff K, Wendel L, Angelucci E, Mohty M, Arcese W, et al. Thiotepa-busulfan-fludarabine (TBF) conditioning regimen in patients undergoing allogeneic hematopoietic cell transplantation for myelofibrosis: an outcome analysis from the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transplant. 2021;56:1593–602.

    Article  CAS  PubMed  Google Scholar 

  5. Shouval R, Vega Y, Fein JA, Danylesko I, Shem Tov N, Yerushalmi R, et al. Allogeneic hematopoietic stem cell transplantation with fludarabine, busulfan, and thiotepa conditioning is associated with favorable outcomes in myelofibrosis. Bone Marrow Transpl. 2020;55:147–56.

    Article  CAS  Google Scholar 

  6. Memoli M, Paviglianiti A, Malard F, Battipaglia G, Brissot E, Mediavilla C, et al. Thiotepa-busulfan-fludarabine as a conditioning regimen for patients with myelofibrosis undergoing allogeneic hematopoietic transplantation: a single center experience. Leuk Lymphoma. 2021;62:419–27.

    Article  CAS  PubMed  Google Scholar 

  7. Polverelli N, Mauff K, Kroger N, Robin M, Beelen D, Beauvais D, et al. Impact of spleen size and splenectomy on outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis: A retrospective analysis by the chronic malignancies working party on behalf of European society for blood and marrow transplantation (EBMT). Am J Hematol. 2021;96:69–79.

    Article  CAS  PubMed  Google Scholar 

  8. Hernandez-Boluda JC, Mosquera-Orgueira A, Gras L, Koster L, Tuffnell J, Kroger N, et al. Use of machine learning techniques to predict poor survival after hematopoietic cell transplantation for myelofibrosis. Blood. 2025;145:3139–52.

    Article  CAS  PubMed  Google Scholar 

  9. Polverelli N, Hernandez-Boluda JC, Czerw T, Barbui T, D’Adda M, Deeg HJ, et al. Splenomegaly in patients with primary or secondary myelofibrosis who are candidates for allogeneic hematopoietic cell transplantation: a Position Paper on behalf of the Chronic Malignancies Working Party of the EBMT. Lancet Haematol. 2023;10:e59–e70.

    Article  CAS  PubMed  Google Scholar 

  10. Beelen DW, Stelljes M, Remenyi P, Wagner-Drouet EM, Dreger P, Bethge W, et al. Treosulfan compared with reduced-intensity busulfan improves allogeneic hematopoietic cell transplantation outcomes of older acute myeloid leukemia and myelodysplastic syndrome patients: Final analysis of a prospective randomized trial. Am J Hematol. 2022;97:1023–34.

    Article  CAS  PubMed  Google Scholar 

  11. Claudiani S, Marktel S, Piemontese S, Assanelli A, Lupo-Stanghellini MT, Carrabba M, et al. Treosulfan based reduced toxicity conditioning followed by allogeneic stem cell transplantation in patients with myelofibrosis. Hematol Oncol. 2016;34:154–60.

    Article  CAS  PubMed  Google Scholar 

  12. Chiusolo P, Bregante S, Giammarco S, Lamparelli T, Casarino L, Dominietto A, et al. Full donor chimerism after allogeneic hematopoietic stem cells transplant for myelofibrosis: The role of the conditioning regimen. Am J Hematol. 2021;96:234–40.

    Article  CAS  PubMed  Google Scholar 

  13. Patriarca F, Masciulli A, Bacigalupo A, Bregante S, Pavoni C, Finazzi MC, et al. Busulfan- or Thiotepa-Based Conditioning in Myelofibrosis: A Phase II Multicenter Randomized Study from the GITMO Group. Biol Blood Marrow Transpl. 2019;25:932–40.

    Article  CAS  Google Scholar 

  14. Fisher DAC, Fowles JS, Zhou A, Oh ST. Inflammatory Pathophysiology as a Contributor to Myeloproliferative Neoplasms. Front Immunol. 2021;12:683401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Polverelli N, Breccia M, Benevolo G, Martino B, Tieghi A, Latagliata R, et al. Risk factors for infections in myelofibrosis: role of disease status and treatment. A multicenter study of 507 patients. Am J Hematol. 2017;92:37–41.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: Nicola Polverelli, Annalisa Pitino, Irene Defrancesco.

  2. These authors jointly supervised this work: Graziella D’Arrigo, Mercedes Gori, Massimo Martino.

Authors and Affiliations

  1. Unit of Bone Marrow Transplantation and Cellular Therapies, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Nicola Polverelli, Irene Defrancesco & Caterina Zerbi

  2. Istituto di Fisiologia Clinica del Consiglio Nazionale delle Ricerche (CNR), Roma, Italy

    Annalisa Pitino & Mercedes Gori

  3. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy

    Giorgia Saporiti

  4. Unità di Ematologia, ASST Fatebenefratelli-Sacco Università degli Studi di Milano, Milan, Italy

    Francesco Onida

  5. Unità di Ematologia e TCS, Ospedale “Vito Fazzi”, Lecce, Italy

    Vincenzo Federico

  6. Unità di Ematologia e Centro Trapianti CSE, IRCCS Fondazione Casa Sollievo della Sofferenza San Giovanni Rotondo (FG), San Giovanni Rotondo, Italy

    Angelo Michele Carella & Dalila Salvatore

  7. Istituto di Fisiologia Clinica del Consiglio Nazionale delle Ricerche (CNR), Reggio Calabria, Italy

    Giovanni Tripepi & Graziella D’Arrigo

  8. Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano “Bianchi-Melacrino-Morelli”, Reggio Calabria, Italy

    Maria Caterina Micò, Giorgia Policastro, Gaetana Porto, Filippo Antonio Canale, Caterina Alati, Barbara Loteta & Massimo Martino

  9. U.O.C. Ematologia con trapianti di cellule staminali ematopoietiche (CSE) e Terapia Intensiva, AORN A. Cardarelli, Napoli, Italy

    Alessandra Picardi

Authors
  1. Nicola Polverelli
    View author publications

    Search author on:PubMed Google Scholar

  2. Annalisa Pitino
    View author publications

    Search author on:PubMed Google Scholar

  3. Irene Defrancesco
    View author publications

    Search author on:PubMed Google Scholar

  4. Giorgia Saporiti
    View author publications

    Search author on:PubMed Google Scholar

  5. Francesco Onida
    View author publications

    Search author on:PubMed Google Scholar

  6. Vincenzo Federico
    View author publications

    Search author on:PubMed Google Scholar

  7. Angelo Michele Carella
    View author publications

    Search author on:PubMed Google Scholar

  8. Dalila Salvatore
    View author publications

    Search author on:PubMed Google Scholar

  9. Giovanni Tripepi
    View author publications

    Search author on:PubMed Google Scholar

  10. Caterina Zerbi
    View author publications

    Search author on:PubMed Google Scholar

  11. Maria Caterina Micò
    View author publications

    Search author on:PubMed Google Scholar

  12. Giorgia Policastro
    View author publications

    Search author on:PubMed Google Scholar

  13. Gaetana Porto
    View author publications

    Search author on:PubMed Google Scholar

  14. Filippo Antonio Canale
    View author publications

    Search author on:PubMed Google Scholar

  15. Caterina Alati
    View author publications

    Search author on:PubMed Google Scholar

  16. Barbara Loteta
    View author publications

    Search author on:PubMed Google Scholar

  17. Alessandra Picardi
    View author publications

    Search author on:PubMed Google Scholar

  18. Graziella D’Arrigo
    View author publications

    Search author on:PubMed Google Scholar

  19. Mercedes Gori
    View author publications

    Search author on:PubMed Google Scholar

  20. Massimo Martino
    View author publications

    Search author on:PubMed Google Scholar

Contributions

N. Polverelli, A. Pitino, and I. Defrancesco contributed equally to the conception and writing of the manuscript. N. Polverelli and M. Martino designed the study. I. Defrancesco, G. Saporiti, F. Onida, V. Federico, A.M. Carella, D. Salvatore, A. Picardi, C. Zerbi, M.C. Micò, G. Policastro, G. Porto, F.A. Canale, C. Alati, and B. Loteta contributed to data acquisition and patient management. N. Polverelli, G. D’Arrigo, M. Gori, A. Pitino and G. Tripepi curated and analyzed the data, and performed statistical analyses. N. Polverelli, I. Defrancesco and M. Martino drafted the manuscript. All authors reviewed the manuscript and approved the final version for submission.

Corresponding authors

Correspondence to Nicola Polverelli or Massimo Martino.

Ethics declarations

Competing interests

The authors declare the following conflict of interest: NP received consultant fees from Medac Pharma.

Ethics approval and consent to participate

All procedures were performed in accordance with relevant guidelines and regulations. Informed consent for inclusion in the EBMT registry was obtained from all patients in accordance with EBMT policies.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Polverelli, N., Pitino, A., Defrancesco, I. et al. Treosulfan-based double-alkylator conditioning in myelofibrosis: An Italian retrospective multicenter analysis. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02791-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41409-025-02791-z

Search

Advanced search

Quick links