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Allogeneic hematopoietic cell transplantation in patients with CALR-mutated myelofibrosis: a study of the Chronic Malignancies Working Party of EBMT

Bone Marrow Transplantation volume 58, pages 1357–1367 (2023)Cite this article

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Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is curative for myelofibrosis (MF) but assessing risk-benefit in individual patients is challenging. This complexity is amplified in CALR-mutated MF patients, as they live longer with conventional treatments compared to other molecular subtypes. We analyzed outcomes of 346 CALR-mutated MF patients who underwent allo-HCT in 123 EBMT centers between 2005 and 2019. After a median follow-up of 40 months, the estimated overall survival (OS) rates at 1, 3, and 5 years were 81%, 71%, and 63%, respectively. Patients receiving busulfan-containing regimens achieved a 5-year OS rate of 71%. Non-relapse mortality (NRM) at 1, 3, and 5 years was 16%, 22%, and 26%, respectively, while the incidence of relapse/progression was 11%, 15%, and 17%, respectively. Multivariate analysis showed that older age correlated with worse OS, while primary MF and HLA mismatched transplants had a near-to-significant trend to decreased OS. Comparative analysis between CALR- and JAK2-mutated MF patients adjusting for confounding factors revealed better OS, lower NRM, lower relapse, and improved graft-versus-host disease-free and relapse-free survival (GRFS) in CALR-mutated patients. These findings confirm the improved prognosis associated with CALR mutation in allo-HCT and support molecular profiling in prognostic scoring systems to predict OS after transplantation in MF.

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Fig. 1: Main outcomes in 346 patients with CALR-mutated myelofibrosis undergoing allogeneic hematopoietic cell transplantation.
Fig. 2: Main outcomes according to molecular subtype in 1272 patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation.
Fig. 3: Overall survival in 1272 patients with primary or post-essential thrombocythemia myelofibrosis undergoing allogeneic hematopoietic cell transplantation according to molecular subtype.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Author information

Authors and Affiliations

  1. Hospital Clínico Universitario-INCLIVA, University of Valencia, Valencia, Spain

    Juan Carlos Hernández-Boluda

  2. EBMT Statistical Unit, Leiden, the Netherlands

    Diderik-Jan Eikema

  3. EBMT Leiden Study Unit, Leiden, the Netherlands

    Linda Koster

  4. University Hospital Eppendorf, Hamburg, Germany

    Nicolaus Kröger

  5. Hôpital Saint-Louis, APHP, Université de Paris Cité, Paris, France

    Marie Robin

  6. University Medical Center, Utrecht, the Netherlands

    Moniek de Witte

  7. University of Freiburg and Medical Faculty, Freiburg, Germany

    Jürgen Finke

  8. University of Milan and ASST Papa Giovanni XXIII, Bergamo, Italy

    Maria Chiara Finazzi

  9. Erasmus MC Cancer Institute, Rotterdam, the Netherlands

    Annoek Broers

  10. Olomouc University Hospital, Olomouc, Czech Republic

    Ludek Raida

  11. Radboud University Medical Centre, Nijmegen, the Netherlands

    Nicolaas Schaap

  12. Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Dipartamento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico A, Gemelli IRCCS, Rome, Italy

    Patrizia Chiusolo

  13. Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Clinic and Policlinic for Internal Medicine III, Munich, Germany

    Mareike Verbeek

  14. University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

    Carin L. E. Hazenberg

  15. Institute of Hematology and Transfusion Medicine, Warsaw, Poland

    Kazimierz Halaburda

  16. First State Pavlov Medical University of St. Petersburg, St. Petersburg, Russian Federation

    Aleksandr Kulagin

  17. Centre Hospitalier Lyon Sud, Lyon, France

    Hélène Labussière-Wallet

  18. Oslo University Hospital, Hematology dep, Stem cell transplantation and Institute for Clinical Medicine, University of Oslo, Oslo, Norway

    Tobias Gedde-Dahl

  19. BMT-Unit, Internal Medicine I, Medical University of Vienna, Vienna, Austria

    Werner Rabitsch

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

    Kavita Raj & Donal P. McLornan

  21. Central Clinical Hospital, The Medical University of Warsaw, Warsaw, Poland

    Joanna Drozd-Sokolowska

  22. Hematology Department, Federico II University of Naples, Naples, Italy

    Giorgia Battipaglia

  23. Unit of Blood Diseases and Stem Cell Transplant - ASST Spedali Civili - University of Brescia, Brescia, Italy

    Nicola Polverelli

  24. Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice, Poland

    Tomasz Czerw

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

    Ibrahim Yakoub-Agha

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  1. Juan Carlos Hernández-Boluda
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Contributions

JCHB, DJE, GB, NP, TC, IYA and DMcL were involved in study design, analysis and writing of the paper. LK was the data manager. All other co-authors contributed data to the study, critically revised the paper and approved the submitted and final version.

Corresponding authors

Correspondence to Juan Carlos Hernández-Boluda or Donal P. McLornan.

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The authors declare no competing interests.

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This retrospective study was approved by the Chronic Malignancies Working Party (CMWP) of EBMT.

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Informed consent for inclusion in the EBMT registry was obtained in all patients.

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Hernández-Boluda, J.C., Eikema, DJ., Koster, L. et al. Allogeneic hematopoietic cell transplantation in patients with CALR-mutated myelofibrosis: a study of the Chronic Malignancies Working Party of EBMT. Bone Marrow Transplant 58, 1357–1367 (2023). https://doi.org/10.1038/s41409-023-02094-1

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