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Outcomes following second allogeneic haematopoietic cell transplantation in patients with myelofibrosis: a retrospective study of the Chronic Malignancies Working Party of EBMT

Bone Marrow Transplantation volume 56, pages 1944–1952 (2021)Cite this article

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Abstract

Therapeutic management of patients with primary or secondary myelofibrosis (MF) who experience relapse or graft failure following allogeneic haematopoietic cell transplantation (allo-HCT) remains heterogeneous. We retrospectively analyzed 216 patients undergoing a second allo-HCT for either relapse (56%) or graft failure (31%) between 2010 and 2017. Median age was 57.3 years (range 51–63). The same donor as for the first allo-HCT was chosen in 66 patients (31%) of whom 19 received an HLA-identical sibling donor, whereas a different donor was chosen for 116 patients (54%). Median follow-up was 40 months. Three-year overall survival (OS) and relapse-free survival (RFS) were 42% and 39%, respectively. Three-year non-relapse mortality (NRM) and relapse rates were 36% and 25%, respectively. Grade II-IV and III-IV acute GVHD occurred in 25% and 11% of patients, respectively, and the 3-year incidence of chronic GVHD was 33% including 14% for extensive grade. Graft-failure incidence at 1 year was 14%. In conclusion, our data suggest that a second allo-HCT is a potential option for patients failing first allo-HCT for MF albeit careful patient assessment is fundamental to identify individual patients who could benefit from this approach.

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Fig. 1
Fig. 2: Cumulative incidence of relapse (lower plot) and non-relapse mortality (upper plot).
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References

  1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.

    Article  CAS  Google Scholar 

  2. Tefferi A. Primary myelofibrosis: 2019 update on diagnosis, risk-stratification and management. Am J Hematol. 2018;93:1551–60.

    Article  Google Scholar 

  3. Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113:2895–901.

    Article  CAS  Google Scholar 

  4. Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115:1703–8.

    Article  CAS  Google Scholar 

  5. Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, et al. DIPSS plus: a refined dynamic international prognostic scoring system for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. JCO. 2011;29:392–7.

    Article  Google Scholar 

  6. Guglielmelli P, Lasho TL, Rotunno G, Mudireddy M, Mannarelli C, Nicolosi M, et al. MIPSS70: mutation-enhanced international prognostic score system for transplantation-age patients with primary myelofibrosis. JCO. 2018;36:310–8.

    Article  CAS  Google Scholar 

  7. Tefferi A, Guglielmelli P, Nicolosi M, Mannelli F, Mudireddy M, Bartalucci N, et al. GIPSS: genetically inspired prognostic scoring system for primary myelofibrosis. Leukemia. 2018;32:1631–42.

    Article  Google Scholar 

  8. Gowin K, Coakley M, Kosiorek H, Mesa R. Discrepancies of applying primary myelofibrosis prognostic scores for patients with post polycythemia vera/essential thrombocytosis myelofibrosis. Haematologica. 2016;101:e405–6.

    Article  Google Scholar 

  9. Barbui T, Tefferi A, Vannucchi AM, Passamonti F, Silver RT, Hoffman R, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leuk. 2018;32:1057–69.

    Article  Google Scholar 

  10. Rago A, Latagliata R, Montanaro M, Montefusco E, Andriani A, Crescenzi SL, et al. Hemoglobin levels and circulating blasts are two easily evaluable diagnostic parameters highly predictive of leukemic transformation in primary myelofibrosis. Leuk Res. 2015;39:314–7.

    Article  CAS  Google Scholar 

  11. Caramazza D, Begna KH, Gangat N, Vaidya R, Siragusa S, Van Dyke DL, et al. Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients. Leukemia. 2011;25:82–8.

    Article  CAS  Google Scholar 

  12. Tefferi A, Nicolosi M, Mudireddy M, Lasho TL, Gangat N, Begna KH, et al. Revised cytogenetic risk stratification in primary myelofibrosis: analysis based on 1002 informative patients. Leukemia. 2018;32:1189–99.

    Article  Google Scholar 

  13. Guglielmelli P, Lasho TL, Rotunno G, Score J, Mannarelli C, Pancrazzi A, et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia. 2014;28:1804–10.

    Article  CAS  Google Scholar 

  14. Kröger N, Panagiota V, Badbaran A, Zabelina T, Triviai I, Araujo Cruz MM, et al. Impact of molecular genetics on outcome in myelofibrosis patients after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2017;23:1095–101.

    Article  Google Scholar 

  15. McLornan DP, Yakoub-Agha I, Robin M, Chalandon Y, Harrison CN, Kroger N. State-of-the-art review: allogeneic stem cell transplantation for myelofibrosis in 2019. Haematologica. 2019;104:659–68.

    Article  CAS  Google Scholar 

  16. McLornan DP, Szydlo R, Robin M, van Biezen A, Koster L, Blok HJP, et al. Outcome of patients with Myelofibrosis relapsing after allogeneic stem cell transplant: a retrospective study by the Chronic Malignancies Working Party of EBMT. Br J Haematol. 2018;182:418–22.

    Article  Google Scholar 

  17. Klyuchnikov E, Holler E, Bornhäuser M, Kobbe G, Nagler A, Shimoni A, et al. Donor lymphocyte infusions and second transplantation as salvage treatment for relapsed myelofibrosis after reduced-intensity allografting. Br J Haematol. 2012;159:172–81.

    Article  Google Scholar 

  18. Janson D, Ayuk FA, Wolschke C, Christopeit M, Badbaran A, von Pein U-M, et al. Ruxolitinib for myelofibrosis patients relapsing after allogeneic hematopoietic transplantation. Blood. 2016;128:1948–1948.

    Article  Google Scholar 

  19. Nagler A, Labopin M, Dholaria B, Finke J, Brecht A, Schanz U, et al. Second allogeneic stem cell transplantation in patients with acute lymphoblastic leukaemia: a study on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation. Br J Haematol. 2019;186:767–76.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  21. McLornan D, Szydlo R, Koster L, Chalandon Y, Robin M, Wolschke C, et al. Myeloablative and reduced-intensity conditioned allogeneic hematopoietic stem cell transplantation in myelofibrosis: a retrospective study by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2019;25:2167–71.

    Article  Google Scholar 

  22. Christopeit M, Kuss O, Finke J, Bacher U, Beelen DW, Bornhäuser M, et al. Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change. JCO. 2013;31:3259–71.

    Article  Google Scholar 

  23. Shimoni A, Labopin M, Finke J, Ciceri F, Deconinck E, Kröger N, et al. Donor selection for a second allogeneic stem cell transplantation in AML patients relapsing after a first transplant: a study of the Acute Leukemia Working Party of EBMT. Blood Cancer J. 2019;9:88.

    Article  Google Scholar 

  24. Robin M, Tabrizi R, Mohty M, Furst S, Michallet M, Bay J-O, et al. Allogeneic haematopoietic stem cell transplantation for myelofibrosis: a report of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC): allogeneic HSCT for myelofibrosis. Br J Haematol. 2011;152:331–9.

    Article  Google Scholar 

  25. Robin M, Zine M, Chevret S, Meignin V, Munoz-Bongrand N, Moatti H, et al. The impact of splenectomy in myelofibrosis patients before allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2017;23:958–64.

    Article  Google Scholar 

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Acknowledgements

The authors would like to thank all investigators and data managers in the EBMT participating centres for their dedicated patient care and Junfeng Wang for his contribution to the statistical analysis.

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Authors and Affiliations

  1. Division of Hematology, Hôpitaux Universitaires De Genève and Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Mitja Nabergoj & Yves Chalandon

  2. EBMT Statistical Unit Date Office, Leiden, the Netherlands

    Katya Mauff

  3. Hôpital Saint-Louis, APHP, Université Paris 7, Paris, France

    Marie Robin

  4. University Hospital Eppendorf, Hamburg, Germany

    Nicolaus Kröger

  5. Ematologia e Centro Trapianti, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Emanuele Angelucci

  6. Cliniques Universitaires St. Luc, Brussels, Belgium

    Xavier Poiré

  7. University Hospital, Basel, Switzerland

    Jakob Passweg

  8. University of Heidelberg, Heidelberg, Germany

    Aleksandar Radujkovic

  9. Department of Hematology and Cellular Therapy, University Hospital of Leipzig, Leipzig, Germany

    Uwe Platzbecker

  10. Bristol Royal Hospital for Children, Bristol, UK

    Stephen Robinson

  11. University of Milan and Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy

    Alessandro Rambaldi

  12. Bone Marrow Transplant Unit, Copenhagen, Denmark

    Søren Lykke Petersen

  13. Universitaetsklinikum Dresden, Dresden, Germany

    Fridrich Stölzel

  14. University of Muenster, Muenster, Germany

    Matthias Stelljes

  15. Ospedale San Raffaele, Milano, Italy

    Fabio Ciceri

  16. University Hospital Brno, Brno, Czech Republic

    Jiri Mayer

  17. H SS. Antonio e Biagio, Alessandria, Italy

    Marco Ladetto

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

    Liesebeth C. de Wreede

  19. EBMT Data Office, Leiden, the Netherlands

    Linda Koster

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

    Patrick J. Hayden

  21. Maria Skłodowska-Curie Institute - Cancer Center, Gliwice Branch, Gliwice, Poland

    Tomasz Czerw

  22. Department of Hematology, Hospital Clínico Universitario, Valencia, Spain

    Juan Carlos Hernández-Boluda

  23. Department of Haematology, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK

    Donal McLornan

  24. CHU de Lille, univ Lille, INSERM U1286, INFINITE, 59000, Lille, France

    Ibrahim Yakoub-Agha

Authors
  1. Mitja Nabergoj
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  3. Marie Robin
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  13. Fridrich Stölzel
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  14. Matthias Stelljes
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  15. Fabio Ciceri
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  16. Jiri Mayer
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  17. Marco Ladetto
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  18. Liesebeth C. de Wreede
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  19. Linda Koster
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  20. Patrick J. Hayden
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  22. Juan Carlos Hernández-Boluda
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  23. Donal McLornan
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  24. Yves Chalandon
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  25. Ibrahim Yakoub-Agha
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Corresponding authors

Correspondence to Mitja Nabergoj or Ibrahim Yakoub-Agha.

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Nabergoj, M., Mauff, K., Robin, M. et al. Outcomes following second allogeneic haematopoietic cell transplantation in patients with myelofibrosis: a retrospective study of the Chronic Malignancies Working Party of EBMT. Bone Marrow Transplant 56, 1944–1952 (2021). https://doi.org/10.1038/s41409-021-01271-4

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  • DOI: https://doi.org/10.1038/s41409-021-01271-4

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