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Splenic irradiation before hematopoietic stem cell transplantation for chronic myeloid leukemia: long-term follow-up of a prospective randomized study

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Abstract

In the context of discussions on the reproducibility of clinical studies, we reanalyzed a prospective randomized study on the role of splenic irradiation as adjunct to the conditioning for hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML). Between 1986 and 1989, a total of 229 patients with CML were randomized; of these, 225 (98 %; 112 with, 113 without splenic irradiation) could be identified in the database and their survival updated. Results confirmed the early findings with no significant differences in all measured endpoints (overall survival at 25 years: 42.7 %, 32.0–52.4 % vs 52.9 %, 43.2–62.6 %; p = 0.355, log rank test). Additional splenic irradiation failed to reduce relapse incidence. It did not increase non-relapse mortality nor the risk of late secondary malignancies. Comforting are the long-term results from this predefined consecutive cohort of patients: more than 60 % were alive at plus 25 years when they were transplanted with a low European Society for Blood and Marrow Transplantation (EBMT) risk sore. This needs to be considered today when treatment options are discussed for patients who failed initial tyrosine kinase inhibitor therapy and have an available low risk HLA-identical donor.

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Acknowledgments

The authors would like to thank all participating patients and transplant teams.

Author information

Author notes

  1. Francesco Frassoni

    Present address: Ospedale Gaslini, Genova, Italy

  2. Hartmut Link

    Present address: Westpfalzklinikum, Kaiserslautern, Germany

  3. Dietger Niederwieser

    Present address: Hematology-Oncology, University Hospital, Leipzig, Germany

Authors and Affiliations

  1. The European Society for Blood and Marrow Transplantation (EBMT) Activity Survey Office, University Hospital, Basel, CH-4031, Basel, Switzerland

    Alois Gratwohl & Helen Baldomero

  2. Centro Interdipartimentale di Biostatistica e Bioinformatica, Università di Roma Tor Vergata, Rome, Italy

    Simona Iacobelli

  3. EBMT Data Office Leiden, Leiden, The Netherlands

    Natalia Bootsman & Anja van Biezen

  4. Rome Transplant Network, ¨Tor Vergata¨ University of Rome, Stem Cell Transplant Unit, Policlinico Universitario Tor Vergata, Rome, Italy

    William Arcese

  5. Hematology-Oncology, Charité Universitätsmedizin, Campus Virchow Klinikum, Berlin, Germany

    Renate Arnold

  6. Experimental Hematology, Institut Jules Bordet, Brussels, Belgium

    Dominique Bron

  7. Hematology, Hôpital Mondor, Créteil, France

    Catherine Cordonnier

  8. King Faisal Specialist Hospital & Research Centre, Oncology, Section of Adult Haematolgy/BMT, Riyadh, Saudi Arabia

    Peter Ernst

  9. Department of Haematology, Cliniques Universitaires St. Luc, Brussels, Belgium

    Augustin Ferrant

  10. Department of Haematology II, Ospedale San Martino, Genova, Italy

    Francesco Frassoni

  11. Department of Hematology, Karolinska University Hospital, Stockholm, Sweden

    Gösta Gahrton

  12. Hospital U. Marqués de Valdecilla, Servicio de Hematología-Hemoterapia, c/ Marqués de Valdecilla, Santander, Spain

    Carlos Richard

  13. Klinikum Grosshadern, Med. Klinik III, Munich, Germany

    Hans Jochem Kolb

  14. Medizinische Hochschule Hannover, Hannover, Germany

    Hartmut Link

  15. Universitätsklinikum, Hämatologie, Innsbruck, Austria

    Dietger Niederwieser

  16. University of Helsinki Hospital, Helsinki, Finland

    Tapani Ruutu

  17. Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands

    Anton Schattenberg

  18. Department of Hematology, Asklepios Klinik St. Georg, Hamburg, Germany

    Norbert Schmitz

  19. Hematology, Hospital Reina Sofia, Córdoba, Spain

    Antonio Torres-Gomez

  20. Leiden University Medical Center, Leiden, The Netherlands

    Ferry Zwaan

  21. Department of Haematology, Imperial College, Hammersmith Hospital, London, UK

    Jane Apperley

  22. Department of Haematology, Complejo Hospitalario de Navarra, Pamplona, Spain

    Eduardo Olavarria

  23. Hematology, University Hospital Hamburg, Hamburg, Germany

    Nicolaus Kröger

Authors
  1. Alois Gratwohl
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  2. Simona Iacobelli
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  3. Natalia Bootsman
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  4. Anja van Biezen
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  5. Helen Baldomero
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  6. William Arcese
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  7. Renate Arnold
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  8. Dominique Bron
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  9. Catherine Cordonnier
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  10. Peter Ernst
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  11. Augustin Ferrant
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  12. Francesco Frassoni
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  13. Gösta Gahrton
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  14. Carlos Richard
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  15. Hans Jochem Kolb
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  16. Dietger Niederwieser
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  17. Tapani Ruutu
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  18. Anton Schattenberg
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  19. Norbert Schmitz
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  20. Antonio Torres-Gomez
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  21. Ferry Zwaan
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  22. Jane Apperley
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  23. Eduardo Olavarria
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  24. Nicolaus Kröger
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Consortia

for the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation EBMT

Corresponding author

Correspondence to Helen Baldomero.

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Conflicts of interest

There are no conflicts of interest to declare.

Funding

The study was funded by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation EBMT. EBMT is supported by grants from the corporate members: Amgen Europe, ViroPharma Europe, Celegene International SARL, Genzyme Europe B.V., Gilead Sciences Europe Ltd., MiltenylBiotec GmbH, Schering-Plough International Inc., Bristol Myers Squibb, CaridiaBCT Europe NV, Cephalon Europe, F. Hoffmann-La Roche Ltd, Fresenius Biotech GmbH, Therakos Inc., Alexion Europe, Chugai Sanofi – Aventis, Merck Sharp and Dohme, Novartis, Pfizer, Pierre Fabre Médicament.

Appendix

Appendix

List of participating centers with past (ref Gratwohl et al. 1996) and current principal investigators.

Basel: Kantonsspital (today University Hospital; B. Speck, A. Gratwohl, J. Passweg); Berlin: University Hospital Rudolf Virchow (W. Siegert, R. Arnold); Birmingham: Queen Elizabeth Hospital (I.M. Franklin, C. Craddock); Brussels: Insitut J. Bordet (L. Debusscher, D. Bron), Hôpital Universitaire St. Luc (A. Ferrant, X. Poiré); Caen: Centre Hospitalier (X.Troussard, O. Reman); Copenhagen: University Hospital (N. Jacobsen, H. Sengeloev); Córdoba: Hospital Reina Sofia (A. Torrez-Gomez, P. Gomez Garcia); Créteil: HôpitalMondor (J.-P. Vernant, C. Cordonnier); Dublin: St. James’ Hospital (S.R. McCann, P. Browne); Edinburgh: Royal Infirmary (A.C. Parker, A.J.M. Broom); Genova: Ospedale San Martino (A. Bacigalupo, F. Frassoni, A. Bacigalupo); Hannover: Medizinische Hochschule (H. Link, A. Ganser); Helsinki: University of Helsinki Hospital (T. Ruutu, L. Volin); Huddinge: Karolinska Institute (B. Lönnqvist, G. Gahrton, O. Ringden, P. Ljungman); Innsbruck: University Hospital (D. Niederwieser, G. Gastl); Kiel: Christian Albrechts University Hospital (N. Schmitz, M. Gramatzki); Leiden: University Hospital (F. Zwaan, W. Fibbe, J.H. Veelken); Lisbon: Ins. Portuges Oncologia (M. Abecasis, M. Abecasis); London: Harley Street clinic (P.J. Gravett), Royal Marsden Hospital (R. Powles, G. Helenglass, M. Potter), Royal Free Hospital (H.G. Prentice, S. McKinnon); Munich: Ludwig Maximilian University Hospital (H.J. Kolb, W.Hiddemann, J. Tischer); Nijmegen: Sint Radboud Ziekenhuis (T. deWitte, T. Schattenberg, N. Schaap); Paris: Centre Hospitalier St. Antoine (N.C. Gorin, L.Fouillard, M. Mohty); Pessac: Centre Hospitalier (J. Reiffers, N. Millpied); Riyadh: King Faisal Hospital (P. Ernst, M. Aljurf); Rome: UniversitadegliStudi di Roma La Sapienza (W. Arcese, P. de Fabritiis, R. Foa); Santander: Hospital Nacional “Marques de Valdecilla” (A. Iriondo, C. Richard Espiga); Vienna: Allgemeines Krankenhaus der Stadt Wien (W. Hinterberger, P. Kahls)

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Gratwohl, A., Iacobelli, S., Bootsman, N. et al. Splenic irradiation before hematopoietic stem cell transplantation for chronic myeloid leukemia: long-term follow-up of a prospective randomized study. Ann Hematol 95, 967–972 (2016). https://doi.org/10.1007/s00277-016-2638-6

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  • DOI: https://doi.org/10.1007/s00277-016-2638-6

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