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Impact of drug development on the use of stem cell transplantation: a report by the European Society for Blood and Marrow Transplantation (EBMT)

Abstract

Hematopoietic stem cell transplantation (HSCT) is used with increasing frequency in Europe with 40 000 transplants reported in 2014. Transplant-related mortality remains high in allogeneic HSCT (10–20%); high-dose chemotherapy is toxic and demanding for patients. Drug development is accelerating and with limited toxicity of some targeted drugs may replace HSCT, whereas others may function as a ‘bridge to transplant’. We analyzed HSCT reported to the activity survey for selected diseases in which major advances in drug development have been made. Tyrosine kinase inhibitors markedly changed the number of allogeneic HSCT in early CML. In myelodysplastic syndromes, hypomethylating agents show no effect on HSCT activity and Janus kinase inhibitors for myeloproliferative neoplasm appear to have only a temporary effect. For CLL autologous HSCT decreased after publication of trials showing improved PFS but no overall survival advantage and allogeneic rates are dropping after the introduction of Bruton kinase and PI3K Inhibitors. Whether these are ‘game changers’ as was imatinib for CML requires additional follow-up. For myeloma, proteasome inhibitors and new immunomodulatory drugs do not appear to impact transplant rates. Drug development data show different effects on HSCT use; highly effective drugs may replace HSCT, whereas other drugs may improve the patient’s condition to allow for HSCT.

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Acknowledgements

All teams participating in the EBMT annual survey on transplant activity and their staff, the EBMT Co-ordination offices; Barcelona, Paris, London (C Ruiz de Elvira), the Austrian Registry (ASCTR) (H Greinix, B Lindner, C Wagner), the Belgium Registry (Yves Beguin, M Van Spauwen) the Czech Registry (P Zak, M Trnkova, K Benesova), the French Registry (SFGM) (I Yakoub-Agha, N Raus ), the German Registry (DRST) (H Ottinger, K Fuchs, C Müller, H Neidlinger, F Hanke), the Italian Registry (GITMO) (F Bonifazi, B Bruno, E Oldani), the Dutch Registry (JJ Cornelissen, M Groenendijk), the Spanish Registry (GETH) (JL Diez-Martin, A Cedillo), the Swiss Registry (SBST) (U Schanz, H Baldomero), the Turkish Registry (G Gurman, M Arat) and the British Registry (BSBMT) (K Kirkland, J Perry) is greatly appreciated. The authors also thank D John for database support. EBMT is supported by grants from the corporate sponsors: Jazz Pharmaceuticals plc, Molmed SpA, Amgen Oncology GmbH, AstellasPharma Europe Ltd, Celgene International SARL, Clinigen Group Ltd, Gilead Sciences Europe Ltd., Hospira Inc., Janssen, Medac Hematology GmbH, MiltenyiBiotec GmbH, MSD Sharp & Dohme GmbH, Neovii Biotech GmbH, Pfizer Oncology, Sanofi Oncology, Takeda Pharmaceuticals, Therakos Photopheresis, Alexion, Apotex Advancing Generics, Basilea Pharmaceutica Ltd, Bellicum Pharmaceuticals, Cell Medica, Eurocept International, Kiadis Pharma, Macropharma, Mundipharma, Pierre Fabre Médicament and Terumo BCT. Writing of the manuscript was the sole responsibility of the authors.

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Passweg, J., Baldomero, H., Bader, P. et al. Impact of drug development on the use of stem cell transplantation: a report by the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 52, 191–196 (2017). https://doi.org/10.1038/bmt.2016.258

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