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.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Is the use of unrelated donor transplantation leveling off in Europe? The 2016 European Society for Blood and Marrow Transplant activity survey report
Bone Marrow Transplantation Open Access 14 March 2018
-
Who Is the Patient at Risk of CMV Recurrence: A Review of the Current Scientific Evidence with a Focus on Hematopoietic Cell Transplantation
Infectious Diseases and Therapy Open Access 04 December 2017
-
Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report
Bone Marrow Transplantation Open Access 13 March 2017
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Sureda A, Bader P, Cesaro S, Dreger P, Duarte RF, Dufour C et al. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe Bone Marrow Transplant 2015; 50: 1037–1056.
Copelan EA . Hematopoietic stem-cell transplantation. N Engl J Med 2006; 354: 1813–1826.
Gratwohl A, Pasquini MC, Aljurf M, Atsuta Y, Baldomero H, Foeken L et al. Worldwide Network for Blood and Marrow Transplantation (WBMT). One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematol 2015; 2: e91–e100.
Pasquini MC, Wang Z, Horowitz MM, Gale RP . 2010 report from the Center for International Blood and Marrow Transplant Research (CIBMTR): current uses and outcomes of hematopoietic cell transplants for blood and bone marrow disorders. Clin Transpl 2010; 2010: 87–105.
Passweg JR, Baldomero H, Bader P, Bonini C, Cesaro S, Dreger P et al. Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually. Bone Marrow Transplant 2016; 51: 786–792.
Passweg JR, Baldomero H, Gratwohl A, Bregni M, Cesaro S, Dreger P et al. European Group for Blood and Marrow Transplantation (EBMT). The EBMT activity survey: 1990-2010. Bone Marrow Transplant 2012; 47: 906–923.
Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med 2010; 363: 2091–2101.
Cheson BD, Lacerna L, Leyland-Jones B, Sarosy G, Wittes RE . Autologous bone marrow transplantation. Current status and future directions. Ann Intern Med 1989; 110: 51–65.
Schulman KA, Stadtmauer EA, Reed SD, Glick HA, Goldstein LJ, Pines JM et al. Economic analysis of conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. Bone Marrow Transplant 2003; 31: 205–210.
Vogl DT, Stadtmauer EA . High-dose chemotherapy and autologous hematopoietic stem cell transplantation for metastatic breast cancer: a therapy whose time has passed. Bone Marrow Transplant 2006; 37: 985–987.
Gratwohl A, Schwendener A, Baldomero H, Gratwohl M, Apperley J, Niederwieser D et al. Changes in the use of hematopoietic stem cell transplantation: a model for diffusion of medical technology. Haematologica 2010; 95: 637–643.
Sasaki K, Strom SS, O'Brien S, Jabbour E, Ravandi F, Konopleva M et al. Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials. Lancet Haematol 2015; 2: e186–e193.
Innes AJ, Apperley JF . Chronic myeloid leukemia-transplantation in the tyrosine kinase era. Hematol Oncol Clin North Am 2014; 28: 1037–1053.
Mitchell JM, Conklin EA . Factors affecting receipt of expensive cancer treatments and mortality: evidence from stem cell transplantation for leukemia and lymphoma. Health Serv Res 2015; 50: 197–216.
Gratwohl A . Bone marrow transplantation activity in Europe 1990. European Group for Bone Marrow Transplantation (EBMT). Bone Marrow Transplant 1991; 8: 197–201.
Gratwohl A, Baldomero H, Frauendorfer K, Urbano-Ispizua A . EBMT activity survey 2004 and changes in disease indication over the past 15 years. Bone Marrow Transplant 2006; 37: 1069–1085.
Gratwohl A, Baldomero H, Horisberger B, Schmid C, Passweg J, Urbano-Ispizua A . Current trends in hematopoietic stem cell transplantation in Europe. Blood 2002; 100: 2374–2386.
Gratwohl A, Baldomero H, Rosti G . High-dose chemotherapy for breast cancer. Bone Marrow Transplant 2000; 26: 599.
Gratwohl A, Baldomero H, Schwendener A, Gratwohl M, Apperley J, Niederwieser D et al. Predictability of hematopoietic stem cell transplantation rates. Haematologica 2007; 92: 1679–1686.
Gratwohl A, Baldomero H, Passweg J . The role of hematopoietic stem cell transplantation in chronic myeloid leukemia. Ann Hematol 2015; 94: S177–S186.
European Leukemia Net guidelines. Available at http://www.leukemia-net.org/content/physicians/recommendations/index_eng.html.
Michallet M, Dreger P, Sutton L, Brand R, Richards S, van Os M et al. Autologous hematopoietic stem cell transplantation in chronic lymphocytic leukemia: results of European intergroup randomized trial comparing autografting versus observation. Blood 2011; 117: 1516–1521.
Dreger P, Döhner H, McClanahan F, Busch R, Ritgen M, Greinix H et al. Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial. Blood 2012; 119: 4851–4859.
Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 2012; 367: 11–19.
Peters WP, Shpall EJ, Jones RB, Olsen GA, Bast RC, Gockerman JP et al. High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer. J Clin Oncol 1988; 6: 1368–1376.
Berry DA, Ueno NT, Johnson MM, Lei X, Caputo J, Rodenhuis S et al. High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: overview of 15 randomized trials. J Clin Oncol 2011; 29: 3214–3223.
Pedrazzoli P, Martino M, Delfanti S, Generali D, Rosti G, Bregni M et al. High-dose chemotherapy with autologous hematopoietic stem cell transplantation for high-risk primary breast cancer. J Natl Cancer Inst Monogr 2015; 51: 70–75.
Bezwoda WR, Seymour L, Dansey RD . High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial. J Clin Oncol 1995; 13: 2483–2489.
Ruiz-Argüelles GJ, Tarin-Arzaga LC, Gonzalez-Carrillo ML, Gutierrez-Riveroll KI, Rangel-Malo R, Gutiérrez-Aguirre CH et al. Therapeutic choices in patients with Ph-positive CML living in Mexico in the tyrosine kinase inhibitor era: SCT or TKIs? Bone Marrow Transplant 2008; 42: 23–28.
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.
Author information
Authors and Affiliations
Consortia
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2016.258
This article is cited by
-
The association of graft-versus-leukemia effect and graft-versus host disease in haploidentical transplantation with post-transplant cyclophosphamide for AML
Bone Marrow Transplantation (2022)
-
Determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation
Leukemia (2021)
-
Allogeneic stem cell transplantation for chronic myeloid leukemia in the TKI era: population-based data from the Swedish CML registry
Bone Marrow Transplantation (2019)
-
Is the use of unrelated donor transplantation leveling off in Europe? The 2016 European Society for Blood and Marrow Transplant activity survey report
Bone Marrow Transplantation (2018)
-
Who Is the Patient at Risk of CMV Recurrence: A Review of the Current Scientific Evidence with a Focus on Hematopoietic Cell Transplantation
Infectious Diseases and Therapy (2018)