Nicolaus Kröger1, Katja Sockel2, Christine Wolschke1, Wolfgang Bethge3, Richard F Schlenk4,5, Dominik Wolf6,7,8, Michael Stadler9, Guido Kobbe10, Gerald Wulf11, Gesine Bug12, Kerstin Schäfer-Eckart13, Christof Scheid14, Florian Nolte15, Jan Krönke16, Matthias Stelljes17, Dietrich Beelen18, Marion Heinzelmann1, Detlef Haase11, Hannes Buchner19, Gabriele Bleckert19, Aristoteles Giagounidis20, Uwe Platzbecker2,21. 1. University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 2. Medical Clinic and Policlinic 1, University Hospital "Carl Gustav Carus" Dresden, Dresden, Germany. 3. University Hospital Tübingen, Tübingen, Germany. 4. Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany. 5. NCT-Trial Center, National Center of Tumor Diseases Heidelberg, German Cancer Research Center, Heidelberg, Germany. 6. Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria. 7. Tyrolean Cancer Research Institute, Innsbruck, Austria. 8. Medical Clinic III, University Clinic Bonn, Bonn, Germany. 9. Hannover Medical School, Hannover, Germany. 10. University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany. 11. University Medical Center Göttingen, Göttingen, Germany. 12. Department of Medicine 2, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany. 13. Department of Medicine 5, Paracelsus Private University Nuremberg, Nuremberg, Germany. 14. Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn, University of Cologne, Cologne Düsseldorf, Germany. 15. Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany. 16. University Hospital Ulm, Ulm, Germany. 17. University Medical Center Münster, Münster, Germany. 18. University Medical Center Essen, Essen, Germany. 19. Staburo München, Statistical Consulting, Munich, Germany. 20. St Mary's Hospital, Düsseldorf, Germany. 21. University of Leipzig Medical Center, Leipzig, Germany.
Abstract
PURPOSE: In contrast to 5-azacytidine (5-aza), allogeneic stem-cell transplantation (HSCT) represents a curative treatment strategy for patients with myelodysplastic syndromes (MDS), but therapy-related mortality (TRM) limits its broader use in elderly patients with MDS. The present prospective multicenter study compared HSCT following 5-aza pretreatment with continuous 5-aza treatment in patients with higher-risk MDS age 55-70 years. METHODS: One hundred ninety patients with a median age of 63 years were enrolled. Patients received 4-6 cycles of 5-aza followed by HLA-compatible HSCT after reduced-intensity conditioning or by continuous 5-aza if no donor was identified. RESULTS: Twenty-eight patients did not fulfill inclusion criteria (n = 20), died (n = 2) withdrew informed consent (n = 5), or were excluded for an unknown reason (n = 1). 5-aza induction started in 162 patients, but only 108 (67%) were eligible for subsequent allocation to HSCT (n = 81) or continuation of 5-aza (n = 27) because of disease progression (n = 26), death (n = 12), or other reasons (n = 16). Seven percent died during 5-aza before treatment allocation. The cumulative incidence of TRM after HSCT at 1 year was 19%. The event-free survival and overall survival after 5-aza pretreatment and treatment allocation at 3 years were 34% (95% CI, 22 to 47) and 50% (95% CI, 39 to 61) after allograft and 0% and 32% (95% CI, 14 to 52) after continuous 5-aza treatment (P < .0001 and P = .12), respectively. Fourteen patients progressing after continuous 5-aza received a salvage allograft from an alternative donor, and 43% were alive at last follow-up. CONCLUSION: In older patients with MDS, reduced-intensity conditioning HSCT resulted in a significantly improved event-free survival in comparison with continuous 5-aza therapy. Bridging with 5-aza to HSCT before is associated with a considerable rate of dropouts because of progression, mortality, and adverse events.
PURPOSE: In contrast to 5-azacytidine (5-aza), allogeneic stem-cell transplantation (HSCT) represents a curative treatment strategy for patients with myelodysplastic syndromes (MDS), but therapy-related mortality (TRM) limits its broader use in elderly patients with MDS. The present prospective multicenter study compared HSCT following 5-aza pretreatment with continuous 5-aza treatment in patients with higher-risk MDS age 55-70 years. METHODS: One hundred ninety patients with a median age of 63 years were enrolled. Patients received 4-6 cycles of 5-aza followed by HLA-compatible HSCT after reduced-intensity conditioning or by continuous 5-aza if no donor was identified. RESULTS: Twenty-eight patients did not fulfill inclusion criteria (n = 20), died (n = 2) withdrew informed consent (n = 5), or were excluded for an unknown reason (n = 1). 5-aza induction started in 162 patients, but only 108 (67%) were eligible for subsequent allocation to HSCT (n = 81) or continuation of 5-aza (n = 27) because of disease progression (n = 26), death (n = 12), or other reasons (n = 16). Seven percent died during 5-aza before treatment allocation. The cumulative incidence of TRM after HSCT at 1 year was 19%. The event-free survival and overall survival after 5-aza pretreatment and treatment allocation at 3 years were 34% (95% CI, 22 to 47) and 50% (95% CI, 39 to 61) after allograft and 0% and 32% (95% CI, 14 to 52) after continuous 5-aza treatment (P < .0001 and P = .12), respectively. Fourteen patients progressing after continuous 5-aza received a salvage allograft from an alternative donor, and 43% were alive at last follow-up. CONCLUSION: In older patients with MDS, reduced-intensity conditioning HSCT resulted in a significantly improved event-free survival in comparison with continuous 5-aza therapy. Bridging with 5-aza to HSCT before is associated with a considerable rate of dropouts because of progression, mortality, and adverse events.
Authors: C Lindholm; E Olofsson; M Creignou; L Nilsson; H Gravdahl Garelius; J Cammenga; P Ljungman; E Ejerblad; M Tobiasson Journal: Bone Marrow Transplant Date: 2022-02-02 Impact factor: 5.483