Niels Smedegaard Andersen1, Martin Bornhäuser2,3, Martin Gramatzki4, Peter Dreger5, Antonin Vitek6, Michal Karas7, Mauricette Michallet8, Carol Moreno9, Michel van Gelder10, Anja Henseler11, Liesbeth C de Wreede11, Stefan Schönland5, Nicolaus Kröger12, Johannes Schetelig13,14. 1. BMT Unit Department of Hematology, Rigshospitalet, Copenhagen, Denmark. 2. Medical Department I, University Hospital Dresden, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany. 3. DKMS gGmbH, Dresden, Germany. 4. Division of Stem Cell Transplantation and Immunotherapy, University Hospital Schleswig-Holstein, Kiel, Germany. 5. Medizinische Klinik u. Poliklinik V, University of Heidelberg, Heidelberg, Germany. 6. Department of Haematology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic. 7. Department of Hematology/Oncology, Charles University Hospital, Pilsen, Czech Republic. 8. Centre Hospitalier Lyon-Sud-Hématologie, Lyon, France. 9. Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 10. Department of Internal Medicine Hematology, University Hospital Maastricht, Maastricht, The Netherlands. 11. Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. 12. Bone Marrow Transplantation Centre, University Hospital Eppendorf, Hamburg, Germany. 13. Medical Department I, University Hospital Dresden, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany. Johannes.schetelig@uniklinikum-dresden.de. 14. DKMS gGmbH, Dresden, Germany. Johannes.schetelig@uniklinikum-dresden.de.
Abstract
PURPOSE: The optimal dose intensity for conditioning prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) for chronic lymphocytic leukemia (CLL) is unknown. METHODS: We retrospectively compared outcomes of patients who received a first alloHCST after non-myeloablative (NMA) and reduced intensity conditioning (RIC). Data of 432 patients with a median age of 55 years were included, of which 86 patients underwent NMA and 346 RIC. RESULTS: The median follow-up after alloHSCT was 4.3 years. Compared to the RIC group, more NMA patients had purine-analog-sensitive disease, were in complete remission and received matched related donor transplantation. After RIC, the probabilities for 5-year OS, EFS, CIR, and NRM were 46%, 38%, 28%, and 35% and after NMA the respective probabilities were 52%, 43%, 25%, and 32%. In multivariate analysis, remission status prior to conditioning but not RIC versus NMA conditioning had a significant impact on CIR, EFS, and OS. CONCLUSION: Presumed higher anti-leukemic activity of RIC versus NMA conditioning did not translate into better outcomes after alloHSCT, but better remission status prior to conditioning did. Effective pathway inhibitor-based salvage therapies combined with NMA conditioning might thus represent the most attractive contemporary approach for alloHSCT for patients with CLL.
PURPOSE: The optimal dose intensity for conditioning prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) for chronic lymphocytic leukemia (CLL) is unknown. METHODS: We retrospectively compared outcomes of patients who received a first alloHCST after non-myeloablative (NMA) and reduced intensity conditioning (RIC). Data of 432 patients with a median age of 55 years were included, of which 86 patients underwent NMA and 346 RIC. RESULTS: The median follow-up after alloHSCT was 4.3 years. Compared to the RIC group, more NMApatients had purine-analog-sensitive disease, were in complete remission and received matched related donor transplantation. After RIC, the probabilities for 5-year OS, EFS, CIR, and NRM were 46%, 38%, 28%, and 35% and after NMA the respective probabilities were 52%, 43%, 25%, and 32%. In multivariate analysis, remission status prior to conditioning but not RIC versus NMA conditioning had a significant impact on CIR, EFS, and OS. CONCLUSION: Presumed higher anti-leukemic activity of RIC versus NMA conditioning did not translate into better outcomes after alloHSCT, but better remission status prior to conditioning did. Effective pathway inhibitor-based salvage therapies combined with NMA conditioning might thus represent the most attractive contemporary approach for alloHSCT for patients with CLL.
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