C Craddock1, J Versluis2, M Labopin3, G Socie4, A Huynh5, E Deconinck6, L Volin7, N Milpied8, J H Bourhis9, A Rambaldi10, P Chevallier8, D Blaise11, M Manz12, E Vellenga13, M-C Vekemans14, J Maertens15, J Passweg16, P Vyas17, C Schmid18, B Löwenberg2, G Ossenkoppele19, M Mohty20, J J Cornelissen2, A Nagler21,22. 1. Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK. 2. Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands. 3. Department of Haematology, Hospital Saint Antoine, Paris, France. 4. Department of Hematology, Hospital Saint-Louis, Sorbonne University, Paris, France. 5. Department of Haematology, CHU, Toulouse, France. 6. Department of Hematology, CHU, Besancon, France. 7. Stem Cell Transplantation Unit, HUCH Comprehensive Cancer Center, Helsinki, Finland. 8. Department of Hamatology, CHU, Nantes, France. 9. Department of Medical Oncology, Institute of Cancer, Villejuif, France. 10. Department of Hematology, University of Milan, Milan, Italy. 11. Department of Hematology, Centre of Cancer Research, Marseille, France. 12. Center for Hemato-Oncology, University Hospital Zurich, Zurich, Switzerland. 13. Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands. 14. Department of Hematology, Saint-Luc University, Brussels, Belgium. 15. Department of Haematology, University Hospital Gasthuisberg, Leuven, Belgium. 16. Department of Haematology, University of Basel, Basel, Switzerland. 17. Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. 18. Stem Cell Transplantation Unit, Department of Medicine, University of Munich, Munich, Germany. 19. Department of Haematology, University Medical Center, Amsterdam, The Netherlands. 20. Hospital Saint-Antoine, University UPMC, Paris, France. 21. Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. 22. ALWP office of the EBMT Hospital Saint Antoine, Paris, France.
Abstract
BACKGROUND: Disease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT). AIMS: The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized. MATERIALS AND METHODS: We have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo-SCT for AML in CR1 and separately 570 patients treated with IC alone. RESULTS: In the first 3 months after allo-SCT, the factors associated with an increased risk of relapse included the presence of the FLT3-ITD (P < 0.001), patient age (P = 0.012), time interval from CR1 to transplant (P < 0.001) and donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher white cell count at diagnosis (P = 0.001), adverse-risk cytogenetics (P < 0.001), presence of FLT3-ITD mutation (P < 0.001) and time interval to achieve first complete remission (P = 0.013). Later relapse was associated with adverse cytogenetics, mutated NPM1, absence of chronic graft-versus-host disease (GVHD) and the use of in vivo T-cell depletion. In patients treated with IC alone, the factors associated with relapse in the first 3 months were adverse-risk cytogenetics (P < 0.001) and FLT3-ITD status (P = 0.001). The factors predicting later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time interval from CR1 to IC (P = 0.012). DISCUSSION AND CONCLUSION: Taken together, these data provide novel insights into the biology of disease recurrence after both allo-SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical settings.
BACKGROUND: Disease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT). AIMS: The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized. MATERIALS AND METHODS: We have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo-SCT for AML in CR1 and separately 570 patients treated with IC alone. RESULTS: In the first 3 months after allo-SCT, the factors associated with an increased risk of relapse included the presence of the FLT3-ITD (P < 0.001), patient age (P = 0.012), time interval from CR1 to transplant (P < 0.001) and donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher white cell count at diagnosis (P = 0.001), adverse-risk cytogenetics (P < 0.001), presence of FLT3-ITD mutation (P < 0.001) and time interval to achieve first complete remission (P = 0.013). Later relapse was associated with adverse cytogenetics, mutated NPM1, absence of chronic graft-versus-host disease (GVHD) and the use of in vivo T-cell depletion. In patients treated with IC alone, the factors associated with relapse in the first 3 months were adverse-risk cytogenetics (P < 0.001) and FLT3-ITD status (P = 0.001). The factors predicting later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time interval from CR1 to IC (P = 0.012). DISCUSSION AND CONCLUSION: Taken together, these data provide novel insights into the biology of disease recurrence after both allo-SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical settings.
Authors: Mark-Alexander Schwarzbich; Hao Dai; Lambros Kordelas; Dietrich W Beelen; Aleksandar Radujkovic; Carsten Müller-Tidow; Peter Dreger; Thomas Luft Journal: Int J Mol Sci Date: 2022-02-20 Impact factor: 5.923
Authors: Esther Schuler; Eva-Maria Wagner-Drouet; Salem Ajib; Gesine Bug; Martina Crysandt; Sabine Dressler; Andreas Hausmann; Daniela Heidenreich; Klaus Hirschbühl; Matthias Hoepting; Edgar Jost; Jennifer Kaivers; Stefan Klein; Michael Koldehoff; Lambros Kordelas; Oliver Kriege; Lutz P Müller; Christina Rautenberg; Judith Schaffrath; Christoph Schmid; Daniel Wolff; Rainer Haas; Martin Bornhäuser; Thomas Schroeder; Guido Kobbe Journal: Ann Hematol Date: 2020-11-16 Impact factor: 3.673