Peter Bader1, Hermann Kreyenberg2, Arend von Stackelberg2, Cornelia Eckert2, Emilia Salzmann-Manrique2, Roland Meisel2, Ulrike Poetschger2, Daniel Stachel2, Martin Schrappe2, Julia Alten2, Andre Schrauder2, Ansgar Schulz2, Peter Lang2, Ingo Müller2, Michael H Albert2, Andre M Willasch2, Thomas E Klingebiel2, Christina Peters2. 1. Peter Bader, Hermann Kreyenberg, Emilia Salzmann-Manrique, Andre M. Willasch, and Thomas E. Klingebiel, University Hospital for Children and Adolescents, Frankfurt/Main; Arend von Stackelberg and Cornelia Eckert, Children's Hospital Charité, Berlin, Berlin; Roland Meisel, Heinrich-Heine-University, Düsseldorf; Daniel Stachel, University Hospital Erlangen, Erlangen; Martin Schrappe, Julia Alten, Andre Schrauder, Christian-Albrechts-University and Medical Center Schleswig-Holstein, Kiel; Ansgar Schulz, University Medical Center, Ulm; Peter Lang, University Children's Hospital, Tuebingen; Ingo Müller, University Medical Center Hamburg-Eppendorf, Hamburg; Michael H. Albert, University Children's Hospital, Munich, Germany; and Ulrike Poetschger and Christina Peters, St Anna Children's Hospital, Vienna, Austria. peter.bader@kgu.de. 2. Peter Bader, Hermann Kreyenberg, Emilia Salzmann-Manrique, Andre M. Willasch, and Thomas E. Klingebiel, University Hospital for Children and Adolescents, Frankfurt/Main; Arend von Stackelberg and Cornelia Eckert, Children's Hospital Charité, Berlin, Berlin; Roland Meisel, Heinrich-Heine-University, Düsseldorf; Daniel Stachel, University Hospital Erlangen, Erlangen; Martin Schrappe, Julia Alten, Andre Schrauder, Christian-Albrechts-University and Medical Center Schleswig-Holstein, Kiel; Ansgar Schulz, University Medical Center, Ulm; Peter Lang, University Children's Hospital, Tuebingen; Ingo Müller, University Medical Center Hamburg-Eppendorf, Hamburg; Michael H. Albert, University Children's Hospital, Munich, Germany; and Ulrike Poetschger and Christina Peters, St Anna Children's Hospital, Vienna, Austria.
Abstract
PURPOSE: To elucidate the impact of minimal residual disease (MRD) after allogeneic transplantation, the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster Stem Cell Transplantation Group (ALL-BFM-SCT) conducted a prospective clinical trial. PATIENTS AND METHODS: In the ALL-BFM-SCT 2003 trial, MRD was assessed in the bone marrow at days +30, +60, +90, +180, and +365 after transplantation in 113 patients with relapsed disease. Standardized quantification of MRD was performed according to the guidelines of the Euro-MRD Group. RESULTS: All patients showed a 3-year probability of event-free survival (pEFS) of 55%. The cumulative incidence rates of relapse and treatment-related mortality were 32% and 12%, respectively. The pEFS was 60% for patients who received their transplantations in second complete remission, 50% for patients in ≥ third complete remission, and 0% for patients not in remission (P = .015). At all time points, the level of MRD was inversely correlated with event-free survival (EFS; P < .004) and positively correlated with the cumulative incidence of relapse (P < .01). A multivariable Cox model was fitted for each time point, which showed that MRD ≥ 10(-4) leukemic cells was consistently correlated with inferior EFS (P < .003). The accuracy of MRD measurements in predicting relapse was investigated with time-dependent receiver operating curves at days +30, +60, +90, and +180. From day +60 onward, the discriminatory power of MRD detection to predict the probability of relapse after 1, 3, 6, and 9 months was more than 96%, more than 87%, more than 71%, and more than 61%, respectively. CONCLUSION: MRD after transplantation was a reliable marker for predicting impending relapses and could thus serve as the basis for pre-emptive therapy.
PURPOSE: To elucidate the impact of minimal residual disease (MRD) after allogeneic transplantation, the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster Stem Cell Transplantation Group (ALL-BFM-SCT) conducted a prospective clinical trial. PATIENTS AND METHODS: In the ALL-BFM-SCT 2003 trial, MRD was assessed in the bone marrow at days +30, +60, +90, +180, and +365 after transplantation in 113 patients with relapsed disease. Standardized quantification of MRD was performed according to the guidelines of the Euro-MRD Group. RESULTS: All patients showed a 3-year probability of event-free survival (pEFS) of 55%. The cumulative incidence rates of relapse and treatment-related mortality were 32% and 12%, respectively. The pEFS was 60% for patients who received their transplantations in second complete remission, 50% for patients in ≥ third complete remission, and 0% for patients not in remission (P = .015). At all time points, the level of MRD was inversely correlated with event-free survival (EFS; P < .004) and positively correlated with the cumulative incidence of relapse (P < .01). A multivariable Cox model was fitted for each time point, which showed that MRD ≥ 10(-4) leukemic cells was consistently correlated with inferior EFS (P < .003). The accuracy of MRD measurements in predicting relapse was investigated with time-dependent receiver operating curves at days +30, +60, +90, and +180. From day +60 onward, the discriminatory power of MRD detection to predict the probability of relapse after 1, 3, 6, and 9 months was more than 96%, more than 87%, more than 71%, and more than 61%, respectively. CONCLUSION: MRD after transplantation was a reliable marker for predicting impending relapses and could thus serve as the basis for pre-emptive therapy.
Authors: Klaus Wethmar; Svenja Matern; Eva Eßeling; Linus Angenendt; Heike Pfeifer; Monika Brüggemann; Patrick Stelmach; Simon Call; Jörn C Albring; Jan-Henrik Mikesch; Christian Reicherts; Christoph Groth; Christoph Schliemann; Wolfgang E Berdel; Georg Lenz; Matthias Stelljes Journal: Bone Marrow Transplant Date: 2020-01-30 Impact factor: 5.483
Authors: Eva Rettinger; Sabine Huenecke; Halvard Bonig; Michael Merker; Andrea Jarisch; Jan Soerensen; Andre Willasch; Gesine Bug; Ansgar Schulz; Thomas Klingebiel; Peter Bader Journal: Haematologica Date: 2016-01-14 Impact factor: 9.941
Authors: M Kotrova; V H J van der Velden; J J M van Dongen; R Formankova; P Sedlacek; M Brüggemann; J Zuna; J Stary; J Trka; E Fronkova Journal: Bone Marrow Transplant Date: 2017-02-27 Impact factor: 5.483