Christoph Röllig1, Martin Bornhäuser2, Michael Kramer2, Christian Thiede2, Anthony D Ho2, Alwin Krämer2, Kerstin Schäfer-Eckart2, Hannes Wandt2, Mathias Hänel2, Hermann Einsele2, Walter E Aulitzky2, Norbert Schmitz2, Wolfgang E Berdel2, Matthias Stelljes2, Carsten Müller-Tidow2, Utz Krug2, Uwe Platzbecker2, Martin Wermke2, Claudia D Baldus2, Stefan W Krause2, Friedrich Stölzel2, Malte von Bonin2, Markus Schaich2, Hubert Serve2, Johannes Schetelig2, Gerhard Ehninger2. 1. Christoph Röllig, Martin Bornhäuser, Michael Kramer, Christian Thiede, Uwe Platzbecker, Martin Wermke, Friedrich Stölzel, Malte von Bonin, Markus Schaich, Johannes Schetelig, and Gerhard Ehninger, Medizinische Klinik und Poliklinik I, Universitätsklinikum der Technischen Universität Dresden; Johannes Schetelig, DKMS, German Bone Marrow Donor Center, Dresden; Anthony D. Ho and Alwin Krämer, Medizinische Universitätsklinik, Abteilung Innere Medizin V, Heidelberg; Kerstin Schäfer-Eckart and Hannes Wandt, 5. Medizinische Klinik, Klinikum Nürnberg, Nürnberg; Mathias Hänel, Klinik für Innere Medizin III, Klinikum Chemnitz, Chemnitz; Hermann Einsele, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg; Walter E. Aulitzky, Robert-Bosch-Krankenhaus, Stuttgart; Norbert Schmitz, Abteilung für Hämatologie, Onkologie und Stammzelltransplantation, ASKLEPIOS Klinik St Georg, Hamburg; Wolfgang E. Berdel, Matthias Stelljes, and Utz Krug, Medizinische Klinik A, Universitätsklinikum Münster, Münster; Carsten Müller-Tidow, Universitätsklinik und Poliklinik für Innere Medizin IV, Universitätsklinikum Halle, Halle (Saale); Claudia D. Baldus, Medizinische Klinik III, Charité-Universitätsmedizin Berlin, Charité Centrum 14, Campus Benjamin Franklin, Berlin; Stefan W. Krause, Medizinische Klinik 5, Universitätsklinikum Erlangen, Erlangen; and Hubert Serve, Medizinische Klinik II, Universitätsklinikum Frankfurt, Frankfurt, Germany. christoph.roellig@uniklinikum-dresden.de. 2. Christoph Röllig, Martin Bornhäuser, Michael Kramer, Christian Thiede, Uwe Platzbecker, Martin Wermke, Friedrich Stölzel, Malte von Bonin, Markus Schaich, Johannes Schetelig, and Gerhard Ehninger, Medizinische Klinik und Poliklinik I, Universitätsklinikum der Technischen Universität Dresden; Johannes Schetelig, DKMS, German Bone Marrow Donor Center, Dresden; Anthony D. Ho and Alwin Krämer, Medizinische Universitätsklinik, Abteilung Innere Medizin V, Heidelberg; Kerstin Schäfer-Eckart and Hannes Wandt, 5. Medizinische Klinik, Klinikum Nürnberg, Nürnberg; Mathias Hänel, Klinik für Innere Medizin III, Klinikum Chemnitz, Chemnitz; Hermann Einsele, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg; Walter E. Aulitzky, Robert-Bosch-Krankenhaus, Stuttgart; Norbert Schmitz, Abteilung für Hämatologie, Onkologie und Stammzelltransplantation, ASKLEPIOS Klinik St Georg, Hamburg; Wolfgang E. Berdel, Matthias Stelljes, and Utz Krug, Medizinische Klinik A, Universitätsklinikum Münster, Münster; Carsten Müller-Tidow, Universitätsklinik und Poliklinik für Innere Medizin IV, Universitätsklinikum Halle, Halle (Saale); Claudia D. Baldus, Medizinische Klinik III, Charité-Universitätsmedizin Berlin, Charité Centrum 14, Campus Benjamin Franklin, Berlin; Stefan W. Krause, Medizinische Klinik 5, Universitätsklinikum Erlangen, Erlangen; and Hubert Serve, Medizinische Klinik II, Universitätsklinikum Frankfurt, Frankfurt, Germany.
Abstract
PURPOSE: The presence of a mutated nucleophosmin-1 gene (NPM1(mut)) in acute myeloid leukemia (AML) is associated with a favorable prognosis. To assess the predictive value with regard to allogeneic stem-cell transplantation (SCT), we compared the clinical course of patients with NPM1(mut) AML eligible for allogeneic SCT in a donor versus no-donor analysis. PATIENTS AND METHODS: Of 1,179 patients with AML (age 18 to 60 years) treated in the Study Alliance Leukemia AML 2003 trial, we identified all NPM1(mut) patients with an intermediate-risk karyotype. According to the trial protocol, patients were intended to receive an allogeneic SCT if an HLA-identical sibling donor was available. Patients with no available donor received consolidation or autologous SCT. We compared relapse-free survival (RFS) and overall survival (OS) depending on the availability of a suitable donor. RESULTS: Of 304 eligible patients, 77 patients had a sibling donor and 227 had no available matched family donor. The 3-year RFS rates in the donor and no-donor groups were 71% and 47%, respectively (P = .005); OS rates were 70% and 60%, respectively (P = .114). In patients with normal karyotype and no FLT3 internal tandem duplication (n = 148), the 3-year RFS rates in the donor and no-donor groups were 83% and 53%, respectively (P = .004); and the 3-year OS rates were 81% and 75%, respectively (P = .300). CONCLUSION: Allogeneic SCT led to a significantly prolonged RFS in patients with NPM1(mut) AML. The absence of a statistically significant difference in OS is most likely a result of the fact that NPM1(mut) patients who experienced relapse responded well to salvage treatment. Allogeneic SCT in first remission has potent antileukemic efficacy and is a valuable treatment option in patients with NPM1(mut) AML with a sibling donor.
PURPOSE: The presence of a mutated nucleophosmin-1 gene (NPM1(mut)) in acute myeloid leukemia (AML) is associated with a favorable prognosis. To assess the predictive value with regard to allogeneic stem-cell transplantation (SCT), we compared the clinical course of patients with NPM1(mut) AML eligible for allogeneic SCT in a donor versus no-donor analysis. PATIENTS AND METHODS: Of 1,179 patients with AML (age 18 to 60 years) treated in the Study Alliance Leukemia AML 2003 trial, we identified all NPM1(mut) patients with an intermediate-risk karyotype. According to the trial protocol, patients were intended to receive an allogeneic SCT if an HLA-identical sibling donor was available. Patients with no available donor received consolidation or autologous SCT. We compared relapse-free survival (RFS) and overall survival (OS) depending on the availability of a suitable donor. RESULTS: Of 304 eligible patients, 77 patients had a sibling donor and 227 had no available matched family donor. The 3-year RFS rates in the donor and no-donor groups were 71% and 47%, respectively (P = .005); OS rates were 70% and 60%, respectively (P = .114). In patients with normal karyotype and no FLT3 internal tandem duplication (n = 148), the 3-year RFS rates in the donor and no-donor groups were 83% and 53%, respectively (P = .004); and the 3-year OS rates were 81% and 75%, respectively (P = .300). CONCLUSION: Allogeneic SCT led to a significantly prolonged RFS in patients with NPM1(mut) AML. The absence of a statistically significant difference in OS is most likely a result of the fact that NPM1(mut) patients who experienced relapse responded well to salvage treatment. Allogeneic SCT in first remission has potent antileukemic efficacy and is a valuable treatment option in patients with NPM1(mut) AML with a sibling donor.
Authors: J R Passweg; M Labopin; J Cornelissen; L Volin; G Socié; A Huynh; R Tabrizi; D Wu; C Craddock; N Schaap; J Kuball; P Chevallier; J Y Cahn; D Blaise; A Ghavamzadeh; K Bilger; F Ciceri; C Schmid; S Giebel; A Nagler; M Mohty Journal: Bone Marrow Transplant Date: 2015-06-01 Impact factor: 5.483
Authors: J Versluis; F E M In 't Hout; R Devillier; W L J van Putten; M G Manz; M-C Vekemans; M-C Legdeur; J R Passweg; J Maertens; J Kuball; B J Biemond; P J M Valk; B A van der Reijden; G Meloni; H C Schouten; E Vellenga; T Pabst; R Willemze; B Löwenberg; G Ossenkoppele; F Baron; G Huls; J J Cornelissen Journal: Leukemia Date: 2016-06-24 Impact factor: 11.528
Authors: Sanjay S Patel; Frank C Kuo; Christopher J Gibson; David P Steensma; Robert J Soiffer; Edwin P Alyea; Yi-Bin A Chen; Amir T Fathi; Timothy A Graubert; Andrew M Brunner; Martha Wadleigh; Richard M Stone; Daniel J DeAngelo; Valentina Nardi; Robert P Hasserjian; Olga K Weinberg Journal: Blood Date: 2018-05-03 Impact factor: 22.113