Friederike Pastore1, Annika Dufour2, Tobias Benthaus2, Klaus H Metzeler2, Kati S Maharry2, Stephanie Schneider2, Bianka Ksienzyk2, Gudrun Mellert2, Evelyn Zellmeier2, Purvi M Kakadia2, Michael Unterhalt2, Michaela Feuring-Buske2, Christian Buske2, Jan Braess2, Maria Cristina Sauerland2, Achim Heinecke2, Utz Krug2, Wolfgang E Berdel2, Thomas Buechner2, Bernhard Woermann2, Wolfgang Hiddemann2, Stefan K Bohlander2, Guido Marcucci2, Karsten Spiekermann2, Clara D Bloomfield2, Eva Hoster2. 1. Friederike Pastore, Annika Dufour, Tobias Benthaus, Klaus H. Metzeler, Stephanie Schneider, Bianka Ksienzyk, Gudrun Mellert, Evelyn Zellmeier, Purvi M. Kakadia, Michael Unterhalt, Wolfgang Hiddemann, Stefan K. Bohlander, Karsten Spiekermann, and Eva Hoster, University Hospital Munich Großhadern; Friederike Pastore, Klaus H. Metzeler, Wolfgang Hiddemann, Stefan K. Bohlander, and Karsten Spiekermann, Helmholtz Center Munich; Eva Hoster, University of Munich, Munich; Purvi M. Kakadia and Stefan K. Bohlander, University Hospital Marburg, Marburg; Michaela Feuring-Buske, University Hospital Ulm; Christian Buske, Comprehensive Cancer Center Ulm, University of Ulm, Ulm; Jan Braess, Klinikum Barmherzige Brüder, Regensburg; Maria Cristina Sauerland and Achim Heinecke, University of Muenster; Utz Krug, Wolfgang E. Berdel, and Thomas Buechner, University Hospital Muenster, Muenster; Bernhard Woermann, German Society of Hematology and Oncology, Berlin, Germany; Kati S. Maharry, Guido Marcucci, and Clara D. Bloomfield, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Kati S. Maharry, Mayo Clinic, Rochester, MN; and Stefan K. Bohlander, University of Auckland, Auckland, New Zealand. friederike.pastore@med.uni-muenchen.de. 2. Friederike Pastore, Annika Dufour, Tobias Benthaus, Klaus H. Metzeler, Stephanie Schneider, Bianka Ksienzyk, Gudrun Mellert, Evelyn Zellmeier, Purvi M. Kakadia, Michael Unterhalt, Wolfgang Hiddemann, Stefan K. Bohlander, Karsten Spiekermann, and Eva Hoster, University Hospital Munich Großhadern; Friederike Pastore, Klaus H. Metzeler, Wolfgang Hiddemann, Stefan K. Bohlander, and Karsten Spiekermann, Helmholtz Center Munich; Eva Hoster, University of Munich, Munich; Purvi M. Kakadia and Stefan K. Bohlander, University Hospital Marburg, Marburg; Michaela Feuring-Buske, University Hospital Ulm; Christian Buske, Comprehensive Cancer Center Ulm, University of Ulm, Ulm; Jan Braess, Klinikum Barmherzige Brüder, Regensburg; Maria Cristina Sauerland and Achim Heinecke, University of Muenster; Utz Krug, Wolfgang E. Berdel, and Thomas Buechner, University Hospital Muenster, Muenster; Bernhard Woermann, German Society of Hematology and Oncology, Berlin, Germany; Kati S. Maharry, Guido Marcucci, and Clara D. Bloomfield, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Kati S. Maharry, Mayo Clinic, Rochester, MN; and Stefan K. Bohlander, University of Auckland, Auckland, New Zealand.
Abstract
PURPOSE:Cytogenetically normal (CN) acute myeloid leukemia (AML) is the largest and most heterogeneous cytogenetic AML subgroup. For the practicing clinician, it is difficult to summarize the prognostic information of the growing number of clinical and molecular markers. Our purpose was to develop a widely applicable prognostic model by combining well-established pretreatment patient and disease characteristics. PATIENTS AND METHODS: Two prognostic indices for CN-AML (PINA), one regarding overall survival (OS; PINAOS) and the other regarding relapse-free survival (RFS; PINARFS), were derived from data of 572 patients with CN-AML treated within the AML Cooperative Group 99 study (www.aml-score.org). RESULTS: On the basis of age (median, 60 years; range, 17 to 85 years), performance status, WBC count, and mutation status of NPM1, CEBPA, and FLT3-internal tandem duplication, patients were classified into the following three risk groups according to PINAOS and PINARFS: 29% of all patients and 32% of 381 responding patients had low-risk disease (5-year OS, 74%; 5-year RFS, 55%); 56% of all patients and 39% of responding patients had intermediate-risk disease (5-year OS, 28%; 5-year RFS, 27%), and 15% of all patients and 29% of responding patients had high-risk disease (5-year OS, 3%; 5-year RFS, 5%), respectively. PINAOS and PINARFS stratified outcome within European LeukemiaNet genetic groups. Both indices were confirmed on independent data from Cancer and Leukemia Group B/Alliance trials. CONCLUSION: We have developed and validated, to our knowledge, the first prognostic indices specifically designed for adult patients of all ages with CN-AML that combine well-established molecular and clinical variables and that are easily applicable in routine clinical care. The integration of both clinical and molecular markers could provide a basis for individualized patient care through risk-adapted therapy of CN-AML.
RCT Entities:
PURPOSE: Cytogenetically normal (CN) acute myeloid leukemia (AML) is the largest and most heterogeneous cytogenetic AML subgroup. For the practicing clinician, it is difficult to summarize the prognostic information of the growing number of clinical and molecular markers. Our purpose was to develop a widely applicable prognostic model by combining well-established pretreatment patient and disease characteristics. PATIENTS AND METHODS: Two prognostic indices for CN-AML (PINA), one regarding overall survival (OS; PINAOS) and the other regarding relapse-free survival (RFS; PINARFS), were derived from data of 572 patients with CN-AML treated within the AML Cooperative Group 99 study (www.aml-score.org). RESULTS: On the basis of age (median, 60 years; range, 17 to 85 years), performance status, WBC count, and mutation status of NPM1, CEBPA, and FLT3-internal tandem duplication, patients were classified into the following three risk groups according to PINAOS and PINARFS: 29% of all patients and 32% of 381 responding patients had low-risk disease (5-year OS, 74%; 5-year RFS, 55%); 56% of all patients and 39% of responding patients had intermediate-risk disease (5-year OS, 28%; 5-year RFS, 27%), and 15% of all patients and 29% of responding patients had high-risk disease (5-year OS, 3%; 5-year RFS, 5%), respectively. PINAOS and PINARFS stratified outcome within European LeukemiaNet genetic groups. Both indices were confirmed on independent data from Cancer and Leukemia Group B/Alliance trials. CONCLUSION: We have developed and validated, to our knowledge, the first prognostic indices specifically designed for adult patients of all ages with CN-AML that combine well-established molecular and clinical variables and that are easily applicable in routine clinical care. The integration of both clinical and molecular markers could provide a basis for individualized patient care through risk-adapted therapy of CN-AML.
Authors: Thomas Büchner; Wolfgang E Berdel; Claudia Schoch; Torsten Haferlach; Hubert L Serve; Joachim Kienast; Susanne Schnittger; Wolfgang Kern; Joelle Tchinda; Albrecht Reichle; Eva Lengfelder; Peter Staib; Wolf-Dieter Ludwig; Carlo Aul; Hartmut Eimermacher; Leopold Balleisen; Maria-Cristina Sauerland; Achim Heinecke; Bernhard Wörmann; Wolfgang Hiddemann Journal: J Clin Oncol Date: 2006-06-01 Impact factor: 44.544
Authors: Frederik Damm; Michael Heuser; Michael Morgan; Katharina Wagner; Kerstin Görlich; Anika Grosshennig; Iyas Hamwi; Felicitas Thol; Ewa Surdziel; Walter Fiedler; Michael Lübbert; Lothar Kanz; Christoph Reuter; Gerhard Heil; Ruud Delwel; Bob Löwenberg; Peter J M Valk; Jürgen Krauter; Arnold Ganser Journal: Blood Date: 2011-03-03 Impact factor: 22.113
Authors: Utz Krug; Christoph Röllig; Anja Koschmieder; Achim Heinecke; Maria Cristina Sauerland; Markus Schaich; Christian Thiede; Michael Kramer; Jan Braess; Karsten Spiekermann; Torsten Haferlach; Claudia Haferlach; Steffen Koschmieder; Christian Rohde; Hubert Serve; Bernhard Wörmann; Wolfgang Hiddemann; Gerhard Ehninger; Wolfgang E Berdel; Thomas Büchner; Carsten Müller-Tidow Journal: Lancet Date: 2010-12-03 Impact factor: 79.321
Authors: E J Lee; S L George; M Caligiuri; T P Szatrowski; B L Powell; S Lemke; R K Dodge; R Smith; M Baer; C A Schiffer Journal: J Clin Oncol Date: 1999-09 Impact factor: 44.544
Authors: P D Kottaridis; R E Gale; M E Frew; G Harrison; S E Langabeer; A A Belton; H Walker; K Wheatley; D T Bowen; A K Burnett; A H Goldstone; D C Linch Journal: Blood Date: 2001-09-15 Impact factor: 22.113
Authors: Bas J Wouters; Bob Löwenberg; Claudia A J Erpelinck-Verschueren; Wim L J van Putten; Peter J M Valk; Ruud Delwel Journal: Blood Date: 2009-01-26 Impact factor: 22.113
Authors: Sabine Kayser; Richard F Schlenk; Martina Correa Londono; Frank Breitenbuecher; Kerstin Wittke; Juan Du; Silja Groner; Daniela Späth; Jürgen Krauter; Arnold Ganser; Hartmut Döhner; Thomas Fischer; Konstanze Döhner Journal: Blood Date: 2009-07-14 Impact factor: 22.113
Authors: Keith Wheatley; Cassandra L Brookes; Andrew J Howman; Anthony H Goldstone; Donald W Milligan; Archibald G Prentice; Anthony V Moorman; Alan K Burnett Journal: Br J Haematol Date: 2009-03-26 Impact factor: 6.998
Authors: Fan Zhou; Fen Zhou; Mengyi Du; Lin Liu; Tao Guo; Linghui Xia; Runming Jin; Yu Hu; Heng Mei Journal: Int J Hematol Date: 2019-08-22 Impact factor: 2.490
Authors: Antonio R Lucena-Araujo; Juan L Coelho-Silva; Diego A Pereira-Martins; Douglas R Silveira; Luisa C Koury; Raul A M Melo; Rosane Bittencourt; Katia Pagnano; Ricardo Pasquini; Elenaide C Nunes; Evandro M Fagundes; Ana B Gloria; Fábio Kerbauy; Maria de Lourdes Chauffaille; Israel Bendit; Vanderson Rocha; Armand Keating; Martin S Tallman; Raul C Ribeiro; Richard Dillon; Arnold Ganser; Bob Löwenberg; P J M Valk; Francesco Lo-Coco; Miguel A Sanz; Nancy Berliner; Eduardo M Rego Journal: Blood Date: 2019-07-10 Impact factor: 22.113
Authors: Douglas R A Silveira; Lynn Quek; Itamar S Santos; Anna Corby; Juan L Coelho-Silva; Diego A Pereira-Martins; Grant Vallance; Benjamin Brown; Luciana Nardinelli; Wellington F Silva; Elvira D R P Velloso; Antonio R Lucena-Araujo; Fabiola Traina; Andy Peniket; Paresh Vyas; Eduardo M Rego; Israel Bendit; Vanderson Rocha Journal: Blood Adv Date: 2020-05-26
Authors: A Sureda; P Bader; S Cesaro; P Dreger; R F Duarte; C Dufour; J H F Falkenburg; D Farge-Bancel; A Gennery; N Kröger; F Lanza; J C Marsh; A Nagler; C Peters; A Velardi; M Mohty; A Madrigal Journal: Bone Marrow Transplant Date: 2015-03-23 Impact factor: 5.483