Combined molecular and clinical prognostic index for relapse and survival in cytogenetically normal acute myeloid
Friederike Pastore1, Annika Dufour2, Tobias Benthaus2
1Friederike 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.
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.
