1. Combined molecular and clinical prognostic index for relapse and survival in cytogenetically normal acute myeloid leukemia
- Author
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Annika Dufour, Gudrun Mellert, Guido Marcucci, Eva Hoster, Kati Maharry, Bernhard J. Woermann, Wolfgang E. Berdel, Stefan K. Bohlander, Maria Cristina Sauerland, Michaela Feuring-Buske, Bianka Ksienzyk, Utz Krug, Stephanie Schneider, Evelyn Zellmeier, Christian Buske, Clara D. Bloomfield, Purvi M. Kakadia, Michael Unterhalt, Tobias Benthaus, Klaus H. Metzeler, Karsten Spiekermann, Achim Heinecke, Wolfgang Hiddemann, Thomas Buechner, Jan Braess, and Friederike Pastore
- Subjects
Oncology ,Male ,Cancer Research ,Myeloid ,Time Factors ,DNA Mutational Analysis ,Kaplan-Meier Estimate ,Recurrence ,Risk Factors ,Germany ,CEBPA ,Medicine ,Aged, 80 and over ,Age Factors ,Myeloid leukemia ,Nuclear Proteins ,ORIGINAL REPORTS ,Middle Aged ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Phenotype ,Treatment Outcome ,Cytogenetic Analysis ,Female ,Nucleophosmin ,Adult ,medicine.medical_specialty ,NPM1 ,Adolescent ,Risk Assessment ,Disease-Free Survival ,Decision Support Techniques ,Young Adult ,Predictive Value of Tests ,Internal medicine ,Humans ,Genetic Predisposition to Disease ,Aged ,Proportional Hazards Models ,Performance status ,business.industry ,Proportional hazards model ,Cancer ,Reproducibility of Results ,medicine.disease ,fms-Like Tyrosine Kinase 3 ,Immunology ,Mutation ,CCAAT-Enhancer-Binding Proteins ,business - 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.
- Published
- 2014