Originally published as JCO Early Release 10.1200/JCO.2007.15.4245 on December 1 2008

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Age-Related Risk Profile and Chemotherapy Dose Response in Acute Myeloid Leukemia: A Study by the German Acute Myeloid Leukemia Cooperative Group

Thomas Büchner, Wolfgang E. Berdel, Claudia Haferlach, Torsten Haferlach, Susanne Schnittger, Carsten Müller-Tidow, Jan Braess, Karsten Spiekermann, Joachim Kienast, Peter Staib, Andreas Grüneisen, Wolfgang Kern, Albrecht Reichle, Georg Maschmeyer, Carlo Aul, Eva Lengfelder, Maria-Cristina Sauerland, Achim Heinecke, Bernhard Wörmann, Wolfgang Hiddemann

From the Departments of Hematology and Oncology and Medical Informatics and Biomathematics, University of Münster, Münster; Munich Leukemia Laboratory; Department of Internal Medicine III, University of Munich, Munich; Clinic I Internal Medicine, University of Cologne, Cologne; Department of Hematology and Oncology, Municipal Hospital Neukölln, Berlin; Department of Hematology and Oncology, University of Regensburg, Regensburg; Department of Hematology and Oncology, Medical Center Ernst von Bergmann, Potsdam; Department of Hematology and Oncology, St Johannes Hospital, Duisburg; Department of Hematology and Oncology, University of Mannheim, Mannheim; Department of Hematology and Oncology, Municipal Hospital, Braunschweig; and Clinical Cooperative Group "Acute Leukemia" of the Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany

Corresponding author: Thomas Büchner, MD, PhD, University of Münster, Department of Hematology/Oncology, Albert-Schweitzer-Str 33, 48129 Münster, Germany; e-mail: buechnr{at}uni-muenster.de

Purpose The purpose of the study was to assess the contribution of age and disease variables to the outcome of untreated patients with acute myeloid leukemia (AML) receiving varying intensive induction chemotherapy.

Patients and Methods Patients 16 to 85 years of age with primary AML, known karyotype, and uniform postremission chemotherapy enrolled onto two consecutive trials were eligible and were randomly assigned to induction either with a standard-dose (cytarabine, daunorubicin, and 6-thioguanine) and a high-dose (cytarabine and mitoxantrone) combination, or with two courses of the high-dose combination. Subgroups were defined by karyotype, nucleophosmin and FLT3 mutation, WBC count, serum lactate dehydrogenase, and residual blasts.

Results In 1,284 patients, the overall survival at 4 years in those younger and older than 60 years was 37% versus 16% (P < .001) and the ongoing remission duration was 46% versus 22% (P < .001). Similar age-related differences in outcome were found for all defined subgroups. No difference in outcome according to randomly assigned treatment regimen was observed in any age group or prognostic subset. Regarding prognostic subgroups, molecular factors were also considered.

Conclusion Under harmonized conditions, older and younger patients with AML show modest differences in their risk profiles and equally no dose response to intensified chemotherapy. Their observed fundamental difference in outcome across all subgroups remains unexplained. Further molecular investigation may elucidate the age effect in AML and identify new targets.

published online ahead of print at www.jco.org on December 1, 2008

Supported by Grants No. M17/92/Bü1 and 70-2839-Bü4 from Deutsche Krebshilfe, Grant No. 01 GI 9976 from Bundesministerium Bildung und Forschung Competence Network Acute and Chronic Leukemias, Grant No. LSH-2002-2.2.0-3 from European Commission European LeukemiaNet, and an unrestricted grant from AMGEN.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00266136 [ClinicalTrials.gov]

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