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Prognosis of acute myeloid leukemia patients up to 60 years of age exhibiting trisomy 8 within a non-complex karyotype: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup

From Department of Internal Medicine I, University of Dresden, Germany (MS, TI, GE); Department of Internal Medicine III, University of Ulm, Germany (RF.S, HD); Department of Hematology/Oncology, University of Leipzig, Germany (HK.A-A, RK); Department of Hematology, Hemostasis and Oncology, Hannover Medical School, Germany (AG, JK); Department of Internal Medicine V, Klinikum Lüdenscheid, Germany (GH); Department of Medical Informatics and Biomathematics, University of Münster, Germany (CS); Department of Internal Medicine A, University of Münster, Germany (TB)

Correspondence: Markus Schaich, MD, Medizinische Klinik und Poliklinik I, Universitätsklinikum C.G.Carus, Fetscherstr. 74, 01307 Dresden, Germany. E-mail: markus.schaich{at}uniklinikum-dresden.de

Background and Objectives: Trisomy 8 (+8) is among the commonest genetic aberrations seen in acute myeloid leukemia (AML). However, the prognostic significance of this aberration and the best consolidation strategy for patients with it are still not resolved. Additional prognostic indicators are needed to further classify these patients and determine their appropriate management.

Design and Methods: Individual patient data-based meta-analysis was performed on 131 patients (median age 50 (18–60) years) with +8 as a sole aberration or +8 with one additional aberration treated between 1993 and 2002 in eight prospective German AML treatment trials. All patients received state-of-the-art treatment including high-dose cytarabine with the option for autologous or allogeneic hematopoietic stem cell transplantation (HSCT).

Results: In total, the 131 patients had a 3-year overall survival (OS) of 29% and a 3-year relapse-free survival (RFS) of 32%. Independent prognostic factors contributing to shorter OS were age 45 years, extramedullary disease, and a percentage of +8 positive metaphases 80%. Combining these three prognostic variables established a hierarchical model for OS. The 3-year OS was 13% for the high-risk group, 36% for the intermediate-risk group, and 55% for the low-risk group (p<0.0001). Age <45 years and allogeneic HSCT (as treated) were independent prognostic factors for longer RFS. Additional cytogenetic aberrations other than t(8;21), inv(16), t(16;16), t(15;17) or 11q23 had no influence on treatment outcome.

Interpretation and Conclusions: We provide a new prognostic model for risk stratification of AML patients with +8. The data indicate that allogeneic HSCT may prolong RFS compared to that achieved with other strategies of post-remission therapy.

Key words: acute myeloid leukemia, trisomy 8, treatment outcome, prognostic factors, post-remission therapy.