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Nael Alakel,1,* Friedrich Stölzel,1,* Brigitte Mohr,1 Michael Kramer,1 Uta Oelschlägel,1 Christoph Röllig,1 Martin Bornhäuser,1 Gerhard Ehninger,1 Markus Schaich2 1Department of Internal Medicine I, University Hospital Carl Gustav Carus at the Technische Universitaet Dresden, Dresden, 2Hematology, Oncology and Palliative Medicine, Rems-Murr-Klinikum, Winnenden, Germany *These authors contributed equally to this work Introduction: Acute myeloid leukemia (AML) rarely involves the central nervous system (CNS). Little is known about the clinical course in adult AML patients since most studies examined pediatric patients. Therefore, this study analyzed the data of patients treated in three prospective trials of the “Study Alliance Leukemia” (SAL) study group for CNS involvement.Methods: In all, 3,261 AML patients included in the prospective AML96, AML2003, and AML60+ trials of the SAL study group were analyzed. Symptomatic patients underwent cerebrospinal fluid (CSF) puncture and CNS involvement was diagnosed depending on morphology and/or flow cytometry of the CSF. Cytogenetic, molecular, clinical, and laboratory parameters were analyzed in order to identify risk factors.Results: A total of 55 patients had proven symptomatic CNS involvement. Significantly more patients revealed CNS involvement at relapse (34 patients, 2.9%) compared with first diagnosis (21 patients, 0.6%), p