Symptomatic central nervous system involvement in adult patients with acute myeloid leukemia

Abstract

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<0.001. CNS involvement at initial diagnosis had a significantly higher frequency in patients with complex aberrant karyotypes, high serum lactate dehydrogenase activity, French–American–British M5 subtype, FLT3–internal tandem duplication (ITD) mutations alone, and co-occurrence of a FLT3–ITD and NPM1 mutation. Furthermore, AML patients with CNS involvement at diagnosis had an inferior outcome compared with patients without CNS involvement even if treated with intrathecal chemotherapy with an overall survival of 11% versus 30% at 5 years, p=0.004.Conclusion: This study analyzed the largest data set of adult AML patients with proven CNS involvement reported so far. The data demonstrated very low prevalence of CNS involvement at initial diagnosis in adult patients with AML, and described new risk factors. In patients with risk factors, intense diagnostic and treatment strategies should be employed in the future. Keywords: Meningeal leukemia, CNS-involvement, cerebrospinal fluid, extramedullary leukemia

Keywords

• Acute myeloid leukemia
• Central nervous system
• meningeal leukemia