title: TP53 mutation in patients with high-risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation.
abstract: Treatment success in patients with acute myeloid leukaemia (AML) is heterogeneous. Cytogenetic and molecular alterations are strong prognostic factors, which have been used to individualize treatment. Here, we studied the impact of TP53 mutations on the outcome of AML patients with adverse cytogenetic risk treated with allogeneic haematopoietic stem cell transplantation (HSCT). Samples of 97 patients with AML and adverse-risk cytogenetics who had received a HSCT within three randomized trials were analysed. Complete sequencing of the TP53 coding region was performed using next generation sequencing. The median age was 51 years. Overall, TP53 mutations were found in 40 patients (41%). With a median follow up of 67 months, the three-year probabilities of overall survival (OS) and event-free survival for patients with TP53 wild type were 33% [95% confidence interval (CI), 21% to 45%] and 24% (95% CI, 13% to 35%) compared to 10% (95% CI, 0% to 19%) and 8% (95% CI, 0% to 16%) (P = 0·002 and P = 0·007) for those with mutated TP53, respectively. In multivariate analysis, the TP53-mutation status had a negative impact on OS (Hazard Ratio = 1·7; P = 0·066). Mutational analysis of TP53 might be an important additional tool to predict outcome after HSCT in patients with adverse karyotype AML.
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Middeke
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.|Deutsches Konsortium für Translationale Krebsforschung Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Herold
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Rücker-Braun
authors.affiliation: Medizinische Klinik A, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Medizinische Klinik A, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelljes
authors.affiliation: Robert Bosch Hospital, Stuttgart, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kaufmann
authors.affiliation: Klinikum Nord, Nürnberg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schäfer-Eckart
authors.affiliation: Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Baldus
authors.affiliation: Asklepios Klinik St Georg, Hamburg, Germany.
authors.forename: Reingard
authors.initials: R
authors.lastname: Stuhlmann
authors.affiliation: Medizinische Klinik und Poliklinik, Abteilung Innere Medizin V, Hämatologie, Onkologie und Rheumatologie, Universität Heidelberg, Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Medizinische Klinik 5, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Wolf
authors.initials: W
authors.lastname: Rösler
authors.affiliation: Medizinische Klinik II, Klinikum der J.W. Goethe Universität, Frankfurt, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Serve
authors.affiliation: Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III, Chemnitz, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hänel
authors.affiliation: Kliniken für Innere Medizin, Hämatologie/Onkologie und Immunologie, Universitätsklinikum Marburg, Marburg, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Sohlbach
authors.affiliation: DKMS German Bone Marrow Donor Centre, Clinical Trials Unit, Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Klesse
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mohr
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Heidenreich
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Stölzel
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röllig
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.|Deutsches Konsortium für Translationale Krebsforschung Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.|DKMS German Bone Marrow Donor Centre, Clinical Trials Unit, Dresden, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm
keywords: TP53 mutation; acute myeloid leukaemia; allogeneic transplantation