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TP 53 mutation in patients with high‐risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation
Author(s) -
Middeke Jan M.,
Herold Sylvia,
RückerBraun Elke,
Berdel Wolfgang E.,
Stelljes Matthias,
Kaufmann Martin,
SchäferEckart Kerstin,
Baldus Claudia D.,
Stuhlmann Reingard,
Ho Anthony D.,
Einsele Hermann,
Rösler Wolf,
Serve Hubert,
Hänel Mathias,
Sohlbach Kristina,
Klesse Christian,
Mohr Brigitte,
Heidenreich Falk,
Stölzel Friedrich,
Röllig Christoph,
Platzbecker Uwe,
Ehninger Gerhard,
Bornhäuser Martin,
Thiede Christian,
Schetelig Johannes
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13912
Subject(s) - medicine , hazard ratio , transplantation , hematopoietic stem cell transplantation , oncology , stem cell , adverse effect , cytogenetics , haematopoiesis , confidence interval , gastroenterology , biology , genetics , chromosome , gene
Summary 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 TP 53 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 TP 53 coding region was performed using next generation sequencing. The median age was 51 years. Overall, TP 53 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 TP 53 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 TP 53, respectively. In multivariate analysis, the TP 53 ‐mutation status had a negative impact on OS (Hazard Ratio = 1·7; P = 0·066). Mutational analysis of TP 53 might be an important additional tool to predict outcome after HSCT in patients with adverse karyotype AML .