Clinical relevance of molecular aberrations in paediatric acute myeloid leukaemia at first relapse. (25th June 2014)

• Record Type: Journal Article
• Authors: Bachas, Costa; Schuurhuis, Gerrit Jan; Reinhardt, Dirk; Creutzig, Ursula; Kwidama, Zinia J.; Zwaan, C. Michel; van den Heuvel‐Eibrink, Marry M.; De Bont, Evelina S. J. M.; Elitzur, Sarah; Rizzari, Carmelo; de Haas, Valérie; Zimmermann, Martin; Cloos, Jacqueline; Kaspers, Gertjan J. L.
• Is Part Of: British journal of haematology. Volume 166:Number 6(2014:Sep.)
• Page Start: 902
• Page End: 910
• Publication Date: 2014-06-25
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12989
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh12989-abs-0001"> <title>Summary</title> <p>Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (<italic>FLT3</italic>, <italic> NRAS</italic>, <italic> KRAS</italic>, <italic> KIT</italic>, <italic> WT1</italic> and <italic>NPM1</italic> genes) at first relapse in a large set (<italic>n </italic>= 198) of relapsed non‐French‐American‐British M3, non‐Down syndrome AML patients that received similar relapse treatment. We correlated molecular aberrations with clinical and biological factors and studied their prognostic relevance. Hotspot mutations in the analysed genes were detected in 92 out of 198 patients (46·5%). In 72 of these 92 patients (78%), molecular aberrations were mutually exclusive for the currently analysed genes. <italic>FLT3</italic>‐internal tandem repeat (ITD) (18% of total group) mutations were most frequent, followed by <italic>NRAS</italic> (10·2%), <italic>KRAS</italic> (8%), <italic>WT1</italic> (8%), <italic>KIT</italic> (8%), <italic>NPM1</italic> (5%) and <italic>FLT3</italic>‐tyrosine kinase domain (3%) mutations. Presence of a <italic>WT1</italic> aberration was an independent risk factor for second relapse (Hazard Ratio [HR] = 2·74, <italic>P </italic>= 0·013). In patients who achieved second complete remission (70·2%), <italic>WT1</italic> and <italic>FLT3</italic>‐ITD aberrations were independent risk factors for poor overall survival (HR = 2·32, <italic>P </italic>= 0·038 and HR = 1·89, <italic>P </italic>= 0·045 respectively). These data show that molecular aberrations at first relapse are of prognostic relevance and potentially useful for risk group stratification of paediatric relapsed AML and for identification of patients eligible for personalized treatment.</p> </abstract>