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Clinical relevance of molecular aberrations in paediatric acute myeloid leukaemia at first relapse
Author(s) -
Bachas Costa,
Schuurhuis Gerrit Jan,
Reinhardt Dirk,
Creutzig Ursula,
Kwidama Zinia J.,
Zwaan C. Michel,
HeuvelEibrink Marry M.,
De Bont Evelina S. J. M.,
Elitzur Sarah,
Rizzari Carmelo,
Haas Valérie,
Zimmermann Martin,
Cloos Jacqueline,
Kaspers Gertjan J. L.
Publication year - 2014
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.12989
Subject(s) - neuroblastoma ras viral oncogene homolog , npm1 , kras , medicine , oncology , hazard ratio , gene , cancer , biology , genetics , confidence interval , colorectal cancer , karyotype , chromosome
Summary 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 ( FLT 3 , NRAS , KRAS , KIT , WT 1 and NPM 1 genes) at first relapse in a large set ( n = 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. FLT 3 ‐internal tandem repeat ( ITD ) (18% of total group) mutations were most frequent, followed by NRAS (10·2%), KRAS (8%), WT 1 (8%), KIT (8%), NPM 1 (5%) and FLT 3 ‐tyrosine kinase domain (3%) mutations. Presence of a WT 1 aberration was an independent risk factor for second relapse (Hazard Ratio [ HR ] = 2·74, P = 0·013). In patients who achieved second complete remission (70·2%), WT 1 and FLT 3 ‐ ITD aberrations were independent risk factors for poor overall survival ( HR = 2·32, P = 0·038 and HR = 1·89, P = 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.