MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin
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Juliette Lambert1, Jérôme Lambert2, Olivier Nibourel3, Cécile Pautas4, Sandrine Hayette5, Jean-Michel Cayuela6, Christine Terré7, Philippe Rousselot1, Hervé Dombret8, Sylvie Chevret9, Claude Preudhomme3, Sylvie Castaigne1 and Aline Renneville3
1 Department of Hematology, Hôpital de Versailles, Le Chesnay, Université de Versailles-Saint Quentin; France
2 INSERM UMR-S 717, Paris; France
3 Laboratory of Hematology, CHRU de Lille; Université de Lille Nord de France, Inserm, U837, Team 3, Cancer Research Institute of Lille, Lille; France
4 Department of Hematology, Hôpital Henri Mondor, AP-HP, Créteil; France
5 Laboratory of Hematology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, UMR5239, Université Claude Bernard, Lyon; France
6 Laboratory of Hematology, Hôpital Saint-Louis, AP-HP, EA3518, University Paris Diderot, Paris; France
7 Laboratory of Cytogenetics, Hôpital de Versailles, Le Chesnay; France
8 Department of Hematology, Hôpital Saint Louis, AP-HP, Université Paris Diderot, EA 3518, Paris; France
9 Department of Informatics and Biostatistics, Hôpital Saint Louis, Université Paris Diderot, INSERM S 717, Paris; France
Juliette Lambert, email:
Keywords: minimal residual disease, gemtuzumab ozogamicin, acute myeloid leukemia, WT1 expression, NPM1 mutation
Received: May 13, 2014 Accepted: July 07, 2014 Published: July 09, 2014
We analysed the prognostic significance of minimal residual disease (MRD) level in adult patients with acute myeloid leukemia (AML) treated in the randomized gemtuzumab ozogamicin (GO) ALFA-0701 trial.
Levels of WT1 and NPM1 gene transcripts were assessed using cDNA-based real-time quantitative PCR in 183 patients with WT1 overexpression and in 77 patients with NMP1 mutation (NPM1mut) at diagnosis.
Positive WT1 MRD (defined as > 0.5% in the peripheral blood) after induction and at the end of treatment were both significantly associated with a higher risk of relapse and a shorter overall survival (OS). Positive NPM1mut MRD (defined as > 0.1% in the bone marrow) after induction and at the end of treatment also predicted a higher risk of relapse, but did not influence OS. Interestingly, the achievement of a negative NPM1mut MRD was significantly more frequent in patients treated in the GO arm compared to those treated in control arm (39 % versus 7% (p=0.006) after induction and 91% versus 61% (p=0.028) at the end of treatment). However, GO did not influence WT1 MRD levels.
Our study supports the prognostic significance of MRD assessed by WT1 and NPM1mut transcript levels and show that NPM1 MRD is decreased by GO treatment.
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