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 Blood, 21 May 2009, Vol. 113, No. 21, pp. 5250-5253.
Prepublished online as a Blood First Edition Paper on March 11, 2009; DOI 10.1182/blood-2008-09-172668.

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MYELOID NEOPLASIA

Brief report

NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS)

Friederike Schneider1, Eva Hoster1, Michael Unterhalt1, Stephanie Schneider1, Annika Dufour1, Tobias Benthaus1, Gudrun Mellert1, Evelin Zellmeier1, Stefan K. Bohlander1,2, Michaela Feuring-Buske1,2, Christian Buske1,2, Jan Braess1, Susanne Fritsch1, Achim Heinecke3, Maria C. Sauerland3, Wolfgang E. Berdel4, Thomas Buechner4, Bernhard J. Woermann5, Wolfgang Hiddemann1,2, and Karsten Spiekermann1,2

1 Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital Munich, Munich; 2 Clinical Cooperative Group Acute Leukemias, Helmholtz Center Munich, Munich; 3 Department of Medical Informatics and Biomathematics, and 4 Department of Medicine, Hematology and Oncology, University of Muenster, Muenster; and 5 Klinikum Braunschweig, Braunschweig, Germany

Mutations in the NPM1 gene represent the most frequent genetic alterations in patients with acute myeloid leukemia (AML) and are associated with a favorable outcome. In 690 normal karyotype (NK) AML patients the complete remission rates (CRs) and the percentage of patients with adequate in vivo blast cell reduction 1 week after the end of the first induction cycle were significantly higher in NPM1+ (75% and 80%, respectively) than in NPM1– (57% and 57%, respectively) patients, but were unaffected by the FLT3-ITD status. Multivariate analyses revealed the presence of a NPM1 mutation as an independent positive prognostic factor for the achievement of an adequate day-16 blast clearance and a CR. In conclusion, NPM1+ blast cells show a high in vivo sensitivity toward induction chemotherapy irrespective of the FLT3-ITD mutation status. These findings provide insight into the pathophysiology and help to understand the favorable clinical outcome of patients with NPM1+ AML.


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