Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia: independent favorable prognostic factor within NPM1 mutated patients
Abstract We and others have shown that cytogenetically normal (CN)-AML patients with biallelic CEBPA gene mutations (biCEBPA) represent a molecularly distinct group with a favorable prognosis. Patients carrying a monoallelic CEBPA mutation (moCEBPA), however, show no different outcome compared to patients with wildtype CEBPA, and these mutations are frequently associated with mutated NPM1 or FLT3-ITD. So far, no molecular or clinical hallmark has been identified to prognostically distinguish moCEBPA patients from patients with wildtype CEBPA. Therefore, we used the data of 663 CN-AML patients treated within the AMLCG 1999 trial to explore the prognostic value of moCEBPA in the context of concomitant clinical and molecular markers (mutated NPM1, FLT3-ITD). Multiple Cox regression in 515 patients adjusting for all available potential confounders revealed that the NPM1 mutation modified the prognostic value of moCEBPA with respect to overall survival (OS, p = 0.017) and event-free survival (EFS, p = 0.011). MoCEBPA was beneficial in NPM1 mutated patients: adjusted OS–hazard ratio (HR) 0.09, 95% confidence interval (CI) 0.01–0.63, p = 0.016; EFS–HR (95% CI) 0.16 (0.04–0.65), p = 0.010. In contrast, moCEBPA had no prognostic impact in patients with wildtype NPM1: OS–HR (95% CI) 1.08 (0.59–1.97), p = 0.804; EFS–HR (95% CI) 1.12 (0.64–1.96), p = 0.682. We found no prognostic effect modification for moCEBPA by FLT3-ITD. The presence of a moCEBPA mutation was shown to be associated with prolonged survival in NPM1 mutated CN-AML patients. Confirmation of these results in larger studies will clarify whether an additional moCEBPA mutation influences the risk stratification of patients with an NPM1 mutated/FLT3-ITD positive genotype..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:91 |
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| Enthalten in: |
Annals of hematology - 91(2012), 7 vom: 24. Feb., Seite 1051-1063 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dufour, Annika [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Acute myeloid leukemia |
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| Anmerkungen: |
© Springer-Verlag 2012 |
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| doi: |
10.1007/s00277-012-1423-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia: independent favorable prognostic factor within NPM1 mutated patients |
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| 520 | |a Abstract We and others have shown that cytogenetically normal (CN)-AML patients with biallelic CEBPA gene mutations (biCEBPA) represent a molecularly distinct group with a favorable prognosis. Patients carrying a monoallelic CEBPA mutation (moCEBPA), however, show no different outcome compared to patients with wildtype CEBPA, and these mutations are frequently associated with mutated NPM1 or FLT3-ITD. So far, no molecular or clinical hallmark has been identified to prognostically distinguish moCEBPA patients from patients with wildtype CEBPA. Therefore, we used the data of 663 CN-AML patients treated within the AMLCG 1999 trial to explore the prognostic value of moCEBPA in the context of concomitant clinical and molecular markers (mutated NPM1, FLT3-ITD). Multiple Cox regression in 515 patients adjusting for all available potential confounders revealed that the NPM1 mutation modified the prognostic value of moCEBPA with respect to overall survival (OS, p = 0.017) and event-free survival (EFS, p = 0.011). MoCEBPA was beneficial in NPM1 mutated patients: adjusted OS–hazard ratio (HR) 0.09, 95% confidence interval (CI) 0.01–0.63, p = 0.016; EFS–HR (95% CI) 0.16 (0.04–0.65), p = 0.010. In contrast, moCEBPA had no prognostic impact in patients with wildtype NPM1: OS–HR (95% CI) 1.08 (0.59–1.97), p = 0.804; EFS–HR (95% CI) 1.12 (0.64–1.96), p = 0.682. We found no prognostic effect modification for moCEBPA by FLT3-ITD. The presence of a moCEBPA mutation was shown to be associated with prolonged survival in NPM1 mutated CN-AML patients. Confirmation of these results in larger studies will clarify whether an additional moCEBPA mutation influences the risk stratification of patients with an NPM1 mutated/FLT3-ITD positive genotype. | ||
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| 700 | 1 | |a Schneider, Friederike |4 aut | |
| 700 | 1 | |a Hoster, Eva |4 aut | |
| 700 | 1 | |a Benthaus, Tobias |4 aut | |
| 700 | 1 | |a Ksienzyk, Bianka |4 aut | |
| 700 | 1 | |a Schneider, Stephanie |4 aut | |
| 700 | 1 | |a Kakadia, Purvi M. |4 aut | |
| 700 | 1 | |a Sauerland, Maria-Cristina |4 aut | |
| 700 | 1 | |a Berdel, Wolfgang E. |4 aut | |
| 700 | 1 | |a Büchner, Thomas |4 aut | |
| 700 | 1 | |a Wörmann, Bernhard |4 aut | |
| 700 | 1 | |a Braess, Jan |4 aut | |
| 700 | 1 | |a Subklewe, Marion |4 aut | |
| 700 | 1 | |a Hiddemann, Wolfgang |4 aut | |
| 700 | 1 | |a Bohlander, Stefan K. |4 aut | |
| 700 | 1 | |a Spiekermann, Karsten |4 aut | |
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