BACKGROUND: Nucleophosmin (NPM1) and Flt3 internal tandem duplications (Flt3-ITD mutations) represent the most frequent molecular aberrations in patients with acute myeloid leukemia (AML). While NPM1 mutations are associated with favourable prognosis in younger AML patients, Flt3-ITD mutations reflect an unfavourable prognostic factor in these patients. So far, especially NPM1 mutations have not yet been evaluated exclusively in older patients. PATIENTS AND METHODS: We retrospectively analysed the prevalence of NPM1 and Flt3-ITD mutations and its association with complete remission (CR), and survival in 99 elderly patients (median age 71 yr, range 60-85 yr) newly diagnosed for AML. Primary treatment approach was curative in 54, and palliative in 38 patients, while seven patients received best supportive care only. The mean follow-up of surviving patients was 600 d. RESULTS: Sixty-seven patients were tested negative for NPM1 and Flt3-ITD mutations (group 1), 16 patients carried only a NPM1 mutation (group 2) and nine patients had only a Flt3-ITD mutation (group 3) while additional seven patients were positive for both aberrations (group 4). We can demonstrate a significant higher rate of CR comparing wildtype vs. NPM1 positive patients (40.5% for group 1 vs. 80.0% for group 2, P = 0.03) for patients receiving curative therapy. Interestingly, there is no significant difference in overall survival between group 1 and group 2 (Log-rank test P = 0.22, median 440 d vs. 1125 d). In contrast, patients carrying a Flt3-ITD mutation had a significant worse overall survival compared to wildtype patients (P = 0.03, median 210 d for group 3 + 4 vs. 634 d for group 1 + 2) while no difference of CR rate could be observed (42.8% vs. 48.9%, P = 0.91). CONCLUSION: As elderly but medically fit patients with AML carrying a NPM1 mutation have a high CR rate, age itself should not be a barrier for induction treatment. However, new therapeutic concepts of postremission therapy (e.g. allogeneic stem cell transplantation after dose-reduced conditioning) should be considered for these patients in first CR.
BACKGROUND:Nucleophosmin (NPM1) and Flt3 internal tandem duplications (Flt3-ITD mutations) represent the most frequent molecular aberrations in patients with acute myeloid leukemia (AML). While NPM1 mutations are associated with favourable prognosis in younger AMLpatients, Flt3-ITD mutations reflect an unfavourable prognostic factor in these patients. So far, especially NPM1 mutations have not yet been evaluated exclusively in older patients. PATIENTS AND METHODS: We retrospectively analysed the prevalence of NPM1 and Flt3-ITD mutations and its association with complete remission (CR), and survival in 99 elderly patients (median age 71 yr, range 60-85 yr) newly diagnosed for AML. Primary treatment approach was curative in 54, and palliative in 38 patients, while seven patients received best supportive care only. The mean follow-up of surviving patients was 600 d. RESULTS: Sixty-seven patients were tested negative for NPM1 and Flt3-ITD mutations (group 1), 16 patients carried only a NPM1 mutation (group 2) and nine patients had only a Flt3-ITD mutation (group 3) while additional seven patients were positive for both aberrations (group 4). We can demonstrate a significant higher rate of CR comparing wildtype vs. NPM1 positive patients (40.5% for group 1 vs. 80.0% for group 2, P = 0.03) for patients receiving curative therapy. Interestingly, there is no significant difference in overall survival between group 1 and group 2 (Log-rank test P = 0.22, median 440 d vs. 1125 d). In contrast, patients carrying a Flt3-ITD mutation had a significant worse overall survival compared to wildtype patients (P = 0.03, median 210 d for group 3 + 4 vs. 634 d for group 1 + 2) while no difference of CR rate could be observed (42.8% vs. 48.9%, P = 0.91). CONCLUSION: As elderly but medically fit patients with AML carrying a NPM1 mutation have a high CR rate, age itself should not be a barrier for induction treatment. However, new therapeutic concepts of postremission therapy (e.g. allogeneic stem cell transplantation after dose-reduced conditioning) should be considered for these patients in first CR.
Authors: P Boddu; K Takahashi; N Pemmaraju; N Daver; C B Benton; S Pierce; M Konopleva; F Ravandi; J Cortes; H Kantarjian; C D DiNardo Journal: Leukemia Date: 2017-07-28 Impact factor: 11.528
Authors: Heiko Becker; Guido Marcucci; Kati Maharry; Michael D Radmacher; Krzysztof Mrózek; Dean Margeson; Susan P Whitman; Yue-Zhong Wu; Sebastian Schwind; Peter Paschka; Bayard L Powell; Thomas H Carter; Jonathan E Kolitz; Meir Wetzler; Andrew J Carroll; Maria R Baer; Michael A Caligiuri; Richard A Larson; Clara D Bloomfield Journal: J Clin Oncol Date: 2009-12-21 Impact factor: 44.544
Authors: Fabiana Ostronoff; Megan Othus; Michelle Lazenby; Elihu Estey; Frederick R Appelbaum; Anna Evans; John Godwin; Amanda Gilkes; Kenneth J Kopecky; Alan Burnett; Alan F List; Min Fang; Vivian G Oehler; Stephen H Petersdorf; Era L Pogosova-Agadjanyan; Jerald P Radich; Cheryl L Willman; Soheil Meshinchi; Derek L Stirewalt Journal: J Clin Oncol Date: 2015-02-23 Impact factor: 44.544
Authors: Gunnar Juliusson; Martin Jädersten; Stefan Deneberg; Sören Lehmann; Lars Möllgård; Lovisa Wennström; Petar Antunovic; Jörg Cammenga; Fryderyk Lorenz; Emma Ölander; Vladimir Lj Lazarevic; Martin Höglund Journal: Blood Adv Date: 2020-03-24