Real-Life Management of FLT3-Mutated AML: Single-Centre Experience over 24 Years.

We analyzed 140 patients with a median age of 51 years; 21% had WBC ≥ 100 × 109/L, and 52% had an NPM1 co-mutation. Until 2018, 101 patients received chemotherapy; thereafter, 39 received 3+7+midostaurin. The overall CR rate was 64%, higher in NPM1 mutant patients (73%). Univariate analysis showed that NPM1 mutation (p = 0.032) and WBC < 100 × 109/L (p = 0.013) positively influenced the response, with a trend for FLT3i administration (p = 0.052). Multivariate analysis confirmed WBC count as an independent prognostic factor (p = 0.017). In CR1, 41/90 patients underwent allogeneic and 18 autologous transplantation. The median EFS was 1.1 vs. 1.6 years in autografted and allografted patients, respectively (p = 0.9). The one-year non-relapse mortality was 0.00% for autologous and 28% for allogeneic transplants (p = 0.007); CIR at 1 and 3 years was higher in autologous transplants (39% vs. 15% and 57% vs. 21%, p = 0.004). The median survival was not reached in the FLT3i group. Overall, 69 patients received stem cell transplantation (18 autologous, 51 allogeneic). Post-transplant FLT3i was resumed in eight patients, all alive after a median of 65 months. Allogeneic transplantation is crucial in FLT3-mutated AML, but the next challenge will be to identify which patients can benefit from transplants in CR1 and in which to intensify post-transplant therapy.

Cotinine levels influence the risk of rupture of brain aneurysms.

Cotinine, the primary metabolite of nicotine, is currently regarded as the best biomarker of tobacco smoke exposure. We aim to assess whether cotinine levels are associated with (1) intracranial aneurysm and (2) intracranial aneurysm rupture. METHODS: We performed a single-center case-control study. Cases were consecutive patients admitted with diagnosis of brain aneurysm (ruptured or unruptured). We randomly selected controls without intracranial aneurysm from the same source population that produced the cases. Smoking data were collected by questionnaire, and serum levels of cotinine were used as an objective measure of nicotine exposure. Logistic regression models were used to assess the relationship between cotinine levels and aneurysm rupture. RESULTS: We included 86 patients with intracranial aneurysm and 96 controls. Smoking status (p < .001), cotinine levels (p = .009), and female sex (p = .006) were associated with diagnosis of intracranial aneurysm. In the multivariate analysis, controlling for sex, smoker status and age, levels of cotinine were independently associated with aneurysm rupture (OR 1.53, 95% CI 1.10-2.13, p = .012). CONCLUSIONS: Our results suggest that high cotinine levels in smokers with brain aneurysm are significantly associated with high rupture risk, independently of smoker status, age, and sex.