Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) genes occur in about 20% patients with acute myeloid leukemia (AML), leading to DNA hypermethylation and epigenetic deregulation. We assessed the prognostic significance of IDH1/2 mutations (IDH1/2+) in 398 AML patients with normal karyotype (NK-AML), treated with daunorubicine + cytarabine (DA), DA + cladribine (DAC), or DA + fludarabine. IDH2 mutation was an independent favorable prognostic factor for 4-year overall survival (OS) in total NK-AML population (p = 0.03, censoring at allotransplant). We next evaluated the effect of addition of cladribine to induction regimen on the patients’ outcome according to IDH1/2 mutation status. In DAC group, 4-year OS was increased in IDH2+ patients, compared to IDH-wild type group (54% vs 33%; p = 0.0087, censoring at allotransplant), while no difference was observed for DA-treated subjects. In multivariate analysis, DAC independently improved the survival of IDH2+ patients (HR = 0.6 [0.37–0.93]; p = 0.024; censored at transplant), indicating that this group specifically benefits from cladribine-containing therapy. In AML cells with R140Q or R172K IDH2 mutations, cladribine restrained mutations-related DNA hypermethylation. Altogether, DAC regimen produces better outcomes in IDH2+ NK-AML patients than DA, and this likely results from the hypomethylating activity of cladribine. Our observations warrant further investigations of induction protocols combining cladribine with IDH1/2 inhibitors in IDH2-mutant.
Nowadays, the most important factors that cause global market activity and have a big infl uence on logistics processes are: globalisation and rapid development of new technologies. In that environment, military logistics are operating incessantly alongside the supply of goods in times of war, peace and crisis. Th ese logistics are focused on fi nding solutions for being more eff ective and economically profi table. Because of this, logisticians try to reduce costs and supply good faster, as well as trying to provide the right quality and service.. Th e current challenges in military logistics support have changed. Th e biggest challenge for all logistics processes is to provide services according to the 7R formula (right time, right product, right quantity, right condition, right place, right customer, and right price). A logistics leader is important for every operational mission. Th anks to the leader making quick and smart decisions, successful termination of a mission is possible. Th e article is based on the example of logistics support for the Polish contingent in Kosovo. In the light of the above, the aim of the article is to identify and estimate the situation of military logistics. Th e research problem is as follow: What are the biggest determinants of logistics processes in military area?
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