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Simple Summary: In older AML patients, their clinical fitness is of utmost importance for choosing the most appropriate therapy. Therefore, treatment-specific fitness criteria were devised in 2013 by SIE/SIES/GITMO to select patients deemed unfit for intensive chemotherapy (ICT) or even hypomethylating agents (HMAs). Since then, the therapeutic armamentarium for patients unfit for ICT has been enriched. In the present analysis of over 500 patients treated in REL centres, venetoclax/HMAs emerged as the most frequently used treatment. Considering its unique toxicity profile, an update of treatment-specific fitness criteria for selecting candidates for venetoclax/HMAs would be desirable. REL hematologists, who have gained experience with the combination over the last years, were asked if they actually restrict SIE/SIES/GITMO fitness criteria for HMAs when candidating patients to venetoclax/HMAs. A broad consensus emerged on limiting its choice to patients younger than 80–85, with a cardiac EF > 40%, without significant pulmonary comorbidities, and with an adequate caregiver. A retrospective survey was conducted in hematologic centres of the Rete Ematologica Lombarda (REL) on 529 older AML patients seen between 2020–2022. Compared to 2008–2016, the use of intensive chemotherapy (ICT) decreased from 40% to 18.1% and of hypomethylating agents (HMAs) from 19.5% to 13%, whereas the combination of Venetoclax/HMA, initially not available, increased from 0% to 36.7%. Objective treatment-specific fitness criteria proposed by SIE/SIES/GITMO in 2013 allow an appropriate choice between ICT and HMAs by balancing their efficacy and toxicity. Venetoclax/HMA, registered for patients unfit to ICT, has a unique toxicity profile because of prolonged granulocytopenia and increased infectious risk. Aiming at defining specific fitness criteria for the safe use of Venetoclax/HMA, a preliminary investigation was conducted among expert REL hematologists, asking for modifications of SIE/SIES/GITMO criteria they used to select candidates for Venetoclax/HMA. While opinions among experts varied, a general consensus emerged on restricting SIE/SIES/GITMO criteria for ICT-unfit patients to an age limit of 80–85, cardiac function > 40%, and absence of recurrent lung infections, bronchiectasis, or exacerbating COPD. Also, the presence of an adequate caregiver was considered mandatory. Such expert opinions may be clinically useful and may be considered when treatment-specific fitness criteria are updated to include Venetoclax/HMA. [ABSTRACT FROM AUTHOR]

5-Azacytidine is an effective therapy in high risk MDS and oligoblastic AML. This “real life” analysis was made on 185 patients treated with 5-azacytidine in 10 centers afferent to REL (“Rete Ematologica Lombarda”), a network in Lombardia region. The aim was to assess the influence of disease and comorbidity risk assessments on the survival. The results confirm the utility of 5-azacitidine in prolonging OS regardless of advanced age and the presence of comorbidities. They also encourage an early treatment since patients with IPSS-R High risk MDS have better outcome with respect to Very High risk ones. According to the IPSS cytogenetic risk, there was no difference in the outcome between Intermediate and High risk patients. Nevertheless, a poorer cytogenetic risk, according to the IPSS-R cytogenetic stratification, negatively influenced the outcome. [ABSTRACT FROM AUTHOR]