Search Results (4)

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. Full article

Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine presents variable pharmacokinetics affected by numerous parameters, leading to significant inter- and intra-individual variation. Therefore, therapeutic drug monitoring of plasma clozapine levels confers a significant benefit in everyday clinical practice by increasing the confidence of the prescribing doctor to the drug and the adherence of the patient to the treatment, mainly by ensuring effective treatment and limited dose-related side effects. In the present systematic review, we aimed at identifying how a full range of adverse effects relates to plasma clozapine levels, using the Jadad grading system for assessing the quality of the available clinical evidence. Our findings indicate that EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation correlate to plasma clozapine levels, whereas QTc, myocarditis, sudden death, leucopenia, neutropenia, sialorrhea, are rather unrelated. Rapid dose escalation at the initiation of treatment might contribute to the emergence of myocarditis, or leucopenia. Strategies for managing adverse effects are different in these conditions and are discussed accordingly. Full article

Since myeloproliferative neoplasms (MPN) pose a significant risk for vascular and thrombotic complications, cytoreductive therapies, such as hydroxyurea (HU), interferon (IFN) inhibitors, and Janus kinase (JAK) inhibitors are recommended for patients at high risk. However, these agents also place patients at increased risk for drug-related cutaneous adverse events. Herein, we review the literature on skin toxicity related to the use of drugs for the treatment of MPN. Overall, the cytoreductive agents used for MPN are generally well tolerated and considered to be safe, except IFN, for which dropout rates as high as 25% have been reported. While IFN is known to give rise to flu syndrome, it rarely leads to hematological alterations. The most common hematological side effects of HU are mild and include granulocytopenia, anemia, and thrombocytopenia. The JAK inhibitor ruxolitinib has been associated with cytopenia and a higher incidence of viral infections, as well as increased risk for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Based on the present analysis, it can be concluded that cutaneous toxicity is not a negligible complication of commonly used treatments for MPN. While further research is needed, patients on these agents, and especially those with a history of cutaneous malignancies, should undergo thorough skin examination before and during therapy. In addition, detailed history is critical since many patients who develop non-melanoma skin cancer have multiple preexisting risk factors for cutaneous carcinogenesis. Full article

The aim of this study was to present the diagnostic problems in pts treated for invasive aspergillosis (IA) in the Illrd Clinic of the Institute of Tuberculosis in the years 1993–2005. The material consisted of clinical documentation of 18 pts. 15 out of 18 pts (83.4%) died. In all those cases autopsy examination was done. In 13 pts IA was the main and in another 2 only the accessory cause of death. AU pts were treated with corticosteroids and/or cytostatic drugs because of lung cancer (13 pts), haematologic disorders (1 pts), Wegener's granulomatosis (3 pts) and idiopathic pulmonary fibrosis (1 pts). In 13 out of 18 pts granulocytopenia was revealed (on an average from 0.008 × 109/L to 0.95 × 109/L) one month before death. In 13 pts IA was limited to the lungs, in 5 others there were also fungal lesions in brain, kidneys, liver, spleen, pleura, pericardium and heart. Pts with disseminated fonn ofIA had significantly lower granulocyte count and were treated with higher doses of corticosteroids than others. Immunosupressive drugs and granulocytopenia can be regarded as predisposing factors. IA was diagnosed before death only in 5 out of 18 pts. This was mainly caused by the lack of the symptoms of in­fection (4 pts) and negative results ofmycological (6 pts) and serological examination (8 pts). We should underline that mycological examination was only done in 11 pts and serological examination of blood for fungal antigen only in 6 pts. We conclude that mycological infection ought to be searched in all pts treated with high doses of corticosteroids and those with prolonged granulocytopenia, especially if they have the symptoms of infection which does not respond to antibiotic therapy. Full article