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Background and Objectives: With the advent of novel therapies for nucleophosmin gene (NPM1)-mutated acute myeloid leukemia (AML), there is a growing need for the reliable prediction of NPM1 mutations. This study explored the role of cytomorphological features in the early prediction of NPM1-mutated AML. Materials and Methods: Altogether, 212 de novo AML cases with normal karyotypes, diagnosed and treated at a single institution within 5 years (2018–2023), were retrospectively evaluated. A final diagnosis of NPM1-mutated AML, based on the World Health Organization (WHO) integrated criteria, including real-time based identification of NPM1 mutation and normal karyotype, was established in 83/212 (39.15%) cases. Results: Cup-like blasts (CLBs), a cytomorphological feature suggestive of NPM1-mutated AML, were detected in 56/83 (67%) patients. Most cases (44/56, 78.6%) had CLB ≥ 10%. In total, 27 of 83 AML NPM1-mutated patients had no CLB morphology (missed call). Additionally, two of 212 had CLB morphology without confirmed NPM1 mutation (wrong call). The positive/negative predictive values of cytomorphological evaluation for CLB ≥ 10% were 95.7%/75.6%, with sensitivity/specificity of 53%/98.5%, while the accuracy was 80.7%. We noted an increased percentage of CLBs (≥15%) in 77.8% and 50% of patients with AML without and with granulocytic maturation, respectively (the specificity for NPM1 mutation prediction was 100%). CLB was associated with fms-like tyrosine kinase 3 (FLT3) mutation (p = 0.03), but, without statistical significance for CLB ≥ 10% and CLB ≥ 15%. Conclusions: Our investigation confirmed that the morphological identification of CLB at diagnosis represents a reliable and easily reproducible tool for the early prediction of NPM1 mutations, enabling a streamlined genetic work-up for its confirmation. This may facilitate considering the early administration of individualized therapies by clinicians for specific patients.

Background Patients with acute myeloid leukemia (AML) are at increased risk of venous thromboembolic events (VTE). However, thromboprophylaxis is largely underused. Objectives This study aimed to determine possible VTE development risk factors and to develop a novel predictive model. Methods We conducted a retrospective cohort study of adult patients with newly diagnosed AML. We used univariate and multivariable logistic regression to estimate binary outcomes and identify potential predictors. Based on our final model, a dynamic nomogram was constructed with the goal of facilitating VTE probability calculation. Results Out of 626 eligible patients with AML, 72 (11.5%) developed VTE during 6 months of follow-up. Six parameters were independent predictors: male sex (odds ratio [OR] 1.82, 95% confidence interval [CI]: 1.077–2.065), prior history of thrombotic events (OR 2.27, 95% CI: 1.4–4.96), international normalized ratio (OR 0.21, 95% CI: 0.05–0.95), Eastern Cooperative Oncology Group performance status (OR 0.71, 95% CI: 0.53–0.94), and intensive therapy (OR 2.05, 95% CI: 1.07–3.91). The C statistics for the model was 0.68. The model was adequately calibrated and internally validated. The decision-curve analysis suggested the use of thromboprophylaxis in patients with VTE risks between 8 and 20%. Conclusion We developed a novel and convenient tool that may assist clinicians in identifying patients whose VTE risk is high enough to warrant thromboprophylaxis. Essentials Acute myeloid leukemia patients are at increased risk of venous thromboembolism (VTE). Predictive model for VTE development in acute myeloid leukemia patients was created. Six parameters were included in the model: male sex, prior history of thrombotic events, international normalized ratio (iNR), Eastern Cooperative Oncology Group performance status and intensive therapy approach. This model could identify patients whose VTE risk is high enough to warrant thromboprophylaxis.

The treatment of chronic lymphocytic leukemia (CLL) consists of the continuous use of Bruton tyrosine kinase inhibitors (BTKis) such as ibrutinib, acalabrutinib, zanubrutinib and pirtobrutinib, or Bcl-2 inhibitors, such as venetoclax. Overall survival (OS) and progression-free survival (PFS) of CLL patients are significantly improved with the use of these therapies. Adverse effects (AEs) that can occur during treatment and the presence of pre-existing comorbidities in patients can influence subsequent treatment outcomes and, consequently, OS and PFS. Managing these AEs, including cardiologic toxicity and infections (including fungal infections), as well as treating cardiovascular and other comorbidities, can be challenging due to potential drug interactions with the medications used for the management of AEs and comorbidities. Therefore, this review examined the key challenges associated with the concomitant use of novel CLL therapies and medications for managing comorbidities and AEs. This review aims to enhance and facilitate the management of patients with CLL.

The predictors of intestinal carriage of vancomycin-resistant Enterococcus spp. (VRE) among high-risk patients in the counties of the Southeast Europe Region are insufficiently investigated, yet they could be of key importance in infection control. The aim of the study was to identify risk factors associated with fecal VRE colonization among high-risk inpatients in university hospitals in Serbia. The study comprised 268 inpatients from three university hospitals. Data on patient demographics and clinical characteristics, length of hospital stay, therapy, and procedures were obtained from medical records. Chi-squared tests and univariate and multivariate logistic regressions were performed. Compared to the hemodialysis departments, stay in the geriatric departments, ICUs, and haemato-oncology departments increased the risk for VRE colonization 7.6, 5.4, and 5.5 times, respectively. Compared to inpatients who were hospitalized 48 h before stool sampling for VRE isolation, inpatients hospitalized 3–7, 8–15, and longer than 16 days before sampling had 5.0-, 4.7-, and 6.6-fold higher risk for VRE colonization, respectively. The use of cephalosporins and fluoroquinolones increased the risk for VRE colonization by 2.2 and 1.9 times, respectively. The age ≥ 65 years increased the risk for VRE colonization 2.3 times. In comparison to the University Clinical Centre of Serbia, the hospital stays at Zemun and Zvezdara University Medical Centres were identified as a protector factors. The obtained results could be valuable in predicting the fecal VRE colonization status at patient admission and consequent implementation of infection control measures targeting at-risk inpatients where VRE screening is not routinely performed.

Introduction Hemorrhagic early death (HED) remains a major cause of treatment failure among patients with acute promyelocytic leukemia (APL). We aimed to investigate the prognostic potential of rotational thromboelastometry (ROTEM) for bleeding in patients with APL. Materials and Methods 31 newly-diagnosed APL patients (median age of 40 years; 14 female/17 male) that underwent treatment at the Clinic of Hematology UCCS from 2016-2020 with all-trans retinoic acid and anthracyclines were recruited. CBCs (complete blood count), conventional coagulation tests (CCTs), and ROTEM parameters obtained before treatment initiation were evaluated. Results All patients demonstrated at least one ROTEM parameter out of the reference range. ROTEM parameters associated with significant hemorrhage were EXTEM clotting time (CT) (P = 0.041) and INTEM amplitude 10 (A10) (P = 0.039), however, only EXTEM CT (P = 0.036) was associated with HED. Among CBCs and CCTs, only platelets were associated with significant bleeding (P = 0.015), while D-dimer was associated with both bleeding and HED (P = 0.001 and P = 0.002, respectively). Conclusion Our results indicate that ROTEM parameters may reveal hypocoagulability in APL patients and have the potential to improve current hemorrhage prognostic methods. Additionally, these results suggest the combination of ROTEM and CCTs might be useful in identifying patients at risk for HED.

One of the major findings of traditional investigations of speech errors is that a single segment is the smallest unit affected by speech errors, although the possibility that units smaller than the segment could play a role in explaining speech errors was not entirely rejected. A number of relatively recent studies using instrumental kinematic techniques for speech analysis bring evidence that errors often occur at subsegmental units of speech production, i.e. at the level of articulatory gestures. Such errors occur due to the coproduction of articulatory gestures, whereby the gestures from both the target consonant and the competing speech sound overlap. As they represent the gradient shift from one segment to another, they are often called gradient errors. Such processes are almost impossible to capture without the use of instrumental kinematic techniques, such as electropalatography (EPG). There are no instrumental kinematic studies of speech errors in Croatian speech. Thus, the aim of this paper is to use EPG to investigate speech errors produced in one Croatian tongue twister. The analysis was focused on /r/ and /l/ targets produced by 10 native female speakers of Croatian, while producing the tongue twister which facilitated speech errors in these two sounds. Each token of the target consonant was classified in one of the four categories: (1) perceptually and articulatorily correct production (P1A1); (2) articulatorily correct but perceptually incorrect production (P0A1); (3) perceptually correct but articulatorily incorrect production (P1A0) and (4) perceptually and articulatorily incorrect production (P0A0). The classification was made by the authors via auditory analysis and visual inspection of spectrograms and electropalatograms prior to the quantitative kinematic analysis. Subsequent analyses showed evidence of gradient errors, which would not be detected without the use of instrumental kinematic techniques. This investigation supports the claim that traditional method of collecting speech errors by perceptual analysis only is not sensitive enough to detect the subtleties of erroneous productions and speech motor control.

Patients with coronavirus disease 19 (COVID-19) have increased susceptibility to secondary respiratory infections including invasive pulmonary aspergillosis (IPA). COVID-19-associated pulmonary aspergillosis (CAPA) is difficult to diagnose and can be associated with increased mortality especially in severe immunodeficiency such as hematological malignancies. Our study evaluates IPA in COVID-19 patients defined as COVID-19-CAPA among patients with acute leukemia (AL). A retrospective single-center study analyzed 46 patients with COVID-19 infection and acute leukemia, admitted to the Clinic for Haematology, Clinical Center of Serbia, Belgrade between the 2 April 2020 and 15 May 2021. During hospitalization, all participants were diagnosed with probable IPA according to the previous consensus definitions. Positive serology and galactomannan (GM) detection values in bronchoalveolar lavage (BAL) and serum were used as microbiological criteria. COVID-19 associated probable IPA was found in 22% (9/41) tested patients, where serum GM and IgM anti-Aspergillus antibodies were positive in 12% (5/41) and 10% (4/41) had positive serology for aspergillosis. One patient died while eight recovered during follow-up. Our study showed that COVID-19 might be a risk factor for IPA development in patients with AL. Early diagnosis and prompt treatment are required as reported mortality rates are high.

Mutations in the isocitrate dehydrogenase 1 and 2 ( and ) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. In our study samples from 110 adult AML-NK were studied for the presence of and mutations, their associations with other prognostic markers and disease outcome. We also analyzed the stability of these mutations during the course of the disease in complete remission (CR) and relapse. mutations were found in 25 (23%) patients. + patients tend to have lower CR rate compared to -patients (44% 62.2%, p = 0.152), and had slightly lower disease free survival (12 months 17 months; p = 0.091). On the other hand, the presence of mutations had significant impact on overall survival (2 7 months; p = 0.039). The stability of mutations were studied sequentially in 19 + patients. All of them lost the mutation in CR, and the same mutations were detected in relapsed samples. Our study shows that the presence of mutations confer an adverse effect in AML-NK patients, which in combination with other molecular markers can lead to an improved risk stratification and better treatment. Also, mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection.

Introduction: The treatment of acute myeloid leukemia (AML) is accompanied by infectious complications, particularly during induction. The surge of multi-drug resistant (MDR) bacteria represents an additional problem for the health care of patients with AML. Methodology: A retrospective analysis of infectious complications was performed in 84 patients with AML undergoing induction therapy hospitalized between October 2020 and April 2023 at the Clinic of Hematology, University Clinical Centre of Serbia. Results: From 84 patients and 95 bacterial isolates, Enterococcus spp. was the most frequent Gram-positive bacterium (26%), showing a 56% resistance rate to vancomycin, and a 77.3% resistance rate to carbapenems, with a 4.3% resistance rate to linezolid and no resistance to tigecycline detected. The most common Gram-negative bacterium, Klebsiella spp. (28%), was resistant to cephalosporins, carbapenems, fluoroquinolones (88%, 84.6%, and 88.5% respectively), with a sizeable resistance rate to ceftazidime/avibactam and colistin (20% and 36.4% respectively). XDR Klebsiella spp. dominated the isolated strains, being detected in 57.7% of cultures, whereas Enterococcus spp. was identified as MDR or XDR in 40% and 28% respectively. The factors associated with developing MDR infections were ECOG PS > 2 (p = 0.024), sepsis (p = 0.0016), and the presence of two or more infectious syndromes (p = 0.016). Patients with a confirmed MDR bacterial infection had a mortality rate of 36.7%. Conclusions: Our work demonstrates that the frequency of infections in this population is high, especially with MDR and XDR strains of Klebsiella spp. and Enterococcus spp., which are accompanied by high rates of early death.

Immune reconstitution (IR) after allogeneic stem cell transplantation has been highlighted as pivotal in achieving favorable long-term outcomes by influencing the rates of infection, graft versus host disease (GvHD) and relapse. However, data on the impact of different lymphocyte subsets influencing outcomes is conflicting. Furthermore, the importance of immune reconstitution parameters in patients previously not experiencing major post-transplant complications is lacking. We evaluated the clinical impact of day 90 NK cell, CD4 T-cell, CD8 T-cell, B-cell, and NKT cell counts on transplant outcomes by performing a landmark analysis in event-free patients. Lymphocyte subset counts were obtained from 70 patients undergoing in vivo T-cell depleted allogeneic transplantation from 2018 to 2024. Patients eligible for the study experienced no acute GvHD, poor graft function, graft failure, or relapse in the first three months after transplantation-prior to obtaining IR data. We associated lymphocyte subset counts to overall survival (OS), non-relapse mortality (NRM), cumulative incidence of relapse (RI), and secondary graft failure/poor graft function. High NK cell counts on day 90 (>178/μL) were associated with improved OS (P=0.039) and lower rates of NRM (1-year cumulative incidence of 5.7% versus 31.4%, HR 0.16, 95% CI 0.04-0.69, P=0.014). A protective effect on RI was not found. We found no patient, disease or transplant-related variables to be significantly associated with day 90 NK cell counts. The results suggest that high NK cell counts on day 90 after T-cell depleted allogeneic transplantation independently protect from NRM and improve OS in patients without prior major post-transplant complications.