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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.

Introduction: Coronavirus disease 2019 (COVID-19) vaccines are considered to be safe. Only few cases of vaccine-induced immune thrombocytopenia or immune hemolysis have been reported so far. Evans syndrome (ES) is a very rare syndrome characterized mainly by warm autoimmune hemolytic anemia (wAIHA) and immune thrombocytopenia (ITP). Case presentation: We present a case of a 47‐year‐old male with a history of wAIHA, diagnosed in 1995 and successfully treated with glucocorticoids, with sustained remission. ITP was diagnosed in May 2016. Due to refractoriness to glucocorticoids, intravenous immunoglobulins (IVIGs), azathioprine and vinblastine, he was splenectomised in April 2017, resulting in complete remission. In May 2021, eight days after the second dose of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine, he experienced mucocutaneous bleeding. Blood tests showed platelet count (PC) of 8×109/L, while his hemoglobin (Hb) was normal (153 g/L). He was treated with prednisone and azathioprine, without response. On day 28 after vaccine administration, weakness, jaundice and dark brown urine occurred. His laboratory tests: PC 27×109/L, Hb 45 g/L, reticulocytes 10.4%, total bilirubin 106.6 μmol/L, direct bilirubin 19.8 μmol/L, lactate dehydrogenase 633 U/L, haptoglobin ˂0.08 g/L, and positive Coombs test were consistent with ES relapse. After treatment with glucocorticoids, azathioprine and IVIGs, his blood count finally improved (PC 490×109/L, Hb 109 g/L) and remained stable on day 40 of hospitalization. Conclusions: Although it is unclear whether the relationship between COVID-19 vaccination and relapse of ES in our patient is coincidental or causal, it highlights the need for monitoring of serious outcomes following vaccination.

Background and Objectives: Hyperleukocytosis in acute myeloid leukemia (AML) is life-threatening, often complicated by leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulation (DIC), with very high early mortality. Leukapheresis (LA) can rapidly reduce circulating blast burden, but its effect on survival and prognostic relevance of disease markers remains unclear. Materials and Methods: We retrospectively analyzed 74 adult AML patients with WBC > 100 × 109/L treated at the University Clinical Center of Serbia between 2014 and 2024: 28 received LA plus cytoreduction (LA group), and 46 received cytoreduction alone (non-LA group). We evaluated 15-, 30-, and 90-day mortality and overall survival (OS), and assessed clinical, laboratory, and immunophenotypic predictors using Cox regression, with separate subgroup analyses. Results: Patients in the LA group had significantly higher baseline leukocyte counts and LDH (p = 0.18 and p = 0.024, respectively). Although LA resulted in a median 34% reduction in WBC, there was no statistically significant difference in early mortality: 15-day survival was 68% vs. 76% (HR 0.70, p = 0.423), 30-day survival 50% vs. 65% (HR 0.62, p = 0.197), and 90-day survival 39.3% vs. 41.3% (HR 0.85, p = 0.604). Median OS was similarly poor, about 1 month in the LA group compared to 2 months in the non-LA (HR 0.73). Across all patients, ECOG PS ≥2, elevated LDH, TLS, and DIC were the strongest indicators of early death. In the LA group, elevated LDH and increased peripheral blood (PB) monocyte count predicted 15-day mortality (p = 0.021 and p = 0.031, respectively), but lost significance by day 90. In non-LA patients, CD25 positivity (p = 0.034) and DIC (p = 0.045) predicted 15-day death. By day 90, CD25 expression (p = 0.048) remained prognostic, while PB blast percentage (p = 0.045) and PB monocyte count (p = 0.017) emerged as additional adverse prognostic predictors in the non-LA group. In multivariate analysis, higher PB blast percentage, CD25 positivity, and ECOG PS ≥ 2 independently predicted poorer OS. Conclusions: Although LA did not reduce early mortality in the entire cohort, the loss of prognostic significance of elevated LDH, high PB blast percentage, PB monocyte burden, and CD25 expression in the LA group may suggest that the intervention can attenuate the impact of biologically aggressive disease.

Autoimmune hemolytic anemia (AIHA) is a rare, very heterogeneous, and sometimes life-threatening acquired hematologic disease characterized by increased red blood cell (RBC) destruction by autoantibodies (autoAbs), either with or without complement involvement. Recent studies have shown that the involvement of T- and B-cell dysregulation and an imbalance of T-helper 2 (Th2) and Th17 phenotypes play major roles in the pathogenesis of AIHA. AIHA can be primary (idiopathic) but is more often secondary, triggered by infections or drug use or as a part of other diseases. As the location of origin of autoAbs and the location of autoAb-mediated RBC clearance, as well as the location of extramedullary hematopoiesis, the spleen is crucially involved in all the steps of AIHA pathobiology. Splenectomy, which was the established second-line therapeutic option in corticosteroid-resistant AIHA patients for decades, has become less common due to increasing knowledge of immunopathogenesis and the introduction of targeted therapy. This article provides a comprehensive overview of current knowledge regarding the place of the spleen in the immunological background of AIHA and the rapidly growing spectrum of novel therapeutic approaches. Furthermore, this review emphasizes the still-existing expediency of laparoscopic splenectomy with appropriate perioperative thromboprophylaxis and the prevention of infection as a safe and reliable therapeutic option in the context of the limited availability of rituximab and other novel therapies.

Background and Objectives: The revised international prognostic scoring system (IPSS-R) remains the most widely used prognostic tool for myelodysplastic syndrome (MDS). There is growing evidence that inflammation and immunological dysregulation are important in the pathogenesis of MDS. Moreover, monocytopenia and lymphocytopenia are correlated with adverse outcomes in patients with MDS. However, standard guideline-driven diagnostic and prognostic models do not evaluate host immunity parameters. This study explored the prognostic relevance of monocytopenia and lymphocytopenia at diagnosis for overall survival (OS) as medical endpoints independent of IPSS-R. Materials and Methods: This retrospective study included 217 patients with MDS diagnosed and treated at the University Clinical Center of Serbia between July 2019 and July 2024. MDS was diagnosed based on the 2016 World Health Organization (WHO) criteria. Results: Univariate analysis revealed that patients with monocytopenia (absolute monocyte count (AMC) < 0.3 × 109/L) had adverse outcomes compared to individuals with normal AMC (AMC ≥ 0.3 × 109/L) (median OS with/without risk factor 20 months vs. 60 months, respectively, log rank test p = 0.0009). Moreover, lymphocytopenia (absolute lymphocyte count (ALC) < 1.2 × 109/L) was shown to have a significant impact on survival (median OS with/without risk factor 17 months vs. 29 months, respectively; log-rank p = 0.0182). In further multivariate analysis, IPSS-R, AMC < 0.3 × 109/L, ALC < 1.2 × 109/L, and DMAs/HSCT were identified as independent prognostic factors for OS (Cox multivariate model, p < 0.001, p = 0.0237, p = 0.006, p < 0.001, respectively). Conclusions: Our findings suggest that ALC and AMC can serve as readily accessible and verifiable prognostic tools in MDS at presentation. Combined with IPSS-R, these markers may provide additional prognostic insights, enabling better risk stratification in MDS patients who could benefit from future immunotherapies.

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.

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.

Deregulation of the apoptotic process underlies the pathogenesis of many cancers, including leukemia, but is also very important for the success of chemotherapy treatment. Therefore, the gene expression profile of main apoptotic factors, such as anti-apoptotic (B-cell lymphoma protein 2) and pro-apoptotic (BCL2-associated X), as well as genes involved in the multi-drug resistance ( ), could have significant impact on the prognosis and could be used as targets for specific therapy. We analyzed the expression of , and in bone-marrow samples collected at diagnosis from 51 adult patients with acute myeloid leukemia with normal karyotype (AML-NK) using real-time polymerase chain reaction method, and examined their prognostic potential. Increased expression of ( ) was associated with the presence of chemoresistance (p = 0.024), while patients with low expression were more prone to relapse (p = 0.047). Analysis of the combined effect of and expression showed that 87% of patients with status were resistant to therapy (p = 0.044). High expression of was associated with status (p < 0.001), and with absence mutations (p = 0.019). The present analysis of , and gene expression profiles is the first study focusing solely on AML-NK patients. Preliminary results showed that patients with high expression are likely to experience resistance to chemotherapy, and may benefit from specific anti-BCL2 treatment. Further investigations conducted on a larger number of patients could elucidate actual prognostic significance of these genes in AML-NK patients.

Acute myeloid leukemia (AML) is a heterogeneous malignant disease both on clinical and genetic levels. AML has poor prognosis and, therefore, there is a constant need to find new prognostic markers, as well as markers that can be used as targets for innovative therapeutics. Recently, the search for new biomarkers has turned researchers’ attention towards non-coding RNAs, especially long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). We investigated the expression level of growth arrest-specific transcript 5 (GAS5) lncRNA in 94 younger AML patients, and also the expression level of miR-222 in a cohort of 39 AML patients with normal karyotype (AML-NK), in order to examine their prognostic potential. Our results showed that GAS5 expression level in AML patients was lower compared to healthy controls. Lower GAS5 expression on diagnosis was related to an adverse prognosis. In the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic effect of GAS5low/miR-222high status on disease prognosis was not established. This is the first study focused on examining the GAS5 and miR-222 expression pattern in AML patients. Its initial findings indicate the need for further investigation of these two non-coding RNAs, their potential roles in leukemogenesis, and the prognosis of AML patients.

Background: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. Aim: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. Methods: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. Results: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23–6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581–63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329–13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212–23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948–21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092–5.007). Conclusions: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30.