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.

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.

Background: Acute promyelocytic leukemia (APL) is frequently associated with disseminated intravascular coagulation (DIC), leading to potentially life-threatening bleeding. Compared to bleeding, thromboses are a less commonly encountered problem. Objective: The objective of our study was to identify the incidence and predictive value of demographic data, clinical–laboratory parameters, and thrombosis risk assessment models (RAMs) for venous thromboembolism (VTE) in patients with APL. Methods: This study was a retrospective study conducted on adult patients with APL who were treated between 2006 and 2024 at the Clinic of Hematology UCCS with all-trans retinoic acid (ATRA) and anthracycline. The demographic and clinical–laboratory data related to VTE were collected and analyzed alongside the predictive value of two RAMs proposed by Al-Ani and Paterno and colleagues. Results: Among the one-hundred-fifty-five adult patients with APL, VTE was diagnosed in twenty-eight cases (18.1%). The most common location for thrombosis was in the central venous catheter (CVC), which affected twelve (42.8%) patients. A total of six (21.4%) patients had deep vein thrombosis (DVT), one patient (3.6%) showed a pulmonary embolism (PE), and thrombosis at unusual sites was present in nine (32.1%) patients. Our analyses showed that neither Al-Ani’s RAM nor the RAM proposed by Paterno and colleagues were predictive for VTE in patients with APL. The C statistics value for the Al-Ani model was ROC = 0.514, and, for Paterno’s RAM, it was ROC = 0.521. The independent risk factors for VTE, identified via multivariate analysis, were CD114 expression (p = 0.005, OR = 6.4 IC 95%: [1.8–23.2]) and the absence of bleeding at presentation (p = 0.013, OR = 0.086 IC 95%: [0.01–0.59]). Conclusions: To the best of our knowledge, this is the first study showing that a higher expression of CD114 increases the risk of VTE. The absence of bleeding at presentation in patients with APL correlates with thrombosis. Further analyses are needed to confirm these findings and help to develop therapeutic strategies to prevent VTE complications. So far, no risk assessment model has been sufficient to stratify patients with APL according to their risk of VTE.

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.

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.

Introduction: The introduction of all-trans retinoic acid (ATRA) has transformed acute promylocitic leucaemia (APL) from a highly fatal to a curable disease. However, significant frequency of early death (ED) and relapse represent challenges in everyday practice. The aims of this study are to report our 20 years long experience using AIDA-based protocols and to assess the predictive value of clinical and laboratory parameters for ED/relapse development. Material and methods: This retrospective study included patients treated at the Clinic for Hematology, UKCS in the period 2004-2024. RS was defined as death within the first 30 days of hospitalization. Results: 158 patients were included. ED and relapse occurred in 38/158 (24%) and 15/119 (12.6%) patients. ED rate stayed stable through time (2004-2008 period 20.6%, 2009-2013 21.9%, 2014-2018 23.1%, 2019-2024 27%) with bleeding as the most frequent cause (42%), followed by DS (24%) and infection (16%). Final predictors for ED development were ISTH DIC score (p=0.008, OR 2.38, 95% CI 1.25-4.53), aPTT (p=0.009, OR 0.79, 95% CI 0.66-0.94), ECOG PS (p<0.001, OR 2.96, 95% CI 1.63-5.39). Predictors for relapse were: ECOG PS ≥ 3 (21.7% vs 78.3%, p=0.019) and bcr3 PML-RARA transcript (29.6% vs 70.4%, p=0.046). Conclusion: Our experience showed a very high rate of ED, with haemorrhage, DS and infection as a main reason. Preventive strategies should include comprehensive medical education, regarding prompt recognition, appropriate early transfusion support therapy, and the rapid initiation of ATRA. Patients with high ECOG PS and ISTH DIC score probably need different coagulation monitoring and reinvented therapy.