Objective: To investigate the association between baseline platelet count at diagnosis and complete remission (CR) rate, severe bleeding, and overall survival (OS) in newly diagnosed acute myeloid leukemia (AML). Methods: This single-center retrospective cohort study enrolled 356 non-acute promyelocytic leukemia (non-APL) AML patients treated with first-line therapy between January 2020 and December 2025. Patients were classified as having a low baseline platelet count (<50 × 10⁹/L, n=218) or a normal/high count (≥50 × 10⁹/L, n=138). The primary outcomes were severe bleeding (CTCAE grade ≥3) and overall survival administratively censored at 24 months. Parsimonious multivariable Logistic and Cox models, Kaplan–Meier analysis, 1:1 propensity score matching (PSM), continuous platelet modeling, restricted cubic splines (RCS), and alternative-threshold analyses were used. Results: CR (53.7% vs. 50.7%, P=0.665) and CR/CRi rates (63.3% vs. 68.8%, P=0.339) did not differ significantly between groups. Severe bleeding was more frequent in the low-platelet group (22.5% vs. 8.7%, P=0.001), and low baseline platelet count remained associated with severe bleeding after parsimonious adjustment (OR=3.124, 95% CI 1.447–6.746, P=0.004). Kaplan–Meier analysis showed lower 24-month OS in the low-platelet group (58.2% vs. 77.8%; log-rank P<0.001), and the adjusted 24-month Cox model yielded an HR of 1.843 (95% CI 1.167–2.910, P=0.009). Per 10 × 10⁹/L higher baseline platelet count, the adjusted odds of severe bleeding were 24.2% lower and the 24-month death hazard was 11.4% lower. RCS analyses found no statistically significant departure from linearity. In the PSM sensitivity analysis, which retained residual covariate imbalance, the 24-month OS estimate remained significant (HR=1.981, 95% CI 1.228–3.193, P=0.005), whereas the severe-bleeding association was not confirmed (OR=2.286, 95% CI 0.940–5.556, P=0.068). Conclusion: A baseline platelet count <50 × 10⁹/L was associated with severe bleeding and lower 24-month OS, but not with induction CR, in this retrospective AML cohort. This study did not assess incremental predictive value beyond established AML risk systems; the findings should therefore be considered hypothesis-generating and require prospective external validation.
Abstract. Background: During the last few decades, screening for dysglycemia in transfusion-dependent β-thalassemia patients (β-TDT) with an oral glucose tolerance test (OGTT) using fasting (FPG) and 2-hour plasma glucose (2h-PG) samples has been recommended at 10, 12, 14, and 16 years and annually thereafter. A precise measurement of blood glucose (BG) concentration is the mainstay for an accurate diagnosis of dysglycemia, in order to limit the risk of false-positive (i.e., overdiagnosis) and false-negative (i.e., underdiagnosis) results, especially in patients with BG values near the cut-off values. Research objective: The primary objective of our survey was to describe the procedures followed during the pre-analytical phase of screening for dysglycemia, based on the actual clinical practice of Centers following β-TDT patients. Answers from the survey were compared with international recommendations (American Diabetes Association and World Health Organization). Methods: This observational study was based on an online questionnaire survey. All members of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) were officially invited. The questionnaire consisted of 6 sections and 22 questions, including single-choice, multiple-choice, and open-ended descriptive answers. Results: 14 out of 18 invited Centers [Bulgaria, Cyprus, Greece, Iran (2), Italy (2), Oman, Qatar, Sri Lanka, Türkiye (3) and United Kingdom] accepted and completed the survey promoted by the ICET-A with a response rate of 77.7 % The total number of β-TDT patients followed in the participating Centers was 3,372 and 2,932 (86.9 %) were over the age of 10 years. The total number of thalassemia related diabetes mellitus (Th-RDM) reported by all Centers was 549. The total mean prevalence of Th-RDM was 14.7 ± 10.2 % . Generally, the survey has shown that there was a variable adherence to, and deviations from, current international guidelines. The lowest adherence rate regarded the information and instructions given to patients prior to OGTT (~56%), and how the BG samples were stored from the time of collection to time of centrifugation and analysis (~80 %). Differences in these factors may result in unintended variations in the prevalence of dysglycemia and have important implications for clinical practice. Conclusions: Many factors across the total testing process (sample collection, storage and transport during the preanalytical phase) can significantly impact OGTT accuracy and reproducibility, especially in patients with blood glucose values closer to the cut-off values. To minimize pre-analytical errors, a more precise diagnostic approach associated with closer patient follow-up is needed to reduce the risk of errors in glucose measurement.
Background. Screening for dysglycemia with an annual oral glucose tolerance test (OGTT) is recommended in transfusion-dependent β-thalassemia (β-TDT), but adherence in routine practice is low. Fasting surrogate indices of β-cell function and insulin sensitivity could offer a less burdensome alternative. Aims. To evaluate in adult β-TDT patients with normal fasting plasma glucose (FPG < 100 mg/dL): (i) the performance of fasting HOMA-2 indices (HOMA2-IR, HOMA2-%β, HOMA2-%S) and their disposition index as predictors of dysglycemia, and (ii) the comparative value of basal versus dynamic OGTT-derived markers (30-min and 1-h plasma glucose, insulinogenic index [IGI], IGI × ISI Matsuda index and IGI/HOMA2-IR), as predictors of hyperglycemia. Methods. A single-centre retrospective analysis of 42 β-TDT patients (19 males / 23 females; mean age 29.2 ± 5.9 yr) with FPG < 100 mg/dL who underwent a standard 75-g 2-h OGTT between January 2011 and September 2025. Patients were classified as those with normal glucose tolerance (NGT; n = 19) or those with impaired glucose tolerance (IGT: n= 20) or thalassemia-related diabetes mellitus (Th-RDM: n = 3). Fasting and dynamic indices were compared by ANOVA and Mann–Whitney U; associations were tested by Pearson/Spearman correlation and by three sequential multivariable linear regression models with 2-h plasma glucose as the dependent variable. ROC analysis with Youden's index identified optimal cut-offs. Results. Fasting HOMA2-IR, HOMA2-%β and HOMA2-%S did not differ significantly between NGT and hyperglycemic patients and were not independent predictors of 2-h plasma glucose. In contrast, in the total group, 30-min PG, 1-h PG, IGI, IGI × ISI Matsuda index and IGI/HOMA2-IR all differed significantly between groups (p: ≤ 0.0082) and were inversely correlated with 2-h PG. Receiver operating characteristic (ROC) analysis and area under the curve (AUC-ROC) were used to assess diagnostic performance of the most significant variables The ROC-AUC cut-offs for predicting dysglycemia were 122.5 mg/dL for 30-min PG (sensitivity 0.91, specificity 0.52), 134 mg/dL for 1-h PG (0.95, 0.10), 5.7 for IGI × ISI Matsuda index (0.87, 0.47) and 1.33 for IGI/HOMA2-IR (0.87, 0.57). Conclusions. Fasting HOMA-2 indices alone are not reliable predictors of dysglycemia in β-TDT patients with PG < 100 mg/dL. The dynamic IGI/HOMA2-IR ratio and the 30-min/1-h post-load plasma glucose may be used to stratify patients at high risk of glucose dysregulation and could minimize reliance on the full annual OGTT. Larger, prospective multicentre studies are needed to validate these cut-offs.
A previously healthy 15-year-old girl from a VL-endemic rural area of north-western Greece presented with 15 days of high-grade fever, a two-month history of morning arthralgias, and recurrent macroscopic hematuria. Examination revealed malar rash, livedo reticularis, frontotemporal alopecia, hepatosplenomegaly, bilateral pleural and pericardial effusions, Coombs-positive anemia, leukopenia, nephrotic-range proteinuria, and hypocomplementemia. discontinued.
Penile abscess is an uncommon urological infection, and isolation of Salmonella enteritidis from a penile abscess is exceptionally rare. Chronic myeloid leukaemia (CML) is a clonal myeloproliferative neoplasm driven by the BCR::ABL1 fusion gene. Most patients are diagnosed in chronic phase, and chronic-phase CML before intensive chemotherapy or progression to accelerated or blast phase should not be overinterpreted as a strong immunosuppressive condition predisposing directly to invasive bacterial infection. We report a microbiologically confirmed S. enteritidis penile abscess in an adolescent with newly diagnosed chronic-phase CML, most plausibly due to haematogenous seeding of locally inflamed or compromised genital tissue during bacteraemia.
Background: Critically ill patients in intensive care units (ICUs) are susceptible to cytomegalovirus (CMV) reactivation. Increased mortality, length of ICU stay, and duration of mechanical ventilation (MV) were associated with CMV in these patients. Methods: The patients who received antiviral therapy (ganciclovir) for CMV reactivation (n=39) were compared with patients without viremia (n=39). Results: The reactivation group had higher mortality rates (n=28, 71.8%) than the control group (n=15, 28.5%). Logistic regression analysis showed that length of ICU stay, the day of steroid treatment, duration of MV, alanine aminotransferase (ALT), and hemoglobin level were identified as independent predictors of CMV reactivation. The optimal cut-off value of ALT was found to be >58 IU/ml (p<0.001, AUC: 0.721, sensitivity: 56.41, specificity: 87.18), and hemoglobin was found to be ≤ 9.8 g/dL (p<0.001, AUC: 0.708, sensitivity: 56.41, specificity: 84.62). In patients who received antiviral therapy, the baseline DNA levels were higher in the non-survivor group (n=28), but no statistically significant difference was detected. A downward trend of viremia level was seen in both non-survivors and survivors (n=11) groups. Conclusions: Reactivation had an impact on mortality; despite antiviral therapy and polymerase chain reaction (PCR) monitoring, it was also associated with increased length of ICU stay, MV, and steroid treatment. Lower hemoglobin and increased ALT levels can be considered as guiding laboratory parameters in predicting CMV reactivation.
Systemic mastocytosis (SM) is a rare hematological neoplasm characterized by infiltration of tissue by clonal mast cells (MCs) and pleiotropic clinical presentation. When SM is clinically aggressive, patients necessitate treatment with tyrosine kinase inhibitors (TKIs). Response to therapy may be unsatisfactory, especially for younger patients, and the possibility of allogeneic transplant should be discussed.
Dear Editor, Carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) remains a major global health challenge, associated with high mortality and limited therapeutic options [1,2]. Although novel β-lactam/β-lactamase inhibitor combinations (BL/BLI), such as meropenem/vaborbactam (M/V), have improved treatment outcomes, M/V-resistance is increasingly reported, often due to porin alterations or overexpression of blaKPC genes [2,4,7]. Imipenem/cilastatin/relebactam (IMI/REL) represents an alternative strategy, combining a carbapenem with a potent class A/C β-lactamase inhibitor that can restore activity against certain carbapenemase-producing strains [3–6].Herein, we describe the first documented case of successful treatment of a polymicrobial bloodstream infection caused by M/V-resistant but IMI/REL-susceptible KPC-Kp, with concomitant Enterococcus faecalis, in an elderly, frail patient.
Cytokine release syndrome (CRS) following haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is common, but its prognostic significance remains unclear. We retrospectively analyzed 104 consecutive patients undergoing haplo-HSCT (2008–2024); after excluding early infections, 86 patients were evaluable. CRS was defined according to ASTCT criteria. The primary endpoint was overall survival (OS); secondary endpoints included relapse-free survival (RFS), GVHD/relapse-free survival (GRFS), cumulative incidence of relapse (CIR), and transplant-related mortality (TRM). Relapse and TRM were analyzed using competing risk methodology. CRS occurred in 51% of patients. In the overall cohort, OS was numerically higher in patients with CRS but did not reach statistical significance. In contrast, among patients transplanted beyond first complete remission (CR1), CRS was significantly associated with improved OS (median not reached vs 7.6 months; p = 0.02). In this subgroup, RFS and GRFS also showed consistent trends in favor of CRS, although not statistically significant. The cumulative incidence of relapse was numerically lower in patients with CRS, without reaching statistical significance. TRM was comparable between groups, with no increase in early mortality. No differences were observed in acute or chronic GVHD. Notably, no patients received specific treatment for CRS, and clinical manifestations resolved following post-transplant cyclophosphamide, supporting an alloimmune origin of the syndrome. In conclusion, CRS after haplo-HSCT is associated with improved survival in patients with advanced disease, without increased TRM, and may represent a marker of early immune activation and graft-versus-leukemia effect.
Background:This study explores the impact of different immunoparesis states on early infection risk within 6 months of diagnosis in patients with newly diagnosed multiple myeloma (NDMM), aiming to inform clinical infection prevention strategies. Methods:A retrospective analysis was conducted on 213 NDMM patients (2016-2024). Immunoparesis was classified qualitatively (no, partial, and full immunoparesis) and quantitatively (with immunoglobulin reduction < 50% and ≥ 50%). Early infection rates and immunoparesis status were assessed using Kaplan-Meier survival curves. Cox regression models were applied to evaluate the independent prognostic effect of immunoparesis on infection risk. Results:Immunoparesis significantly increased the risk of early infections. In the qualitative analysis, infection rates were 15.8% for no immunoparesis, 53.1% for partial, and 53.8% for full immunoparesis (Log-rank P = 0.017). In the quantitative analysis, infection rates were 51.9% for < 50% immunosuppression and 54.2% for ≥ 50% immunosuppression, compared to 15.8% for no immunoparesis (Log-rank P = 0.017). Cox regression analysis showed that partial and full immunoparesis increased the risk of infection by 8.9-fold (HR = 8.9, P = 0.004) and 7.8-fold (HR = 7.8, P = 0.006), respectively. Similarly, < 50% and ≥ 50% immunosuppression increased infection risk by 8.67-fold (HR = 8.67, P = 0.005) and 7.95-fold (HR = 7.95, P = 0.005), respectively. Conclusion:Immunoparesis significantly increases early infection risk in NDMM patients. However, no significant risk gradient was observed relative to the breadth or depth of immunoparesis within this cohort. Monitoring and timely intervention for immunoparesis are essential for infection prevention.
A 54-year-old man of Albanian ethnicity presented with widespread osteolytic disease and a biclonal pattern on serum protein electrophoresis (SPEP), with markedly elevated IgG (3251 mg/dL), severe immunoparesis, and a markedly abnormal kappa/lambda free light chain ratio.
Immune checkpoint inhibitors have significantly improved outcomes in relapsed or refractory Hodgkin lymphoma (rrHL). Pembrolizumab, a programmed death-1 inhibitor, is generally well tolerated but may induce immune-related adverse events (irAE), including rare sarcoid-like reactions that can mimic disease progression. We report the case of a 30-year-old woman with refractory classical Hodgkin lymphoma (cHL) who developed pulmonary sarcoid-like granulomatous inflammation during pembrolizumab therapy.
Classical Hodgkin Lymphoma is one of the most curable neoplasms worldwide, particularly among young adults. Significant advances have been made to maximize treatment efficacy and minimize acute and long-term toxicities, including infertility, cardiovascular complications and secondary primary malignancies. Pretreatment prognostic stratification and interim PET response are the cornerstones of personalized treatment strategies. Circulating tumor cell-free DNA represents an investigational tool for genotyping Hodgkin Lymphoma at diagnosis and monitoring treatment response. An abbreviated course of polychemotherapy followed by involved-site/involved nodal radiotherapy continues to be the gold standard in early-stage diseases, while polychemotherapy remains the mainstay for the treatment of advanced-stage disease with or without the incorporation of novel agents, such as the anti-CD30 antibody-drug conjugate brentuximab-vedotin (BV) or the anti-PD1 checkpoint inhibitors (CPI) nivolumab and pembrolizumab. In elderly patients, treatment requires careful adaptation to minimize acute toxicities, often reducing the chemotherapy load or incorporating new targeted therapies. Although consolidation with autologous stem cell transplantation (ASCT) after salvage chemotherapy remains the standard approach in patients with chemosensitive relapsed/refractory cHL, significant improvements in response rate and duration have been achieved when BV and CPI are integrated into salvage regimens prior to ASCT or as post-transplant maintenance. Both classes of drugs are also approved as monotherapy in patients who are transplant-ineligible or have refractory/relapsed disease. Novel therapeutic approaches, including anti-CD30 CAR-T cells and the combination of the anti-CD30/CD16A bispecific antibody AFM13 with preactivated allogeneic cord blood-derived NK cells, are under investigation for patients who have failed the currently approved treatment options.
Background:An increased serum ferritin is a frequent finding in adults with β-thalassemia trait (BTT). However, whether such an increase is associated with a proportional increase in iron stores is unclear. Objectives:We aimed to evaluate liver iron stores in a consecutive cohort of BTT with hyperferritinemia who underwent magnetic resonance imaging (LICMRI) for clinical purposes. Methods:Sixty-six BTT subjects with hyperferritinemia were studied. Clinical, biochemical, and genetic evaluations were done to assess the cause of hyperferritinemia. LICMRI was classified as: grade-1= ≤3 mg/g (normal/mild); grade-2= >3≤7 mg/g (moderate); grade-3= >7 (severe). Results:80.3% showed normal/mild (n=29, 43.9%) or moderate LICMRI (n=24, 36.4%), while 19.7% (n=13) showed values >7 mg/g. The latter had lower haemoglobin concentration (p=0.004) and higher transferrin saturation and ferritin compared to subjects with lower LICMRI (p<0.001), while steatotic liver disease was more frequent in subjects with lower LICMRI grades (p=0.012). Liver cirrhosis was significantly more frequent in subjects with moderate/severe than in those with lower LICMRI grades (p=0.001 and p=0.025, respectively). We found a higher frequency of HFE and non-HFE iron-related genotypes (risk genotypes) in LICMRI grades 2-3 compared to none in LICMRI grade 1 (p=0.003 and p<0.0001, respectively). A regression analysis identified risk genotypes, liver cirrhosis, and BMI as significantly associated with LICMRI. Conclusions:Hyperferritinemia is common in BTT subjects, but major iron overload is limited to a minority of cases. They present associated genetic and acquired causes of iron accumulation and increased risk of liver damage.
Background:Screening for dysglycemia with an annual oral glucose tolerance test (OGTT) is recommended in transfusion-dependent β-thalassemia (β-TDT), but adherence in routine practice is low. Fasting surrogate indices of β-cell function and insulin sensitivity could offer a less burdensome alternative. Aims:To evaluate in adult β-TDT patients with normal fasting plasma glucose (FPG < 100 mg/dL): (i) the performance of fasting HOMA-2 indices (HOMA2-IR, HOMA2-%β, HOMA2-%S) and their disposition index as predictors of dysglycemia, and (ii) the comparative value of basal versus dynamic OGTT-derived markers (30-min and 1-h plasma glucose, insulinogenic index [IGI], IGI × ISI Matsuda index and IGI/HOMA2-IR), as predictors of hyperglycemia. Methods:A single-centre retrospective analysis of 42 β-TDT patients (19 males/23 females; mean age 29.2 ± 5.9 yr) with FPG < 100 mg/dL who underwent a standard 75-g 2-h OGTT between January 2011 and September 2025. Patients were classified as those with normal glucose tolerance (NGT; n = 19) or those with impaired glucose tolerance (IGT: n= 20) or thalassemia-related diabetes mellitus (Th-RDM: n = 3). Fasting and dynamic indices were compared by ANOVA and Mann-Whitney U test; associations were tested by Pearson/Spearman correlation and by three sequential exploratory multivariable linear regression models with 2-h plasma glucose as the dependent variable. ROC analysis with Youden's index identified optimal hypothesis-generating cut-offs. Results:Fasting HOMA2-IR, HOMA2-%β and HOMA2-%S did not differ significantly between NGT and hyperglycemic patients and were not independent predictors of 2-h plasma glucose. In contrast, in the total group, 30-min PG, 1-h PG, IGI, IGI × ISI Matsuda index and IGI/HOMA2-IR all differed significantly between groups (p: ≤ 0.0082) and were inversely correlated with 2-h PG. Receiver operating characteristic (ROC) analysis and area under the curve (AUC-ROC) were used to assess diagnostic performance of the most significant variables. The ROC-AUC cut-offs for predicting dysglycemia were 122.5 mg/dL for 30-min PG (sensitivity 0.91, specificity 0.52), 134 mg/dL for 1-h PG (0.95, 0.10), 5.7 for IGI × ISI Matsuda index (0.87, 0.47) and 1.33 for IGI/HOMA2-IR (0.87, 0.57). Conclusions:Fasting HOMA-2 indices alone are not reliable predictors of dysglycemia in β-TDT patients with PG < 100 mg/dL. The dynamic IGI/HOMA2-IR ratio and the 30-min/1-h post-load plasma glucose may help risk-stratify patients with β-TDT and normal fasting glucose; however, the proposed cut-offs should be regarded as hypothesis-generating, and prospective multicenter validation is required before these indices can be used to modify current OGTT screening recommendations.
