Advanced chronic kidney disease (CKD) is characterized by a complex hemostatic state in which thrombotic and bleeding risks coexist. As kidney function declines, balancing thrombotic protection against bleeding risk becomes increasingly challenging. Although atrial fibrillation is common and associated with a high stroke risk in advanced CKD, the net clinical benefit of anticoagulation remains uncertain because this population has been largely excluded from pivotal randomized trials. Existing risk scores incompletely capture CKD-specific and dynamic determinants of both thrombosis and bleeding. Observational data suggest potential advantages of apixaban over warfarin, whereas evidence for other agents remains limited. Recent randomized evidence has reinforced the difficulty of extrapolating antithrombotic strategies from the general cardiovascular population to advanced CKD. Future research should prioritize CKD-specific risk prediction, inclusion of advanced CKD populations in randomized trials, and safer anticoagulant strategies, including factor XI/XIa inhibitors.
Objective:This study aimed to compare differences in peripheral blood large granular lymphocytes (LGLs) between healthy donors and patients with large granular lymphocyte leukemia (LGLL), and explore methods to boost the sensitivity of peripheral blood smear examination for LGLL identification. Materials and Methods:We retrospectively analyzed 391 healthy donors and 53 LGLL patients from 2023 to 2024. Results:Results showed significant differences in LGL proportion, absolute count and its proportion in lymphocytes between the two groups (all P<0.001). There was no significant difference between smear and flow cytometric results. ROC curve analysis determined 24% LGL proportion as the cutoff value. Conclusion:Peripheral blood smear can be used for initial LGLL screening, and the thresholds of 0.5×10⁹/L LGL absolute count and 24% LGL proportion effectively screen LGLL patients.
Objective:Asparaginase is essential in acute lymphoblastic leukemia (ALL) therapy, but toxicity frequently necessitates formulation switching or discontinuation. This study evaluates real-world patterns of asparaginase use and the frequency and causes of formulation switching, and it assesses the impact of formulation switching and incomplete dosing on survival outcomes. Materials and Methods:We conducted a retrospective single-center study of 313 children with ALL treated according to Berlin-Frankfurt-Munster-based protocols between January 2009 and January 2024. Three asparaginase preparations were used: native Escherichia coli L-asparaginase, pegylated E. coli asparaginase, and Erwinia chrysanthemi asparaginase. We evaluated formulation changes or discontinuation, their causes, and their impact on event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR). To avoid reverse causation, patients unable to complete asparaginase because of an early event (induction death or refractory disease) were analyzed separately. The remaining patients were grouped as having received standard complete treatment, drug shortage or toxicityrelated formulation switch with preserved dose, or drug shortage or toxicity-related discontinuation with incomplete dose. Results:The median age of the patients was 6.9 years, 58.1% were male, and 86.6% had B-cell ALL while 13.4% had T-cell ALL. Asparaginase formulation change occurred for 78 patients (24.9%), increasing across risk groups (standard: 4.0%, intermediate: 15.4%, high: 42.9%), most often due to hypersensitivity (64 patients, 20.4%). After a median follow-up of 5.2 years, 5-year OS and EFS for the whole cohort were 87.4% and 81.6%, respectively. Among 302 evaluable patients, 5-year EFS was 83.1% in the standard complete treatment group, 93.8% in the formulation-switch group, and 69.1% in the incomplete treatment group (p=0.027 for three-group comparison); the corresponding 5-year CIR rates were 13.3%, 2.2%, and 15.9%. Formulation switch with preserved dose was not associated with inferior EFS (adjusted hazard ratio [HR]: 0.23, 95% confidence interval [CI]: 0.07-0.77), and discontinuation showed a numerically lower EFS that was not statistically significant (HR: 1.03, 95% CI: 0.36-2.91). Conclusion:Formulation switching with preserved total cumulative exposure did not compromise outcomes, supporting the safety of substituting alternative preparations to maintain asparaginase exposure. Incomplete treatment showed a nonsignificant trend toward inferior EFS that warrants confirmation in larger cohorts. Ensuring access to alternative asparaginase formulations is critical, particularly where drug supply is constrained.
Objective:We aimed to develop a survival prediction system integrating radiomics and clinical features for newly diagnosed multiple myeloma (MM) and to compare the performance of different feature sets and algorithms in the early prediction of progression-free survival (PFS). Materials and Methods:This study retrospectively included 300 MM patients between June 2022 and June 2024, with their baseline positron emission tomography, computed tomography, and magnetic resonance imaging radiomics features and clinical variables collected. Following construction of a radiomics-based risk score (Rad-score), seven machine learning-based survival models were established using the clinical feature set, the image feature set, and the integrated feature set. Results:The fusion feature set-based gradient boosting model (GBM) showed numerically favorable overall performance in predicting 12-month PFS, suggesting that the integration of radiomics and clinical variables may provide complementary predictive information for early risk stratification. The model effectively distinguished high-, intermediate-, and low-risk patients (log-rank p<0.001), and calibration curve analysis and decision curve analysis revealed favorable calibration and high clinical net benefits. Shapley additive explanations analysis showed that the Rad-score was one of the most important features in the model, indicating that radiomics information may contribute prognostic value within the integrated feature space. β2-microglobulin, age, lactate dehydrogenase, blood calcium, platelet count, and hemoglobin were also identified as key contributing features. Conclusion:The integration of radiomics and clinical variables may improve early PFS prediction in MM patients. The GBM using fused features showed relatively good discriminative ability, potential clinical applicability, and favorable interpretability.
Pruritus may be a debilitating symptom in cases of myeloproliferative neoplasm (MPN). Since mast cells (MCs) play a pivotal role, we hypothesized that bone marrow (BM) MCs contribute to the occurrence of pruritus. In this exploratory study, untreated MPN patients were included. BM aspirate/biopsy/blood samples and responses to the MPN-Symptom Assessment Form were obtained. Thirty-two patients were included (essential thrombocythemia, n=19; polycythemia vera, n=7; primary myelofibrosis, n=6). Eleven had clinically significant pruritus (35%). The absolute MC count and proportion per total nucleated BM cells were significantly higher in patients with pruritus compared to those without (mean of 25.5 vs. 58.1 MCs/mm2, p=0.032 and 0.59% vs. 1.66%, p=0.041, respectively). MC immunophenotypes and serum levels of tryptase, interleukin-6, tumor necrosis factor alpha, and soluble CD117 were not correlated. Thus, this study showed that absolute and relative MC numbers are increased in cases of MPN with pruritus. However, whether MCs play a pathophysiological role in causing pruritus or are bystanders remains to be determined.
This study evaluated the current status, clinical capacity, and key barriers related to chimeric antigen receptor T-cell (CAR-T) therapy in Türkiye with the aim of guiding national policy development. From June 2023 to March 2024, the Scientific Subcommittee on Cell and Gene Therapies of the Turkish Society of Hematology conducted two nationwide online surveys and held three multidisciplinary meetings with contributions from hematologists, basic scientists, and key stakeholders. Survey findings were integrated with the meeting outputs and recent regulatory developments. Surveys indicated a marked gap between the estimated annual need (about 507 patients) and actual access to CAR-T therapy. Between 2019 and March 2024, only 23 patients in Türkiye received CAR-T therapy. Major barriers included high treatment costs, insufficient infrastructure, and a limited number of trained personnel. Expert meetings further highlighted challenges with regulatory pathways, reimbursement, and the need for standardized production and clinical protocols. Despite these limitations, participants demonstrated strong clinical readiness and consensus on the need to improve access. The implementation of CAR-T therapy in Türkiye continues to be impeded by structural and economic limitations. It is imperative to develop a strategic national roadmap that encompasses: 1) the establishment of a national academic CAR-T network, 2) the securing of sustainable funding and legal frameworks, 3) the implementation of hospital-exemption pathways, 4) the development of a centralized registry, 5) the expansion of structured training programs, and 6) the enhancement of international collaborations. These measures are fundamental for the sustainable integration of this therapy into clinical practice.
Objective: Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for relapsed or refractory (R/R) Hodgkin lymphoma despite advances with novel therapeutic agents such as brentuximab vedotin (BV) and immune checkpoint inhibitors (CPIs). This study aimed to assess the benefit of prior exposure to novel therapeutic agents prior to allo-HCT in patients with R/R Hodgkin lymphoma. Materials and Methods: This study's retrospective multicentric analysis involved 70 patients with R/R classical Hodgkin lymphoma who underwent allo-HCT. Results: The analyzed patients were split into two main treatment cohorts: Era 1 (2004-2010) included 16 patients, while Era 2 (2011-2021) included 54 patients. Within the total patient cohort, 63 patients had previously received autologous stem cell transplantation. Forty patients were administered only BV (n=29) or BV preceding CPI (n=11) before allo-HCT. A median follow-up duration of 64 months (range: 40.7-87.3) revealed a 100-day non-relapse mortality (NRM) rate of 26%, with 3-year overall survival (OS) and progression-free survival (PFS) rates of 39% and 28%, respectively. Allo-HCT with haplotype-matched donors was linked to better OS and PFS. Post-transplant cyclophosphamide as a prophylactic approach for graft-versus-host disease significantly improved OS and PFS. A complete response during the post-transplant period significantly improved OS and PFS. Better OS, better PFS, and reduced NRM were observed both before and after allo-HCT in patients receiving BV and CPIs, although statistical significance was not reached. The OS and PFS curves and the NRM rates were similar between Era 1 and Era 2. Conclusion: Allo-HCT is a potentially practical therapeutic approach for the treatment of patients with R/R Hodgkin lymphoma.
Objective:This study aimed to investigate the relationship between the human leukocyte antigen (HLA) system and ABO blood groups in healthy donors. A comparative analysis of HLA immunogenetic architecture was performed between A Rh(+) and O Rh(+) individuals to examine potential population-level variations. Materials and Methods:This retrospective study included 346 unrelated healthy donors registered with the Eskişehir Osmangazi University Tissue Typing Laboratory between 2017 and 2025. Participants were 50.7% female and 49.3% male, with a mean age of 41.2±14.8 years. Detailed HLA immunogenetic analyses were performed for 249 donors, including 142 A Rh(+) and 107 O Rh(+) individuals. The HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci were genotyped using the DNA-based polymerase chain reaction sequence-specific oligonucleotide method. Allele frequencies, haplotype distributions, Hardy-Weinberg equilibrium (HWE), and linkage disequilibrium (LD) patterns were analyzed using PyPop software. Results:Allele distributions were broadly similar between groups. The HLA-DRB1*16 allele was enriched in A Rh(+) donors (8.8% vs. 4.2%, p=0.049), while HLA-B*49, HLA-DPB1*13, and HLA-DPB1*01 alleles were enriched in O Rh(+) donors (p=0.032, 0.022, and 0.015, respectively). LD patterns differed between the groups [A Rh(+): DQB1~DPB1, p=0.038; O Rh(+): HLA-A~DQB1, p=0.019], and all loci were in HWE (p>0.05). Conclusion:The analysis indicated that A Rh(+) and O Rh(+) donors share a largely similar HLA genetic background, with modest but detectable differences in selected class I and class II HLA alleles and LD patterns. These subtle variations likely reflect minor population heterogeneity rather than distinct ancestry and may aid in donor matching efforts and the interpretation of population-based immunogenetic association studies.
Objective:Febrile neutropenia (FN) in pediatric oncology is a clinically heterogeneous syndrome in which early antibiotic escalation decisions are frequently driven by non-specific severity cues. We aimed to identify baseline clinical phenotypes of pediatric FN, to describe early glycopeptide escalation patterns across these phenotypes, and to examine their associations with short-term outcomes and acute kidney injury (AKI). Materials and Methods:We conducted a retrospective cohort study including 106 FN episodes experienced by 82 pediatric oncology patients initially treated with piperacillin-tazobactam monotherapy. Baseline clinical and laboratory variables available within the first 6 hours of FN onset were used for unsupervised k-means clustering to derive latent clinical phenotypes. Early glycopeptide escalation was defined as the initiation of vancomycin or teicoplanin within 48 hours. Associations with clinical outcomes on day 7 and AKI were evaluated using multivariable cluster-robust regression and inverse probability of treatment weighting. Results:Three distinct FN phenotypes were identified: a high-inflammatory/mucositis-dominant phenotype (39.6%), a hemodynamically severe phenotype (22.6%), and a lower-severity phenotype (37.7%). Early glycopeptide escalation occurred in 26.4% of episodes and was disproportionately concentrated in the high-inflammatory and hemodynamically severe phenotypes. AKI developed in 10.4% of FN episodes and clustered predominantly within escalation-prone phenotypes. After adjustment, early escalation was not associated with improved day-7 clinical success but was associated with a higher observed risk of AKI. Conclusion:Pediatric FN comprises distinct clinical phenotypes that differentially drive antibiotic escalation behavior and renal injury risk. A phenotype-informed approach may help to optimize escalation decisions and potentially reduce preventable toxicity. However, given the observational design of this study, these associations should be interpreted with caution.
