Yahya Büyükaşık

Objective: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for hematological malignancies; however, graft-versus-host disease (GVHD) remains a major complication. While donor T cells are central to GVHD pathogenesis, natural killer (NK) cells, via activating and inhibitory receptors, may also influence disease course. This study evaluated post-transplant changes in non-KIR receptor expression on NK cells and their association with GVHD. Materials and Methods: Twenty patients (M:3, F:13) who underwent allogeneic HSCT at Hacettepe University (2021–2024) were included. The mean age was 50, with a median follow-up of 26.1 months. Eleven patients received fully matched and nine haploidentical transplants; GVHD developed in 10 patients. Peripheral blood samples were collected at day 0 and on days 30, 100, and 180. Patients were followed for at least 6 months. Mononuclear cells were isolated, and non-KIR receptor expression in NK subsets was analyzed by flow cytometry. NK cells from days 0 and 30 were co-cultured with the K562 cell line to assess CD107a, perforin, and granzyme expression. Results: Eight AML, six ALL, four MDS, and two lymphoma patients were included. NKG2A and NKG2D decreased significantly (p=0.0001; p=0.0049). NKG2C declined until day 30, then increased. NKp30, NKp44, and NKp46 decreased. ILT-2 and ILT-4 also showed significant reductions (p=0.004; p=0.0001). Cytotoxicity analysis showed increased granzyme and decreased perforin and CD107a, with only perforin reduction significant (p=0.025). Increased NKp46 and NKp30 expression was associated with reduced GVHD risk (AUC: 0.819; 95% CI: 0.576–1.000). Conclusion: Allogeneic HSCT is associated with reduced NK cell non-KIR receptor and perforin expression. Although no significant relationship was found between GVHD development and receptor profile, changes in expression levels suggest that NK cells are affected by chronic inflammation. Higher NKp46 and NKp30 expression may indicate reduced GVHD risk, supporting their potential as biomarkers and the need for larger studies. Keywords: Graft-versus-host disease (GVHD), Hematopoietic Stem Cell Transplantation (HSCT), non-KIR receptor, NK cell

Aims: Pegylated interferon-α (PEG-IFN-α) offers improved pharmacokinetics compared with conventional interferon-α (IFN-α), yet real-world data on its clinical activity and safety across heterogeneous hematologic neoplasms are limited. This study aimed to evaluate the real-world efficacy, durability of response, and toxicity of PEG-IFN-α in patients with diverse hematologic neoplasms. Methods: This retrospective study evaluated the efficacy, duration of response, and toxicity of PEG-IFN-α using patient medical records and hospital electronic registries. Thirty patients were included: polycythemia vera (PV, n=12), essential thrombocytosis (ET, n=6), chronic myeloid leukemia (n=2), primary myelofibrosis (n=1), systemic mastocytosis (SM,n=3), hypereosinophilic syndrome (HES, n=1), Erdheim–Chester disease (ECD, n=4), and lymphomatoid granulomatosis (LYG, n=1). Results: PEG-IFN-α was initiated due to resistance to prior therapies in 12 patients (40%), intolerance or toxicity in 10 patients (33.3%), and as first-line treatment in 8 patients (26.7%). Among PV patients, a complete response was achieved in 41.6% and a partial response in 50%. In ET patients, 83.3% achieved a complete response, while 16.7% showed no response. All patients with SM demonstrated clinical improvement when PEG-IFN-α was used as first-line therapy. In ECD patients, follow-up PET imaging showed stable disease in two patients, partial response in one, and no response in one. Partial responses were also observed in patients with HES and LYG. Treatment-related toxicity occurred in 8 patients (26.6%) and led to treatment discontinuation in 6 patients (20%) (including cytopenias, influenza-like symptoms, and elevated liver enzymes). Conclusion: In this real-world cohort, PEG-IFN-α showed encouraging activity across several hematologic neoplasms, with toxicity and discontinuation rates in line with previously published series of conventional interferon-α; however, its clinical use remains limited by regulatory and access constraints.

This study challenges the static and linear assumptions of traditional prognostic models for diffuse large B-cell lymphoma (DLBCL), such as the International Prognostic Index (IPI). Analyzing 664 DLBCL patients treated with R-CHOP, the research explored the time-dependent and nonlinear effects of established risk factors. While the IPI maintained strong overall prognostic stability, its individual components exhibited dynamic behavior. ECOG performance score, beta-2 microglobulin (β2 M), and lactate dehydrogenase (LDH) were key predictors of early mortality, with their influence diminishing over time. Conversely, the importance of Ann Arbor stage and extranodal involvement grew, identifying them as markers of later risk. Notably, the study found a resurgence in the predictive power of β2 M after two years. Furthermore, restricted cubic spline modeling revealed significant nonlinear relationships between overall survival and age, LDH, and β2 M (all p < 0.001 for nonlinearity). The prognostic impact of baseline factors in DLBCL follows dynamic and nonlinear trajectories, challenging the one-size-fits-all approach of current risk scores. Future models should incorporate these temporal dynamics to provide a more accurate, personalized risk assessment.

Immunocompromised (IC) patients are at increased risk of herpes zoster (HZ; i.e. shingles) and subsequent complications which can significantly impact quality of life. While current evidence indicates a strong disease presence of HZ in Türkiye, literature on the management of HZ in this population is lacking. We conducted a survey with 6 disease experts from various medical specialties in Türkiye to understand their opinions on the burden of HZ and the challenges faced by IC patients, in order to establish a comprehensive and evidence-based expert consensus. Experts agreed that the burden of HZ is significant among IC patients in Türkiye. However, they identified a need for increased local epidemiological data to better understand the health impact of HZ in Türkiye. Improved dissemination of information regarding HZ to physicians was also highlighted to increase awareness of HZ. Strategies to enhance current practices and increase vaccine coverage should include incorporation of HZ vaccination into official guidelines and recommendations, with full or partial reimbursement for HZ vaccination in IC patients. Setting up official or society-initiated online platforms could also support ongoing collaboration and provide continuously updated guidelines reflecting the latest advances in HZ vaccination and disease management.

Accurate prediction of CNS relapse in DLBCL remains challenging despite existing models like IPI and CNS-IPI. This study aimed to develop a machine learning (ML)-based prognostic model. A retrospective cohort of 664 R-CHOP-treated DLBCL patients was analyzed; 44 (6.6%) experienced CNS relapse at a median of 9.3 months. ML models, including Random Survival Forests (RSF) and Gradient Boosting Machines (GBM), were developed and validated using the entire cohort (n = 664), irrespective of CNS relapse. RSF demonstrated high discriminative ability (C-index: 0.91) and low prediction error (Integrated Brier Score [IBS]: 0.057), while GBM yielded comparable performance (C-index: 0.88, IBS: 0.042), both outperforming traditional scores such as IPI and CNS-IPI. Key predictors included extranodal site number, high-risk organ involvement, and ECOG performance status, although ECOG lost significance in Fine and Gray competing risks analysis, likely due to early mortality. ML-based models offer enhanced predictive accuracy and support personalized CNS risk assessment in DLBCL.

Objective: To determine the independent prognostic influence of pre-treatment anemia severity in patients with acute myeloid leukemia. Patients and Methods: This was a retrospective evaluation of AML patients between January 2002 and May 2018 at a university hospital hematology clinic. The patients were divided into four groups: intensive treatment achieving complete remission (CR), intensive treatment without CR, non-intensive treatment, and supportive treatment. Baseline clinicodemographic features, laboratory data including serum hemoglobin levels, were collected. Baseline and post-treatment hemoglobin levels were compared according to treatment and across groups. A logistic regression analysis was also made to evaluate the influence of anemia on achieving a complete remission. Results: The mean hemoglobin level at the time of diagnosis was 8.5 g/dL (6.4 – 14.4). Although hemoglobin value was lower in the secondary AML subgroup, there was no significant difference between the groups at the time of diagnosis (p = 0.082). Hemoglobin values after induction chemotherapy were significantly different between treatment groups (p <0.001). When the variables predicting complete remission are examined by logistic regression, per 1 gr/dL increase in hemoglobin level at the time of diagnosis increased the probability of remission significantly (p = 0.047, OR = 1.13, 95% CI 1.07 - 1.24). Conclusion: A patient’s baseline pre-treatment serum hemoglobin level can predict the achievement of complete remission in AML patients. Anemia improves with induction chemotherapy, even without complete remission.

Invasive fungal infection (IFI) is an important cause of morbidity and mortality in acute leukemia patients. In the past few decades, the incidence of IFI has dramatically increased. Nevertheless, the management of IFI has become more complicated owing to changes in the epidemiology of fungal diseases and therapeutic regimens. Therefore, it is important to establish an appropriate strategy for centers that provide the diagnosis and treatment of acute leukemia patients based on scientific data and with available resources. In this study we investigated the incidence of IFI, pathogens, the use of diagnostic methods, and risk factors for IFI in acute leukemia patients over a 17-year period. A total of 502 acute leukemia patients (male/female: 57%/43%, mean age: 57.7 ± 15.5 years) hospitalized at adult and oncology hospitals between 2003 and 2020 were reviewed retrospectively. The incidence of proven and probable IFI was 13.2% (33.1%, when possible cases were included). The most common IFI was aspergillosis (49 patients, 9.7%), followed by candidemia, mucormycosis, and Pneumocystis jirovecii pneumonia. The galactomannan antigen test was positive in the serum of 39 (23.5%) patients and in bronchoalveolar lavage (BAL) fluid in 6 (3.6%) patients. Thirteen (7.8%) sputum cultures (11 Aspergillus spp. and 2 Candida spp.) and 4 (2.4%) BAL fluid (1 Aspergillus spp., 2 Candida spp., 1 P jirovecii) were positive for a fungal pathogen. Neutropenia, intensive care unit (ICU) follow-up and mechanical ventilation (MV) increased the risk of IFI by 3.5, 2.5, and 1.8 times, respectively. The median survival was 5 (range: 1.9–8) months. ICU follow-up shortened the survival by 12 months and increased the death risk by 2.49-fold. MV shortened survival by 57 months and increased the death risk by 3.82-fold. IFI remains a significant contributor to the morbidity and mortality in acute leukemia patients. Pulmonary involvement is the most common site. Neutropenia, ICU follow-up and MV are associated with an increased risk for IFI and mortality. We recommend in the IFI approach, to be aware of IFI in patients receiving intensive chemotherapy and/or recipients of hematopoietic stem cell transplantation, and to evaluate with microbiological, serological and radiological tests during the clinical follow-up.

We investigated the influence of a local guideline on the quality of febrile neutropenia (FN) management and the applicability of a computerized decision support system (CDSS) using real-life data. The study included 227 FN patients between April 2016 and January 2019. The primary outcome measure was the achievement of a 20% increase in the rate of appropriate empirical treatment of FN in bacteremic patients. The compatibility of the CDSS (the development of which was completed in November 2021) with local protocols was tested using standard patient scenarios and empirical antibiotic recommendations for bacteremic FN patients. In total, 91 patients were evaluated before (P1: between April 2016 and May 2017) and 136 after (P2: between May 2017 and January 2019) the guideline’s release (May 2017). The demographic characteristics were similar. Appropriate empirical antibacterial treatment was achieved in 58.3% of P1 and 88.1% of P2 patients (p = 0.006). The need for escalation of antibacterial treatment was significantly lower in P2 (49.5% vs. 35.3%; p = 0.03). In P2, the performance of the CDSS and consulting physicians was similar (CDSS 88.8% vs. physician 88.83%; p = 1) regarding appropriate empirical antibacterial treatment. The introduction of the local guideline improved the appropriateness of initial empirical treatment and reduced escalation rates in FN patients. The high rate of compliance of the CDSS with the local guideline-based decisions in P2 highlights the usefulness of the CDSS for these patients.

Introduction This study aimed to assess the incidence of hematologic malignancy (HM) among inflammatory arthritis (IA) patients receiving tumor necrosis factor inhibitors (TNFi) compared with the general Turkish population. Methods HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single-center biological disease-modifying anti-rheumatic drug (bDMARD) registry since 2005. Patients with IA, including rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis who had at least one visit after the TNFi were screened from 2005 to November 2021. Standardized incidence rates (SIR) were calculated after adjustment for age and gender and compared with the 2017 Turkish National Cancer Registry (TNCR). Results Of the 6139 patients registered in the HUR-BIO, 5355 used any TNFi at least once. The median follow-up duration was 2.6 years for patients receiving TNFi. Thirteen patients developed a HM on follow-up. In these patients, the median age at the IA onset was 38 (range, 26–67), and the median age at the HM diagnosis was 55.5 (range, 38–76). Patients using TNFi had an increased HM incidence (SIR 4.23, 95% confidence interval (CI) 2.35–7.05). Ten patients with HM were under 65 years of age. In this group, there was a higher incidence of HM in both men (SIR 5.15, 95% CI 1.88–11.43) and women (SIR 4.76, 95% CI 1.74–10.55). Conclusions The risk of HMs in inflammatory arthritis patients receiving TNFi was four times higher than in the general Turkish population.

Aim: To determine the unmet needs and challenges in management, diagnosis, treatment, follow-up and patient–physician communication in acute leukemia (AL). Materials & methods: The study was based ...