Fatma Keklik Karadağ

Background: T-cell lymphomas (TCLs) constitute a heterogeneous group of mature T-cell neoplasms characterized by aggressive clinical behavior and poor outcomes, particularly in the relapsed/refractory (R/R) setting. Belinostat is a pan-HDAC inhibitor approved for R/R peripheral T-cell lymphomas. In this retrospective study, we analyze the real-world outcomes of single-agent belinostat in Turkish patients with R/R TCLs. Methods: Patients with R/R TCLs across Turkey who received at least one course of belinostat were included in the study. The primary end point was the overall response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS) and duration of response (DOR). Results: A total of 59 patients with R/R TCL were enrolled in the study, with a median age of 62 years. The median number of previous lines of therapy before belinostat was 2.5. The ORR for belinostat was 30.5% in the overall study cohort. Response assessment was available in 53 patients, among whom the ORR was 34% (18/53). The median PFS was 3 months. The median OS was 12 months, and the median DOR was not reached in responders. At least one adverse event occurred in 39.0% of patients. Conclusions: Belinostat produced objective responses in a subset of patients. These findings support belinostat as a potential individualized treatment option rather than a broadly effective standard for all patients with R/R TCLs. This multicenter real-world study demonstrates that the observed response rates closely mirror those reported in prospective clinical trials, confirming the reproducibility of belinostat efficacy in routine clinical practice.

Background: This study aimed to assess intergenerational differences in joint health and functional independence among adults with hemophilia and to examine the relationship between prophylaxis timing, dose intensity, and treatment adherence and long-term joint outcomes. Methods: A retrospective study was conducted including 91 adult patients with hemophilia A or B. Participants were classified into generational cohorts within different treatment eras. Joint health and functional status were assessed using the Hemophilia Joint Health Score (HJHS) and the Functional Independence Score in Hemophilia (FISH). Statistical analyses included correlation analyses, subgroup comparisons, and general linear models; subgroup analyses were considered exploratory. Results: The median age was 38 years, and prophylaxis was initiated at a median age of 27 years. Patients had a mean annual bleeding rate of 11.1, with a median of 2 joints affected per year, most commonly the ankles, knees, and elbows. The median prophylaxis dose was 20.8 IU/kg, and bleeding episodes significantly decreased in patients requiring dose escalation (P = .007). Higher joint scores were associated with poorer functional outcomes and a greater number of bleeding joints. Joint health and functional outcomes differed significantly across generations (P < .001), with worse outcomes in older cohorts. Follow-up showed no significant improvement over 1 year, although baseline and follow-up joint scores were strongly correlated (P < .001). Conclusion: In adults with hemophilia, delayed prophylaxis initiation was associated with poorer joint and functional outcomes. The observed intergenerational differences likely reflect historical variations in access to prophylaxis and treatment practices. Although individualized dose escalation improved bleeding control, established joint damage showed limited short-term reversibility. Cite this article as: Demirci Z, Soyer N, Keklik Karadağ F, Arslan A, Saydam G, Şahin F. Dose or timing? The role of prophylaxis in preventing joint bleeds in hemophilia: a cross-generational comparative analysis. Eurasian J Med. 2026, 58(4), 1208, doi: 10.5152/eurasianjmed.2026.251208.

Aims: Despite advances in hemophilia management, maintaining optimal treatment adherence remains a significant challenge, particularly when access to healthcare services is limited. To evaluate treatment adherence among adult patients with hemophilia during a period of restricted access to healthcare services, with particular emphasis on the roles of health literacy and communication with healthcare professionals. Methods: A total of 128 adult patients with moderate or severe hemophilia were enrolled in this cross-sectional study. Treatment adherence was assessed using the Validated Hemophilia Regimen Treatment Adherence Scale–Prophylaxis (VERITAS-Pro), which evaluates six domains: Time, Dose, Plan, Remember, Skip, and Communicate. Self-reported adherence, infusion practices, annual bleeding rate (ABR), age, and treatment-related variables were analyzed. Pearson correlation analysis and group comparisons were performed to examine associations between variables. Results: The median age of participants was 39 years (interquartile range [IQR]: 32–47). Most patients had hemophilia A (84.4%) and severe disease (77.3%), and 82.8% reported current target joints. The mean VERITAS-Pro total score was 47.8 ± 9.7, with 85.9% classified as adherent. High adherence was observed in timing (85.9%), planning (93.8%), remembering (93.0%), and skipping (85.9%), whereas communication represented the weakest adherence domain. Patients with higher ABR demonstrated significantly poorer communication scores (p = 0.007). Self-infusion was associated with significantly better adherence across multiple domains, including total score, timing, and planning (p < 0.05). Infusions administered at the beginning of the day were also associated with higher adherence. Age showed a weak, non-significant correlation with total adherence scores (r = 0.144, p = 0.104). Conclusion: Structured infusion routines and self-infusion practices appear to improve treatment adherence among adult patients with hemophilia. Communication with healthcare professionals remains a critical challenge, particularly among patients with higher bleeding frequency. Interventions targeting patient–provider communication may further enhance adherence outcomes

Background and Objectives: Peripheral cytopenia occurs in approximately 2% of the population; however, in up to 0.9%, no cause is identified by conventional tests. Next-Generation Sequencing (NGS) detects somatic variants consistent with clonal hematopoiesis (CH). We aimed to determine the prevalence of CH and pre-myelodysplastic syndrome (pre-MDS) using a 51-gene panel with histopathological assessment. Materials and Methods: Bone marrow samples from 96 consecutive patients evaluated for cytopenia were retrospectively analyzed for genetic alterations. Results: In the overall cohort (n = 96), the median follow-up was 8.1 months (range, 1–20). A total of 37 (39%) out of 96 patients were diagnosed with idiopathic cytopenia of undetermined significance (ICUS), 9 (9%) with clonal cytopenia of undetermined significance (CCUS), 9 (9%) with clonal cytopenia and monocytosis of undetermined significance (CCMUS), 34 (36%) with myelodysplastic syndrome (MDS), and 7 (7%) with myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Among 41 patients in whom no cytogenetic abnormalities were detected by fluorescence in situ hybridization (FISH), somatic variants were identified by NGS. In CCUS, 88% of patients had a single variant, most commonly ASXL1 (44%), followed by TET2 (22%). In CCMUS, ASXL1 and DNMT3A (each 25%) were the most frequent variants. The mean variant allele frequency (VAF) was higher in MDS (33.4%) than in CCUS/CCMUS (13.6%). In MDS patients aged 60 years and older, a higher number of variants were found compared to patients aged less than 60 years (p = 0.028). RUNX1 variants (n = 8) were associated with leukopenia (p = 0.012). Patients with SRSF2 variants (n = 4) had significantly poorer progression-free survival (p = 0.001). EZH2 and SETBP1 variants were associated with inferior overall survival (p = 0.04 and p = 0.019, respectively). In MDS patients (n = 34), thrombocytopenia (plt < 100.000) was associated with shorter PFS (p = 0.005). Conclusions: Given that pre-MDS conditions are considered predictors of hematologic malignancies, conventional diagnostic workup may be insufficient to accurately identify these entities, whereas NGS provides significant additional diagnostic value.

Background and Objectives: Systemic mastocytosis (SM) is a clonal mast cell disorder characterized by abnormal mast cell accumulation and activation in multiple organs, leading to mediator-related symptoms, including anaphylaxis. Drug hypersensitivity reactions (DHRs) are a major clinical challenge in SM, but their frequency and characteristics remain undefined. This study aimed to evaluate the frequency of drug allergy, identify high-risk drug groups, investigate reaction characteristics, and examine the relationship between drug reactions, baseline serum tryptase levels, and SM subtypes in patients with SM. Materials and Methods: We retrospectively analyzed 34 patients diagnosed with SM between 2009 and 2024 at Ege University Faculty of Medicine. Clinical features, SM subtypes, baseline serum tryptase levels, and DHR characteristics were recorded. Reactions to antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, anesthetics, radiocontrast media (RCM), and COVID-19 vaccines were graded using the Ring and Messmer anaphylaxis classification. Results: Among 34 patients, the mean age was 48.6 ± 13.3 years, 53% were male, and 10 (29.4%) had DHRs. The most common culprit drugs were NSAIDs (17.6%) and β-lactam antibiotics (14.7%). Anaphylaxis was the predominant reaction, frequently associated with hypotension. In 5 patients (14.7%), drug-induced anaphylaxis was the initial and only manifestation of SM. No hypersensitivity reactions occurred to quinolones, general anesthetics, or COVID-19 vaccines. Median baseline tryptase was 50.25 µg/L (min–max: 8.59–200.00) overall, and 41.85 µg/L (min–max: 19.00–200.00) among those with DHRs. Conclusions: Patients with SM are at increased risk of severe DHRs, particularly to NSAIDs and beta-lactam antibiotics. In some patients, drug allergy may be the first and only manifestation of SM. Measurement of baseline serum tryptase is essential in patients with drug-induced anaphylaxis. A comprehensive allergy assessment, including tolerance testing and individualized counseling, is crucial to ensure safe pharmacological management.

Large B-cell lymphoma (LBCL) patients who fail frontline therapy (R/R-LBCL) experience highly unfavorable outcomes. The development of T-cell redirecting therapies is rapidly evolving this outlook. However, costs and infrastructural challenges limit access to such innovative therapies. This study was conducted to document the shortcomings of management in the absence of regular access to T-cell redirecting therapies in a contemporary patient population and define subgroups with the most urgent need for accessing innovative treatments. The second-line management and outcomes of a large real-world LBCL cohort from Türkiye were retrospectively analyzed with the participation of nine centers from four different geographical regions. Despite the contemporary period (2012-24), there was no regular access to novel agents. The median PFS-2 was 6.9 months. Less than a quarter of patients (24.3%) received transplantation following a response to second-line therapy, the only subgroup who benefited from the standard care (2-year PFS-2: 67.8%). The remaining 295 patients (75.7% of the cohort) had a median survival of 6.1 months and a 2-year PFS-2 of 10.3%. Progression within a year from diagnosis, non-curative intent at second line, and failure of curative second-line therapy were key adverse features for a dismal prognosis, with median survival durations of 8.8, 2, and 7.4 months, respectively. The current therapeutic strategy of intensive chemoimmunotherapy followed by autologous transplantation yields a reasonable chance of survival for only a fifth of patients. The findings emphasize the urgent need for expanding access to T-cell redirecting approaches in R/R LBCL for early progressors, transplant-ineligible cases, those who fail intensive second-line regimens.

Background: Classical Hodgkin lymphoma (cHL) demonstrates high survival rates with the ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine); however, the use of bleomycin is associated with a significant risk of pulmonary toxicity. The Risk-Adapted Treatment of HL (RATHL) trial demonstrated that omitting bleomycin in patients with favorable interim Positron Emission Tomography (PET-CT) results did not adversely affect survival outcomes. In this study, we present real-world data from advanced-stage HL patients treated according to the RATHL protocol. Methods: This multicenter, retrospective study included newly diagnosed cHL patients with Ann Arbor stage IIB–IV disease or stage IIA disease with bulky disease or with involvement of three or more sites, enrolled from 29 centers across Türkiye. The analysis focused on patients whose initial treatment was de-escalated from ABVD to AVD (bleomycin was omitted). Data were collected on demographic and clinical prognostic characteristics, interim PET-CT findings (evaluated using the Deauville score), progression-free survival (PFS) and overall survival (OS). Survival outcomes were assessed using Kaplan–Meier analysis. Results: A total of 379 patients were included, with a median age of 34 years (range: 18–78). Following interim PET-CT assessments (After 2 cycles of ABVD), Deauville scores were 1 in 39.8% of patients, 2 in 39.1%, and 3 in 21.1%. Based on these results, bleomycin was omitted immediately after interim PET-CT in 73.9% of patients, after one additional ABVD cycle in 12.1%, and after two additional cycles in 14%. The median follow-up duration was 28 months (range: 6–96). The 3-year PFS and OS rates were 86.0% and 96.1%, respectively. Patients with Deauville scores of 1–2 had a 3-year PFS rate of 87.6%, compared to 79.8% in those with a score of 3 (p = 0.087). Increased age, poor Eastern Cooperative Oncology Group Scale (ECOG) performance status, bulky disease, and higher International Prognostic Scores (IPS) were significantly associated with inferior OS (p < 0.05). There were no significant differences in OS among patients who received 2, 3, or 4 cycles of ABVD. However, among patients treated with 2 cycles of ABVD, both extranodal involvement (p = 0.039) and higher IPS (p = 0.002) were significantly associated with decreased PFS. Conclusions: Our findings demonstrate that PET-guided de-escalation of bleomycin after two cycles of ABVD is feasible, effective, and safe in real-world multicenter practice in Türkiye. The survival outcomes are comparable to those reported in the RATHL study, reinforcing the role of interim PET-CT in guiding individualized therapy. However, patients with high IPS or extranodal involvement may require more tailored management strategies.

Aim: The study aimed to evaluate the clinical outcomes of chronic myeloid leukemia (CML) patients treated with imatinib at Ege University Department of Hematology over an eight-year period. Material and Methods: This observational retrospective study included 72 chronic phase CML patients aged over 18 years, treated with imatinib. Patients in the blastic or accelerated phases were excluded. Clinical, socio-demographic, and laboratory data were collected from the patient files. Patients were divided as early chronic phase (treated with imatinib within 6 months of diagnosis) and late chronic phase (started imatinib therapy at least 6 months after diagnosis). Hematologic, molecular, and cytogenetic responses at 3, 6, 12, and 18 months of imatinib therapy were recorded. Data analysis was performed using SPSS version 16.0. Results: Hematologic response at 3 months with imatinib was 80.5%, increasing to 94.7% at following months. Complete cytogenetic remission (CCyR) was achieved in 80% of patients within the 12 months. Overall response rate was 83.3% with a median follow-up of 10 years. The incidence of adverse events was 30.5%, compromising mostly non-hematologic toxicities such as edema and skin changes. Despite the adverse events, imatinib demonstrated significant clinical benefits comparable to second-generation tyrosine kinase inhibitors (TKIs). Conclusion: Over a decade has passed since our study was designed, yet imatinib continues to be a cornerstone in the treatment of chronic myeloid leukemia (CML). Imatinib is still an effective frontline therapy for CML, with high response rates, cost-effectivity and manageable toxicities.

Introduction: Transfusion‐dependent thalassemia (TDT) is most commonly caused by defects in beta globin chain production. Iron overload, hypogonadism, vitamin D deficiency, adverse effects of desferrioxamine treatment, and delayed puberty due to loss of bone mass are the main complications of TDT. In the present study, we aimed to investigate bone complications and precursor markers in TDT patients. Materials and Methods: Our retrospective study included 93 patients, aged between 18 and 45, who were followed up in a tertiary care institution and did not have any disease other than TDT. The patients’ BMD values and biochemical parameters were compared. Results: Osteoporosis was observed in 33 of 93 patients, and the mean transferrin saturation of patients with osteoporosis was 60%, and the mean transferrin saturation of patients without osteoporosis was 42%. Patients with osteoporosis had transferrin saturation that was observed to be considerably higher than that of the group without osteoporosis ( p = 0.006), with an average of 60%. Conclusion: Our investigation has demonstrated that in patients with TDT, elevated transferrin saturation may be a sign of osteoporosis.