| REVIEW | |
| 1. | A Narrative Review on the Approach to Hospital-Acquired Venous Thromboembolism in Pediatric Trauma and Critically Ill Children Robert Marcel T. Huibonhoa, E. Vincent S. Faustino doi: 10.4274/tjh.galenos.2025.2025.0365 Pages 256 - 264 Pediatric traumas and critical illnesses are known to confer increased risk for hospital-acquired venous thromboembolism (HA-VTE) in children. The development of HA-VTE in children is associated with increased mortality and disabling co-morbidities. In this narrative review, we discuss the current literature on HA-VTE in children with severe trauma and those who are critically ill. The pediatric literature in this field continues to grow with randomized trials and guidelines actively being developed. We describe the available data related to the frequency of HA-VTE specific to these populations, as well as the pathophysiological concepts and considerations for its development and management. We outline an approach to HA-VTE in these two groups by delving into risk assessment and the identification of risk factors that accrue in these children, the need to assess for thromboprophylaxis and balance its risks and benefits, the clinical presentation and imaging modalities to confirm the diagnosis of HAVTE, and management principles for developed HA-VTE. We use some of the currently available guidelines, including those of the Eastern Association for the Surgery of Trauma and Pediatric Trauma Society and the recently updated 2024 American Society of Hematology/ International Society on Thrombosis and Haemostasis guidelines on the management of VTE in children, to aid in our discussion. |
| ORIGINAL ARTICLE | |
| 2. | A Large Room for Improvement in the Management of Relapsed/ Refractory Large B-Cell Lymphoma in Türkiye: Real-World Outcomes in a Setting Without Access to T-Cell Redirecting Therapies Umut Yılmaz, Mehmet Sinan Dal, Turgay Ulaş, Elif Birtaş Ateşoğlu, Fatma Keklik Karadağ, Meral Uluköylü Mengüç, Esra Terzi Demirsoy, Simge Erdem, Ebru Pekgüç, Taner Tan, Uğur Hatipoğlu, Eda Nuhoğlu Kantarcı, Merve Apaydın Kayer, Ahmet Bahadır Ak, Serdar Örnek, Ali Durdu, Abdulkadir Şahin, Emre Osmanbaşoğlu, Nazik Okumuş, Tuğba Zorlu, Mert Seyhan, Mustafa Murat Özbalak, Tuğrul Elverdi, Asu Fergün Yılmaz, Derya Demir, Deniz Gören, Sinem Civriz Bozdağ, Tayfur Toptaş, Işık Atagündüz, Mustafa Nuri Yenerel doi: 10.4274/tjh.galenos.2025.2025.0352 Pages 265 - 280 Objective: Patients with large B-cell lymphoma (LBCL) who are relapsed/refractory (R/R) after frontline therapy have traditionally experienced highly unfavorable outcomes. The development of T-cell redirecting therapies is rapidly changing that outlook, but costs and infrastructural challenges limit access to these 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 the subgroups with the most urgent need for accessing innovative treatments. Materials and Methods: The second-line management strategies and outcomes of a large real-world LBCL cohort from Türkiye were retrospectively analyzed with the participation of 9 centers from 4 different geographical regions. Results: Despite the contemporary nature of the treatment strategies (2012-2024), there was no regular access to novel agents. The median progression-free survival after the first progression (PFS- 2) was 6.9 months. Fewer than one-fourth of all patients (24.3%) received transplantation following a response to second-line therapy, constituting the only subgroup to benefit from standard care (2-year PFS-2: 67.8%). The remaining 295 patients (75.7% of the cohort) had median survival of 6.1 months and 2-year PFS-2 of 10.3%. Progression within a year from diagnosis, non-curative intent at the second line of therapy, 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. Conclusion: The current therapeutic strategy of intensive chemoimmunotherapy followed by autologous transplantation yields a reasonable chance of survival for only one-fifth of patients. The findings of this study emphasize the urgent need for expanding access to T-cell redirecting approaches in R/R LBCL for early progressors, transplant-ineligible cases, and patients who fail intensive secondline regimens. |
| 3. | All-Cause and Exacerbation-Related Readmissions in Thrombotic Microangiopathy Requiring Plasmapheresis: A Population-Based Cohort Study Alexander R. Thebert, Toru Yoshino, Sae X. Morita, Misa Ito, Ayman Qasrawi, Hirotaka Kato doi: 10.4274/tjh.galenos.2025.2025.0317 Pages 281 - 289 Objective: Thrombotic microangiopathy (TMA) is a serious condition characterized by microangiopathic hemolytic anemia and thrombocytopenia, with high exacerbation rates. This study examined all-cause and exacerbation-related readmission risks among patients hospitalized with TMA requiring plasmapheresis. Materials and Methods: Secondary analysis of the 2020 Nationwide Readmission Database was conducted, including discharge data from non-federal hospitals in 31 U.S. states. Patients aged 18 years or older admitted non-electively with a primary or secondary diagnosis of TMA requiring plasmapheresis were included. Exacerbationrelated readmission was defined as subsequent admission requiring plasmapheresis within 7 or 30 days after the original discharge. Multivariable logistic regression and Cox proportional hazards models were used to assess readmission risks, adjusting for demographics, comorbidities, and predisposing factors. Results: Among an estimated 1393 patients, 791 (56.8%) had predisposing conditions. All-cause readmissions were more frequent in patients with predisposing conditions (26.2% vs. 21.9%), while exacerbation-related readmissions were more common in TMA-only patients (9.0% vs. 3.4% at 7 days; 13.7% vs. 6.4% at 30 days). Most exacerbations occurred within 14 days after discharge. No patients treated with caplacizumab experienced exacerbation. TMA-only patients had a 2.1-times higher risk of 30-day exacerbation-related readmissions (adjusted hazard ratio: 2.10, p=0.04). Rural residence and patient-directed discharge were potential risk factors for exacerbation-related readmissions. Conclusions: These findings highlight the need for improved postdischarge care and treatment strategies to prevent readmissions. Further studies should explore interventions to reduce exacerbationrelated readmissions, particularly in high-risk populations. |
| 4. | Arterial Thrombosis in Patients with Primary Immune Thrombocytopenia: A Nationwide Study Ufuk Demirci, Elif Gülsüm Ümit, Burak Dumludağ, Melda Cömert, Rafiye Çiftçiler, Deniz Ozmen, Muhlis Cem Ar, Serkan Güven, Özge Soyer, Tekin Güney, Zeynep Tuğba Karabulut, Abdulkerim Yıldız, Samet Yaman, Fatma Aykaş, Volkan Karakuş, Yıldız İpek, Güven Yilmaz, Sevil Sadri, Mehmet Baysal, Mehmet Can Uğur, İbrahim Ethem Pınar, Ahmet Muzaffer Demir doi: 10.4274/tjh.galenos.2025.2025.0268 Pages 290 - 298 Objective: Primary immune thrombocytopenia (pITP) is an acquired bleeding disorder involving decreased numbers of platelets due to platelet destruction or impaired production. The clinical presentation of pITP can be multifaceted and thrombotic events may rarely manifest. Thrombosis can develop with treatment or during the untreated period. The primary objective of this study was to examine the frequency of arterial thromboembolic events (ATEs) in patients with pITP. We also aimed to evaluate the risk factors in these patients and the effect of ITP treatments on ATEs. Materials and Methods: The study was designed as a retrospective multicenter study conducted under the guidance of the Turkish Society of Hematology’s Scientific Subcommittee on Hemostasis- Thrombosis. Patients over the age of 18 with pITP who subsequently developed ATE while undergoing follow-up for pITP were evaluated. Results: A total of 2,178 patients with pITP were screened and 37 patients (1.7%) were observed to have developed ATE. The mean age was 62 years. Fifteen (40.5%) of the patients who developed ATEs were not receiving pITP treatment at the time of thromboembolism. Among the patients receiving pITP treatment at the time of the ATE, 9 (24.3%) were receiving eltrombopag and 10 (27%) were receiving corticosteroids. Compared to patients who did not develop ATEs, multivariate analysis revealed that the presence of hypertension, comorbidity, and history of venous thromboembolism statistically significantly increased the risk of developing ATEs (p=0.008, p=0.018, and p=0.038, respectively). Conclusion: The risk of ATEs may increase in pITP patients both during and without treatment. It is important to inquire thoroughly about the presence of comorbidities, atherosclerotic risk factors, hypertension, and history of thrombosis in these patients at the initiation of treatment. Correctable risk factors should be addressed to minimize the number of risk factors present. The treatment of pITP must be individualized, including consideration of age-related disorders. |
| 5. | Spectrum of Factor VIII Gene Variants in 78 Patients with Hemophilia A in Guangxi Province, China, Including Nine Novel Variants: A Descriptive Study Jiali Jiang, Jinxia Jiang, Yuping Li, Lifang Huang, Hongying Wei doi: 10.4274/tjh.galenos.2025.2024.0418 Pages 299 - 305 Objective: Hemophilia A (HA) is an X-linked hereditary bleeding disorder caused by variants in the coagulation factor VIII (F8) gene, with a current estimated prevalence of 17.1 per 100,000 male individuals. This study aimed to establish a gene variant spectrum in China using long-distance polymerase chain reaction (PCR) and nextgeneration sequencing. Materials and Methods: Long-distance PCR was used to detect intron inversions and next-generation sequencing gene panels were used to identify small sequence variants. Results: Fifty-two different F8 variants were identified in 78 patients from unrelated families, including single-nucleotide alterations (missense, nonsense), frameshifts (small deletions/insertions), splicingsite changes, complex variations, and large rearrangements (inv22 or inv1). The nine variants reported here for the first time include two missense variants, two nonsense variants, four frameshifts, and one splicing alteration. Conclusion: The F8 gene mutation spectrum of patients with HA from Guangxi Province was established and genotype-phenotype correlations were explored. This study contributes data to the existing F8 mutation database and helps systematically identify the mutation spectrum of the gene for HA in southern China. |
| 6. | Evaluation of Immune Functions in Transfusion-Dependent Thalassemia Patients with Alloimmunization Nazli Özge Özköteş, Tuba Hilkay Karapınar, Sultan Okur Acar, Yüce Ayhan, Nesrin Gülez, Yeşim Oymak, Ferah Genel doi: 10.4274/tjh.galenos.2025.2025.0106 Pages 306 - 314 Objective: Regular erythrocyte suspension transfusions are still performed for most patients with beta-thalassemia major to prevent anemia. In recent years, it has been observed that patients are exposed to multiple allogeneic antigens and this leads to changes in the immune system. Understanding the immune regulators responsible for alloantibody development in thalassemia patients will provide appropriate data for the reduction and/or prevention of alloimmunization. We aimed to evaluate the association of alloimmunization and immune functions in these patients. Materials and Methods: Fifty-four patients with thalassemia between the ages of 1 and 24 years were retrospectively analyzed. The frequency and types of alloantibodies and the immune functions and demographic characteristics that affected their formation were examined in these patients. Results: The rate of alloantibody detection was 29.6%. There was a median interval of 13.7 years from the start of transfusions to alloantibody development. The age at initiation of regular transfusions was significantly higher in patients with alloantibody development. We found strong relationships between alloantibody development and both direct Coombs positivity and low C4+ and low CD19+ B-cell numbers. However, no significant difference was found between the groups in terms of serum immunoglobulin (Ig) G, IgA, IgM, and C3 levels; total lymphocyte count; or CD3+, CD4+, CD8+, and natural killer cell counts. Conclusion: Studies at the molecular level should be increased and research should be conducted with larger numbers of patients to clarify the immune pathogenesis of alloimmunization and determine the markers that will enable early recognition. |
| BRIEF REPORTS | |
| 7. | Real-World Clinical Outcomes and Prognostic Factors in Acquired Hemophilia A: A Single-Center Retrospective Analysis Selin Küçükyurt Kaya, Pelin Öztürk, Umut Yılmaz, Duygu Seyhan Erdoğan, Tuğrul Elverdi, Zafer Başlar, Muhlis Cem Ar doi: 10.4274/tjh.galenos.2025.2025.0201 Pages 315 - 319 Acquired hemophilia A (AHA) is a rare but potentially life-threatening bleeding disorder. This single-center retrospective study aimed to assess clinical features, treatment strategies, and prognostic indicators in adult AHA patients. Eleven patients diagnosed between 2008 and 2024 were reviewed. Clinical data, laboratory findings, treatments, and outcomes were analyzed. Survival estimates and prognostic factors were evaluated using Kaplan-Meier and univariate analyses. Median age was 41 years; 54.5% of the patients were female. Pregnancy-associated AHA (36.4%) had excellent outcomes with steroid monotherapy and no relapse. Idiopathic and autoimmune cases required combination therapy and had higher relapse rates. The median follow-up duration was 27 months. All patients achieved remission (median response time: 62 days), though 36.4% relapsed. High inhibitor titer (>20 Bethesda unit) predicted delayed response (p=0.038); male sex and major bleeding were linked to shorter relapse-free survival. Baseline inhibitor burden and disease etiology influence AHA prognosis. Tailored therapy and multicenter validation are warranted to refine management strategies. |
| IMAGES IN HEMATOLOGY | |
| 8. | Imatinib-Associated Hyperkeratotic Eruptions: A Rare Extensor Surface Manifestation Vishnu Sharma, Priyanshu Jain, Ayush Kulshreshtha doi: 10.4274/tjh.galenos.2025.2025.0055 Pages 320 - 321 Abstract | |
| 9. | The Cabot Ring at Different Stages of Erythropoiesis in the Bone Marrow of a Leukemic Patient Atakan Turgutkaya, Ayşe Hilal Eroğlu Küçükdiler, İrfan Yavaşoğlu doi: 10.4274/tjh.galenos.2025.2025.0086 Pages 322 - 323 Abstract | |
| LETTER TO THE EDITOR | |
| 10. | Engraftment Syndrome Following Autologous Stem Cell Transplantation in a Patient Receiving Nivolumab as Salvage Therapy Esra Terzi Demirsoy, Pınar Tarkun, Ayfer Gedük, Abdullah Hacıhanefioğlu, Özgür Mehtap doi: 10.4274/tjh.galenos.2025.2025.0166 Pages 324 - 326 Abstract | |
| 11. | Acute Myeloid Leukemia Post Cytotoxic Therapy with KMT2A Rearrangement Mimicking Acute Promyelocytic Leukemia Haiyang Wang, Jiulian Yuan, Ting Li, Hui Wang doi: 10.4274/tjh.galenos.2025.2025.0227 Pages 327 - 328 Abstract | |
| 12. | Diagnosing Myeloid Sarcoma from Peritoneal Fluid Ayşe Özkan Karagenç, Ali Ayçiçek, Esra Arslantaş, Nazlı Gülsüm Akyel, Özlem Başoğlu Öner doi: 10.4274/tjh.galenos.2025.2025.0156 Pages 329 - 330 Abstract | |
| 13. | A Rare Case of Hypocellular Acute Myeloid Leukemia: Clinical and Morphological Features Alper Koç, Hadice Akyol, Rafet Eren doi: 10.4274/tjh.galenos.2025.2025.0176 Pages 331 - 332 Abstract | |
| 14. | Extramedullary Hematopoiesis Causing Massive Pleural Effusion in a Chronic Lymphocytic Leukemia Patient: A Rare Case Rafiye Çiftçiler, Cem Selim, Ezgi Nur Aydın doi: 10.4274/tjh.galenos.2025.2025.0159 Pages 333 - 334 Abstract | |
| 15. | Inflammatory Bowel Disease or Drug-Induced Colitis? A Diagnostic Challenge in a CML Case with Dasatinib Therapy Hakan Demiröz, Yusuf Bünyamin Ketenci, Mehmet Akca, Mehmet Turgut, Ahmet Bektaş doi: 10.4274/tjh.galenos.2025.2025.0172 Pages 335 - 336 Abstract | |
| 16. | Defying the Odds: Successful Rescue with Teclistamab in a Case of Ultra-High-Risk Relapsed/Refractory Multiple Myeloma Transforming to Secondary Plasma Cell Leukemia Following BCMA CAR T Failure Bilal Kazi, Al-Ola A. Abdallah, Vijay Patil, Prashant Tembhare, Imaan Rumani, Marzooka Nazim Chishti Kazi doi: 10.4274/tjh.galenos.2025.2025.0216 Pages 337 - 341 Abstract | |
| 17. | A Case of VEXAS Syndrome Presenting with Unexplained Headache Ünal Ataş, Fadime Nurcan Alhan, Dilek Beypınar, Sevinç Şahin, Şakir Özgür Keşkek doi: 10.4274/tjh.galenos.2025.2025.0080 Pages 342 - 344 Abstract | |
| 18. | Successful Treatment with Romiplostim Following Eltrombopag- Induced Liver Injury in Primary Immune Thrombocytopenia Eren Arslan Davulcu doi: 10.4274/tjh.galenos.2025.2025.0209 Pages 345 - 347 Abstract | |
| 19. | Sitosterolemia with Compound Heterozygous Variants in the ABCG5 Gene: A Rare Cause of Non-Immune Hemolysis and Macrothrombocytopenia Başak Bostankolu Değirmenci, Hamza Polat doi: 10.4274/tjh.galenos.2025.2025.0093 Pages 348 - 349 Abstract | |
| INDEX | |
| 20. | Author Index Pages E1 - E5 Abstract | |
| 21. | Subject Index Pages E6 - E17 Abstract | |
| 22. | Advisory Board of This Issue Page E18 Abstract | |