Annals of Hematology最新文献

{"title":"Radiotherapy alone with curative intent in a case of limited-stage extranodal NK/T-cell lymphoma nasal type: a case report and review of the literature.","authors":"Biancamaria Mandelli, Donatella Caivano, Antonella Fontana, Natalia Cenfra, Sergio Mecarocci, Maristella Marrocco, David Fanciullo, Roberta Mazzarella, Martina Lorenzon, Giada Pacitto, Alessandro Pulsoni","doi":"10.1007/s00277-025-06260-x","DOIUrl":"10.1007/s00277-025-06260-x","url":null,"abstract":"<p><p>Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT), is an aggressive malignancy primarily affecting the sinonasal region, with a strong association with Epstein-Barr virus (EBV) infection. The disease is significantly more prevalent in Asian and Latin American populations. Diagnosis is particularly challenging in nonendemic regions. We present the case of a 78-year-old male with a one-year history of nasal lesions, later diagnosed with ENKTCL-NT. The patient was treated with curative-intent radiotherapy, achieving a complete clinical response. Radiation therapy, particularly utilizing advanced techniques such as Volumetric Modulated Arc Therapy (VMAT), resulted in favorable outcomes with minimal toxicity. This case emphasizes the importance of early diagnosis, accurate staging, and personalized radiotherapy in the management of ENKTCL-NT. Ongoing research into the molecular pathogenesis, treatment strategies, and prognostic factors is crucial for improving outcomes, particularly in advanced-stage disease.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"3001-3006"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase-1 study of vamotinib (PF-114), a 3rd generation BCR::ABL1 tyrosine kinase-inhibitor, in chronic myeloid leukaemia.","authors":"Anna Turkina, Olga Vinogradova, Elza Lomaia, Evgeniya Shatokhina, Oleg Shukhov, Ekaterina Chelysheva, Dzhariyat Shikhbabaeva, Irina Nemchenko, Anna Petrova, Anastasiya Bykova, Nadiya Siordiya, Vasily Shuvaev, Ilya Mikhailov, Fedor Novikov, Veronika Shulgina, Andreas Hochhaus, Oliver Ottmann, Jorge Cortes, Robert Peter Gale, Ghermes Chilov","doi":"10.1007/s00277-025-06239-8","DOIUrl":"10.1007/s00277-025-06239-8","url":null,"abstract":"<p><p>Vamotinib (PF-114) is a 3rd -generation, ATP-competitive oral tyrosine kinase inhibitor (TKI) active against wild-type and mutated BCR::ABL1 isoforms including BCR::ABL1^T315I. We present final results of a phase-1 vamotinib dose-escalation study to identify maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) followed by expansion cohorts. 51 subjects with chronic myeloid leukaemia (CML) failing ≥ 1 2nd generation TKI or with BCR::ABL1^T315I were enrolled. Subjects received vamotinib, 50-750 mg/d, continuously. Median exposure was 6 months (range, < 1-52 months). Median CML duration pre-study was 10 years (range, < 1-23 years). 27 subjects received ≥ 3 prior TKIs and 16 had BCR::ABL1^T315I. The MTD was 600 mg with the Grade-3 psoriasis-like skin toxicity as the DLT. There were no vascular occlusive events nor deviations of ankle-brachial index. Complete haematologic response (CHR) was achieved in 14 of 30 subjects, major cytogenetic response (MCyR) in 14 of 44 subjects, complete cytogenetic response (CCyR) in 10 of 50 and major molecular response (MMR) in 7 of 51 subjects who did not have a CHR, MCyR, CCyR or MMR at enrollment. The best safety/efficacy dose was 300 mg with MCyR achieved in 6 of 7 subjects, CCyR in 5 of 9 and MMR in 4 of 9 subjects who did not have a MCyR, CCyR or MMR at enrollment. 5 of 16 subjects with BCR::ABL1^T315I responded including 3 achieving a CHR, 3, a MCyR, and 1,a CCyR. 2 of 5 subjects failing ponatinib achieved a CHR. Vamotinib dose for further phase-3 study is 300 mg/d.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"2707-2715"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venous thromboembolic risk in hematological hospitalized patients: a retrospective study.","authors":"Stefano Cordella, Valeria Coluccio, Riccardo Cuoghi Costantini, Roberto D'Amico, Mario Luppi, Marco Marietta","doi":"10.1007/s00277-025-06397-9","DOIUrl":"10.1007/s00277-025-06397-9","url":null,"abstract":"<p><p>Although patients with hematological malignancies carry a non-negligible risk of venous thromboembolic events (VTE), no risk assessment models (RAMs) have been developed and validated to predict this risk during their hospital stay. Moreover, the performance of RAMs developed to predict the thromboembolic and hemorrhagic risk in hospitalized medical patients has never been assessed in this specific population. In this observational study we sought to assess the incidence of VTE and hemorrhagic events (HE), to evaluate pharmacological prophylaxis use, and to test existing RAMs for TE and HE (Padua Predictions Score, PPS, and Improve Bleeding Score, IBS, respectively) in a population of 514 hematological patients at their first hospital admission. 165 patients were found to be at high thromboembolic and 114 at high hemorrhagic risk according to PPS and IBS; a total of 148 patients received pharmacological prophylaxis with low-molecular weight heparin (LMWH). An incidence of VTE (3.11%) and HE (1.75%) was found, with most thrombotic (15/16) and hemorrhagic (8/9) events occurring in patients not receiving prophylaxis. At the univariate analysis, the diagnosis of acute leukemia was significantly associated with an increased risk of VTE, whereas prophylaxis was found to be protective. However, at the multivariate analysis the statistical significance was lost for both of these variables (HR = 2.76, p = 0.218 and HR = 0.22, p = 0.170, respectively). PPS poorly performed in this population, but no other factors associated with VTE were found. Larger, multicenter studies to develop better RAMs tailored to HM patients are needed to improve VTE management in this population.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"2963-2971"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular predictors of venous and arterial thrombotic events in patients with myelofibrosis.","authors":"Olga Morath, Jenny Rinke, Annabell Walter, Carl Crodel, Manja Meggendorfer, Constance Baer, Andreas Hochhaus, Thomas Ernst","doi":"10.1007/s00277-025-06361-7","DOIUrl":"10.1007/s00277-025-06361-7","url":null,"abstract":"<p><p>While patients with myelofibrosis (MF) face an elevated risk of thrombosis, no validated scoring system currently exists to effectively assess this specific risk. This study aimed to explore distinct molecular risk factors for arterial (ATE) and venous (VTE) thrombosis in a cohort of 141 MF patients. Mutation analysis was performed by next-generation sequencing for a panel of 30 target myeloid genes as previously described: 137 driver and 164 non-driver mutations were detected. JAK2-V617F was identified in 77 (55%) patients, CALR in 45 (32%) patients, and seven (5%) patients carried an MPL variant. Patients #58 and #60 harbored JAK2-V617F and MPL; and patient #67 was positive for all three driver genes. The JAK2-V617F variant allele frequency (VAF) was assessed in 66/80 patients, revealing a median of 34.0% (range, 5.0-96.0). ASXL1 (n = 34 patients) were the most common non-driver mutations, followed by TET2 (n = 26), U2AF1 (n = 12), and DNMT3A (n = 11). During a median follow up of 4.8 years, 24 (17%) patients experienced VTE, 15 (11%) ATE, and two patients experienced both. Among the 24 patients with VTE, 12 (50%) experienced splanchnic vein thrombosis. The JAK2-V617F mutation was associated with VTE (OR 2.6, 95% CI 1.01-7.16), while the DNMT3A mutation was an independent predictor of ATE (OR 5.40, 95% CI 1.30-22.42). High JAK2-V617F VAF (> 50%) was not related with an increased thrombotic risk. Results of this study demonstrate the significance of DNMT3A mutations as an independent molecular risk factor for ATE, highlighting the potential to include these somatic non-driver mutations in future thrombosis risk scores.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"2755-2763"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of graft-versus-host disease on outcomes of cord blood transplantation according to HLA disparity and its prophylaxis type.","authors":"Hisayuki Yokoyama, Shigeo Fuji, Makoto Murata, Masahiro Hirayama, Atsushi Wake, Naoyuki Uchida, Masatsugu Tanaka, Makoto Onizuka, Satoshi Takahashi, Noriko Doki, Yumiko Maruyama, Kazuya Ishiwata, Yasufumi Uehara, Tetsuya Nishida, Masashi Sawa, Toshiro Kawakita, Tetsuya Eto, Fumihiko Ishimaru, Koji Kato, Tatsuo Ichinohe, Yoshiko Atsuta, Seitaro Terakura, Satoko Morishima","doi":"10.1007/s00277-025-06415-w","DOIUrl":"10.1007/s00277-025-06415-w","url":null,"abstract":"<p><p>This study evaluated the impact of acute graft-versus-host disease (aGVHD) on cord blood transplantation (CBT) outcomes based on human leukocyte antigen (HLA) disparity and GVHD prophylaxis type. Data from 4,196 adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome were analyzed. Patients were classified by HLA mismatch (8/8-6/8, 5/8, and 4/8-2/8) and further by GVHD prophylaxis type (methotrexate [MTX] or mycophenolate mofetil [MMF]). The impact of aGVHD was assessed using a time-dependent Cox model. Grade I-II aGVHD improved overall survival (OS) in all groups, regardless of HLA mismatches or prophylaxis type. However, grade III-IV aGVHD worsened OS across MMF groups, while in MTX groups, it was unfavorable only in the HLA 8/8-6/8-matched group (HR 1.6, P = 0.01). Grade III-IV aGVHD increased non-relapse mortality (NRM) across all groups but was more pronounced in HLA 4/8-2/8-matched patients receiving MMF. Notably, relapse risk decreased in HLA 4/8-2/8-matched patients with MTX prophylaxis, partially offsetting the negative impact of grade III-IV aGVHD on NRM. These findings suggest that the impact of aGVHD varies with HLA mismatches and prophylaxis type. MTX prophylaxis may mitigate the adverse effects of severe aGVHD in highly mismatched cases, unlike MMF prophylaxis. Careful donor selection considering HLA mismatches is essential when using MMF prophylaxis to manage severe aGVHD and reduce NRM risk.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"2905-2913"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet-to-Neutrophil ratio as a predictor of risk of complications in sickle cell disease: a valuable insight for resource-limited settings.","authors":"Chilota Efobi, Nnanna Ukpai, Onyinye Ezinne Eze, Bruno Basil","doi":"10.1007/s00277-025-06419-6","DOIUrl":"10.1007/s00277-025-06419-6","url":null,"abstract":"<p><p>Sickle cell disease (SCD) presents significant clinical challenges, particularly in resource-limited settings where early identification of high-risk patients remains difficult, necessitating the use of simple, cost-effective biomarkers to improve risk stratification and guide timely interventions. This study investigates the potential of platelet-to-neutrophil ratio (PNR) to serve as a predictor for risk of specific SCD complications in a population of Nigerian patients. This hospital-based cross-sectional analytical study was conducted over 7 months and included a total of 73 adult patients with haemoglobin SS genotype in a steady state. Data on socio-demographics, medical history, clinical characteristics, and laboratory parameters, including platelet-to-neutrophil ratio (PNR) were obtained. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 25. Comparative statistical analyses, binary logistic regression, and receiver operating characteristic (ROC) curve evaluations were performed to determine the predictive value of PNR for risk of SCD complications. Patients with avascular necrosis (AVN) had significantly lower median PNR values compared to those without the condition (151.0 IQR: 311.2 vs. 77.5 IQR: 61.0, p = 0.004). Multivariate logistic regression analysis identified PNR as an independent predictor of AVN (p = 0.034, OR = 1.003, 95% CI: 1.000-1.006), with an ROC-derived optimal cutoff of 96.6 yielding a sensitivity of 69.6% and specificity of 76.5% (AUC = 0.733, p = 0.004). This study reveals that RNR demonstrates reasonable potential as a predictor of AVN in Nigerian SCD patients and could serve as an easily accessible biomarker for SCD risk stratification, particularly in resource-limited settings. Further studies are needed for validation of its clinical utility and possible integration into SCD management protocols.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"2663-2669"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and risk factors of severe infections in diffuse large B-cell lymphoma patients undergoing immunochemotherapy.","authors":"Haiqiu Zhao, Rong Su, Jie Luo, Lin Liu","doi":"10.1007/s00277-025-06296-z","DOIUrl":"10.1007/s00277-025-06296-z","url":null,"abstract":"<p><p>To determine the incidence and risk factors of severe infection (SI) in patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab-chemotherapy (R-C). This retrospective study was conducted at a tertiary care center in China. Patients with newly diagnosed DLBCL who were treated with R-C between January 1, 2022, and July 1, 2023, at our center were included in this study. SI was defined as an infection resulting in hospitalization. COVID-19 infections were excluded from the study. Patients were categorized as having SI or not by analyzing clinical data, comparing the characteristics of the two groups, and exploring the independent risk factors for SI using multivariate logistic analyses. A total of 300 patients were enrolled in this study, with a male-to-female ratio of 1:1.03 and a median age of 62 years (range: 20-88 years). A total of 117 patients (39.0%) developed SIs, with most (86.3%) occurring within six months of the first treatment. One-third of the infections were identified as opportunistic. Advanced stage disease (OR 2.814, 95% CI 1.603-4.939, P < 0.001), smoking history (OR 9.379, 95% CI 3.901-22.547, P < 0.001), concomitant autoimmune diseases (OR 3.730, 95% CI 1.349-10.311, P = 0.011), dexamethasone equivalent dose ≥ 15 mg/d (OR 2.436, 95% CI 1.213-4.894, P = 0.012) and prophylactic treatment with granulocyte-stimulating factors (OR 0.319, 95% CI 0.178-0.574, P < 0.001) were independently associated with the development of SI in DLBCL patients receiving R-C. Infection is a relatively common complication following R-C treatment in patients with DLBCL. Independent risk factors for SI were identified, which may aid clinicians in developing individualized infection prevention and treatment strategies.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"2869-2879"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world data on the use of subcutaneous daratumumab plus bortezomib, thalidomide, and dexamethasone in transplant-eligible patients with newly diagnosed multiple myeloma.","authors":"Vania Hungria, Fernanda Lemos Moura, Abel Costa, Eduardo Flávio Oliveira Ribeiro, Paulo Soares, Juliana Souza Lima, Lisa Aquaroni Ricci, Celso Arrais-Rodrigues, Fabio Moore Nucci, Marinus de Moraes Lima, Roberto Jose Pessoa de Magalhães Filho, Amitabha Bhaumik, Trilok Parekh, Fredrik Borgsten, Robin Carson, Damila C Trufelli, Edvan de Queiroz Crusoe","doi":"10.1007/s00277-025-06365-3","DOIUrl":"10.1007/s00277-025-06365-3","url":null,"abstract":"<p><p>Subcutaneous daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd), is approved for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). However, additional real-world data are needed to assess the effectiveness and safety of D-VTd in routine clinical practice. We conducted a noninterventional, multicenter, observational study across hematology centers in Brazil to gather real-world data on D-VTd in patients with NDMM who were eligible for autologous stem cell transplant (ASCT). Eligible patients must have completed 1 or more cycle of D-VTd, on or before September 30, 2022, to be included. Data were collected retrospectively from the start of D-VTd to the study inclusion visit using patient medical records and prospectively thereafter using electronic case report forms. As of the data cutoff (August 8, 2023), 49 patients were included. By the end of consolidation, 91.7% of patients achieved an overall response (partial response or better) and 89.6% achieved very good partial response or better. Forty-five (91.8%) patients underwent stem cell mobilization with a median stem cell yield of 5.7 × 10⁶ CD34+ cells/kg, and 44 (89.8%) patients underwent ASCT, among whom 43 out of 44 (97.7%) successfully completed ASCT. D-VTd was well tolerated, with a safety profile consistent with that previously known for daratumumab and VTd. Grade 3/4 neutropenia/febrile neutropenia and infections were reported in 32.7% and 18.4% of patients, respectively. Overall, results were consistent with the established profile of D-VTd, and these real-world effectiveness and safety results support the frontline use of subcutaneous daratumumab plus VTd in transplant-eligible patients with NDMM.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"2787-2798"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical usefulness of next-generation sequencing-based target gene sequencing in diagnosis of inherited bone marrow failure syndrome.","authors":"Young Dai Kwon, Kyung Taek Hong, Juyeon Lee, Yoon Sunwoo, Yeseul Kim, Sung Im Cho, Hyun Jin Park, Bo Kyung Kim, Jee-Soo Lee, Jung Yoon Choi, Moon-Woo Seong, Hyoung Jin Kang","doi":"10.1007/s00277-025-06392-0","DOIUrl":"10.1007/s00277-025-06392-0","url":null,"abstract":"<p><p>Inherited bone marrow failure syndromes are genetic hematologic disorders with increased cancer risk. Accurate diagnosis is crucial for appropriate management. This study assessed the clinical usefulness of next-generation sequencing (NGS)-based target gene sequencing in pediatric and AYA (adolescent and young adult) patients with hematologic abnormalities. From December 2019 to June 2023, 93 patients with suspected congenital hematologic diseases at a single institution underwent NGS-based testing. Medical records were retrospectively reviewed. The median age at diagnosis was 9.3 years (range 0.2-31.4), with 59.1% males. Indications for testing included specific medical histories (28 patients), persistent cytopenia or recurrent neutropenic fever (22 patients), changes in cytopenia patterns (11 patients), and other reasons (32 patients). Pathogenic variants were identified in 9/28 (32.1%), 3/22 (13.6%), 4/11 (36.4%), and 0/32 (0%). Overall, 16 patients (17.2%) had pathogenic variants, including FANCA, BRCA2, PMS2, ELANE, G6PC3 and VPS13B in patients with idiopathic neutropenia, and GATA2 in patients with suspected myelodysplastic syndrome. Genetic findings led to diagnostic revisions in 12 patients (12.9%), including reclassification of aplastic anemia (AA) as Fanconi anemia, Diamond-Blackfan anemia, or Shwachman-Diamond syndrome, prompting hematopoietic stem cell transplantation and altering cancer surveillance. Pathogenic variants were more frequently observed in patients with a specific medical history or changes in cytopenia, and in those with additional clinical features (cytogenetic abnormalities or non-severe AA). This study demonstrated the diagnostic usefulness of NGS-based target gene sequencing for pediatric and AYA patients with suspected genetic hematologic disorders, supporting the need for multicenter studies and standardized guideline development.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"2693-2706"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic polymorphism of novel SNP rs5006884 in OR51B6 and SNP rs4499252 in AHSP among transfusion-dependent and non-transfusion-dependent β-thalassemia/Hb E patients in Thailand: a multivariate analysis of clinical and genetic polymorphism.","authors":"Chidchanok Mahabhol, Lalana Yothindamrongkul, Nicha Nuntanajaroenkul, Purima Nawasod, Wanicha Tepakhan, Rossarin Karnpean, Panjarat Sowithayasakul, Nisa Makruasi, Therdkiat Trongwongsa, Wittaya Jomoui","doi":"10.1007/s00277-025-06403-0","DOIUrl":"10.1007/s00277-025-06403-0","url":null,"abstract":"<p><p>Compound heterozygous β-thalassemia and Hb E, a prevalent and severe form of thalassemia in Southeast Asia, manifests in two major clinical forms: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). This study investigates the association of genetic polymorphisms rs5006884 in OR51B6, rs4499252 in AHSP, rs9399137 in HBS1L-MYB, and rs4671393 in BCL11A with clinical severity and transfusion dependency in β-thalassemia/Hb E patients in Thailand. A total of 189 samples, including 58 TDT, 58 NTDT, 33 homozygous Hb E, and 40 wild-type individuals, were analyzed. Genotyping of the four single nucleotide polymorphisms (SNPs) was conducted using the rhAmp SNP Genotyping assay. Multivariate regression models were developed to evaluate the combined effects of genetic and clinical factors on transfusion dependency. The results showed that OR51B6 SNP rs5006884 TT genotype was significantly more frequent in the NTDT group (P < 0.05), suggesting a strong association with reduced transfusion dependency. Conversely, the AHSP SNP rs4499252 GG genotype was significantly less frequent in the homozygous Hb E group (P < 0.05) compared to other groups. Multivariate analyses highlighted hemoglobin (Hb) levels as a robust predictor of transfusion dependency, with specific HBB mutations including HBB:c.59 A > G, HBB:c.-78 A > G, HBB:c.316-197 C > T, and NC_000011.10:g.5224302_5227791del being significantly associated with NTDT (P < 0.05). Furthermore, rs5006884 in OR51B6 also played a significant role in NTDT in multivariate analyses. In contrast, SNPs in BCL11A (rs4671393), HBS1L-MYB (rs9399137), and AHSP (rs4499252) showed no significant independent associations with transfusion dependency or disease severity in this cohort. This study explores rs5006884 in OR51B6 and rs4499252 in AHSP in TDT and NTDT patients for the first time. These findings elucidate the interplay of genetic and clinical factors influencing β-thalassemia severity, paving the way for personalized management strategies to mitigate transfusion requirements.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":"2653-2661"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}