British Journal of Haematology最新文献

{"title":"Addition of hydroxyurea (hydroxycarbamide) enhances the efficacy of fludarabine/cytarabine-based salvage regimens against acute myeloid leukaemia.","authors":"Ingrid Lilienthal, Sijia Tao, Christer Nilsson, Elory Leonard, Runqing Zhang, Agnes L Sorteberg, Louisa Fredrikson, Ioanna Xagoraris, Shahrzad Shirazi Fard, Nikolaos Tsesmetzis, Vasilios Zachariadis, Huan Cai, Lakshmi Sandhow, Anette Langebäck, Anna Bohlin, Katja Pokrovskaja Tamm, Sofia Bengtzén, Raymond F Schinazi, Sören Lehmann, Baek Kim, Georgios Z Rassidakis, Hong Qian, Martin Jädersten, Nikolas Herold","doi":"10.1111/bjh.70180","DOIUrl":"https://doi.org/10.1111/bjh.70180","url":null,"abstract":"<p><p>Despite intensive treatment, patients with relapsed or refractory acute myeloid leukaemia (AML) have a dismal prognosis. A cornerstone therapy for relapsed/refractory AML is a combination of fludarabine (F-ara-A) and cytarabine (ara-C), so-called FLA. As the enzyme SAMHD1 mediates resistance to both ara-C and F-ara-A, we investigated whether SAMHD1 inhibition via hydroxyurea (hydroxycarbamide; HU) could improve FLA efficacy. Here, we show that HU synergistically enhanced ara-C-, F-ara-A- and FLA-induced cytotoxicity in an SAMHD1-dependent manner in AML cell lines, primary AML cells and an immunocompetent AML mouse model. Mechanistically, HU significantly increased the active metabolite triphosphates of ara-C and F-ara-A in FLA combinations. Furthermore, leukaemic SAMHD1 protein expression negatively correlated with overall survival in a cohort of FLA-treated refractory AML patients. Our findings suggest that the addition of HU improves the efficacy of FLA-based regimens and warrant clinical trials to test the safety and efficacy of this combination in patients with relapsed/refractory AML.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equivalent incidences of paediatric graft-versus-host disease regardless of donor-recipient matching in the era of modern prophylaxis agents.","authors":"Sydney Ariagno, Jacob Greenmyer, Alexis Kuhn, Lindy Pence, Mary O'Shea, Lauren Greenmyer, Kristin Cole, Asmaa Ferdjallah, Mira Kohorst","doi":"10.1111/bjh.70184","DOIUrl":"https://doi.org/10.1111/bjh.70184","url":null,"abstract":"<p><p>Recipients of haploidentical and unrelated haematopoietic cell transplants (HCTs) historically had a higher risk for graft-versus-host disease (GvHD). However, with improved GvHD prophylaxis, recent data suggest adult patients undergoing transplantation from unrelated or mismatched donors now experience the rates of GvHD similar to those receiving matched related donor grafts. This finding is not yet explored in paediatric patients. The objectives of this study were to: (1) compare acute and chronic GvHD incidence, mortality and GvHD-free relapse-free survival (GRFS) among matched related donor (MRD), matched unrelated donor (MUD) and haploidentical paediatric HCT recipients in the era of enhanced GvHD prophylaxis for high-risk patients, (2) identify independent risk factors for GvHD and (3) evaluate the efficacy of various GvHD prophylactic regimens in our cohort. We conducted a retrospective, single-centre medical record abstraction among patients aged 0-25 years who underwent allogeneic HCT for any indication. The results demonstrated that 5-year cumulative incidence rates of any GvHD, all-cause mortality and GRFS are similar across the haploidentical, MRD and MUD groups. Tacrolimus-containing doublet/triplet regimens were associated with decreased GvHD, as compared to ciclosporin. Adding alemtuzumab also decreased risk for GvHD, without increasing relapse rates. Prospective studies with larger cohorts are warranted to further optimize outcomes for paediatric allogeneic HCT patients.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transformation and causes of death in follicular lymphoma: A Finnish nationwide population-based study.","authors":"Ilja Kalashnikov, Taina Reunamo, Tomas Tanskanen, Leevi Viisanen, Nea Malila, Sirkku Jyrkkiö, Sirpa Leppä","doi":"10.1111/bjh.70181","DOIUrl":"https://doi.org/10.1111/bjh.70181","url":null,"abstract":"<p><p>Follicular lymphoma (FL) is a common, indolent lymphoma, and patients with FL typically have a good prognosis. However, they may experience histological transformation into aggressive large B-cell lymphoma. We conducted a nationwide population-based study to estimate the risk of transformation in FL, considering different FL grades, and studied the relative survival (RS) of patients diagnosed with FL in Finland from 1995 to 2018. We identified a total of 4014 patients with newly diagnosed grade 1-3A FL. The median age at diagnosis was 64 years, and 55% of patients were female. The cumulative incidence of transformation across the entire cohort was 8.4% at 10 years (95% confidence interval [CI], 7.5-9.5). The 10-year RS was 78% for the whole cohort and showed improvement over time. Transformation was associated with a significantly increased risk of death (hazard ratio [HR] 5.0; 95% CI, 4.2-6.0; p < 0.001). Grade 3A was associated with higher excess mortality compared to patients with low-grade FL. Lymphoma was the most common cause of death. We conclude that, although the 10-year RS was relatively good, grade 3A FL and transformation led to significantly higher mortality compared to low-grade FL or no transformation. Our results also indicate a reduction in excess mortality over time.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treosulfan-fludarabine-based conditioning was associated with favourable event-free survival and very low risk of endothelial cell dysfunction in paediatric patients with non-malignant haematological disorders: Analysis of the UK Paediatric Treosulfan Study.","authors":"Daniel Farrugia, Robert Wynn, Katharine Patrick, Kanchan Rao, Geoff Shenton, Su Han Lum, Beki James","doi":"10.1111/bjh.70182","DOIUrl":"https://doi.org/10.1111/bjh.70182","url":null,"abstract":"","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The diagnostic performance of the basic versus the detailed telomere Flow FISH test in young patients with aplastic anaemia.","authors":"Nicholas F DeCleene, Duc T Nguyen, Susan E Kirk, Hannah L Helber, Ghadir S Sasa, Alison A Bertuch","doi":"10.1111/bjh.70155","DOIUrl":"https://doi.org/10.1111/bjh.70155","url":null,"abstract":"<p><p>Identifying telomere biology disorders (TBDs) in patients with aplastic anaemia (AA) is essential for guiding appropriate care. Telomere length (TL) measurement by flow cytometry with fluorescence in situ hybridization supports diagnosis, but the real-world performance of the basic test (lymphocytes and granulocytes) versus the detailed test (which includes four lymphocyte subsets) remains unclear. We retrospectively reviewed 439 patients who underwent detailed TL testing at our institution from 2008 to 2022. Haematological disease was present in 87%, with AA comprising 56%. We classified 23 subjects with TBD independently of TL, only one of whom had severe AA (SAA) at initial presentation. Granulocyte numbers were insufficient for TL analysis in 28% of subjects, precluding a rigorous assessment of the impact of granulocyte TL on identification of TBD. Very low TL in lymphocytes or ≥3 lymphocyte subsets identified all TBD cases across AA severity. However, positive predictive value (PPV) was low, particularly in SAA. The detailed test had greater specificity and PPV, particularly in mild AA, which had the greatest proportion of TBD cases among those with AA, supporting its use. However, additional diagnostics, such as genetic testing, remain necessary in many cases to confirm TBD and avoid misclassification.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MECOM fusion partner and bone marrow blast percentage influence outcomes of patients with MECOM rearranged acute myeloid leukaemia.","authors":"Wei-Ying Jen, Guilin Tang, Eitan Kugler, Jennifer Croden, Koji Sasaki, Alexandre Bazinet, Alex Bataller, Guillermo Montalban-Bravo, Gautam Borthakur, Gokce A Toruner, Sanam Loghavi, Nicholas J Short, Ghayas C Issa, Ian M Bouligny, Sherry Pierce, Uday Popat, Naveen Pemmaraju, Elias Jabbour, Guillermo Garcia-Manero, Kapil Bhalla, Farhad Ravandi, Naval G Daver, Courtney D DiNardo, Hagop M Kantarjian, Tapan M Kadia","doi":"10.1111/bjh.70171","DOIUrl":"10.1111/bjh.70171","url":null,"abstract":"<p><p>MECOM rearrangements (MECOM-r) are acute myeloid leukaemia (AML)-defining, regardless of blast percentage or MECOM fusion partner. We sought to investigate if blast percentage or MECOM-r partner was associated with overall survival (OS). We included 152 adult patients with newly diagnosed MECOM-r and classified blast percentage into <20% or ≥20% and MECOM-r partner into classic (GATA2::MECOM) or variant (others). Thirty-one per cent had <20% blasts, with 69% having ≥20%; 57% had classic and 43% variant MECOM-r. Treatment was with intensive chemotherapy (IC) in 41% and low-intensity therapy (LIT) in 59%. Composite complete remission rates were similar between IC (50%) and LIT (48%, p = 0.99). The median OS was 17 months (95% confidence interval [CI], 12-not estimable [NE]) for <20% blasts, compared with 9 months (95% CI, 6-10) for ≥20% blasts (p < 0.01). On multivariate analysis, ≥20% blasts were associated with worse OS (hazard ratio [HR] 1.9, [95% CI, 1.2-3.2], p < 0.01), independent of age, MECOM-r partner, additional cytogenetic abnormalities, treatment intensity, addition of venetoclax and stem cell transplant (SCT). HR for IC was 2.0 (95% CI, 1.1-3.7, p = 0.03). In <20% blasts, variant MECOM-r was independently associated with a reduced hazard of death (HR 0.2 [95% CI, 0.1-0.8], p < 0.01). MECOM-r AML is a heterogenous entity; consideration should be given to LIT approaches.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic haematopoietic cell transplantation in advanced systemic mastocytosis in new era: A CIBMTR study.","authors":"Celalettin Ustun, Mei-Jie Zhang, Andrew Peterson, Alexander Baek, Mounzer Agha, Hassan Alkhateeb, Saurabh Chhabra, Alex Coltoff, Marcos de Lima, Arpita Gandhi, Vincent Ho, Adetola Kassim, Adam Lin, Lohith Gowda, Gautam Borthakur, Daniel J DeAngelo, Joseph McGuirk, Felix Mensah, Kalyan V Nadiminti, Taiga Nishihori, Jeremy Pantin, Andrew Trunk, Joseph Uberti, Guido Marcucci, Jason Gotlib, Cem Akin, Mehdi Hamadani, Vinod Pullarkat, Peter Valent, Michael Grunwald, Mark Juckett, Betul Oran, Wael Saber, Linda J Burns","doi":"10.1111/bjh.70154","DOIUrl":"10.1111/bjh.70154","url":null,"abstract":"<p><p>We investigated the outcomes of patients with advanced systemic mastocytosis (AdvSM) undergoing allogeneic haematopoietic cell therapy (alloHCT) in the US. Twenty-seven adult (median age, 58 years) patients with AdvSM received alloHCT from 2014 to 2021. Most patients were white (93%), male (63%) and had systemic mastocytosis (SM) with associated haematological neoplasm (SM-AHN, 70%), received peripheral blood grafts (89%) and non-myeloablative regimens. KIT mutation was detected in 14 of the reported 16 patients (87.5%). Post-transplantation cyclophosphamide (PTCy) was used in approximately 50% of the cohort. Approximately 1 year after alloHCT, median bone marrow mast cell burden decreased from 15% pre-alloHCT to 1.5% (range 0-8) at 1 year post-alloHCT. The median serum tryptase decreased from 55 ng/mL (range 3-400 ng/mL) pre-alloHCT to 18 ng/mL (range 0-481 ng/mL) at 1 year post-alloHCT. At 1 year, progression-free survival (PFS) and overall survival (OS) were 59% (95% confidence interval [CI], 41%-77%) and 74% (95% CI, 56%-89%) respectively. In the subset of patients with SM-AHN, 1-year PFS and OS were 74% (52%-91%) and 79% (95% CI, 58%-94%) respectively. The cumulative incidence of relapse/progression for the entire population of patients with SM (n = 27) was 4% (95% CI, 0-14) at 100 days and 15% (95% CI, 4-31) at 1 year. For the subset of patients with AHN, the cumulative incidence was 11% (95% CI, 1-28) at 100 days and 21% (95% CI, 6-42) at 1 year. Relapse/progression was the cause of death in six of 12 patients (5 died of AHN and 1 died of SM progression). Eighteen and nine patients received a KIT inhibitor before alloHCT and after alloHCT respectively. In addition, six patients received a KIT inhibitor for the treatment of relapse/progression of SM after alloHCT. Although it is difficult to delineate the exact effect of alloHCT and KIT inhibitors because of the size of the study in this era, the use of alloHCT and KIT inhibitors pre- and post- alloHCT is increasing. In the near future, larger studies are required to provide further insights into this subject.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic dysregulation and therapeutic targeting of RET receptor tyrosine kinase in high-risk KMT2A-rearranged acute myeloid leukaemia.","authors":"Arundhati Chavan, Brendan Frett, Daniel T Armstrong, Baku Acharya, Pamela Lockyer, Marjan Boerma, Samrat Roy Choudhury","doi":"10.1111/bjh.70183","DOIUrl":"https://doi.org/10.1111/bjh.70183","url":null,"abstract":"","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loncastuximab tesirine elicits complete responses in secondary central nervous system lymphoma.","authors":"Adam J Olszewski, Diana O Treaba, Allison Winter, Stephen Donnelly, Thomas A Ollila","doi":"10.1111/bjh.70178","DOIUrl":"https://doi.org/10.1111/bjh.70178","url":null,"abstract":"","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The epidemiological landscape of bloodstream infections in children undergoing chemotherapy or haematopoietic cell transplantation: A retrospective study by Infectious Diseases Working Group of Italian Association of Pediatric Hematology and Oncology (AIEOP).","authors":"Francesco Baccelli, Francesca Compagno, Gloria Tridello, Francesco Delle Cave, Daniele Zama, Riccardo Masetti, Maria Grazia Petris, Lorenzo Chiusaroli, Manuela Spadea, Francesca Trevisan, Antonella Colombini, Samantha Conci, Cristina Meazza, Paola Muggeo, Maria Vittoria Micheletti, Alessia Pancaldi, Rosamaria Mura, Daniela Onofrillo, Raffaella De Santis, Milena La Spina, Elio Castagnola, Katia Perruccio, Angelica Barone, Nagua Giurici, Angelamaria Petrone, Federico Mercolini, Simona Rinieri, Simone Cesaro","doi":"10.1111/bjh.70036","DOIUrl":"https://doi.org/10.1111/bjh.70036","url":null,"abstract":"<p><p>Understanding bloodstream infection (BSI) epidemiology is crucial for optimizing antibiotic therapy in paediatric haematology-oncology patients undergoing chemotherapy or haematopoietic cell transplantation (HCT). However, updated paediatric data remain scarce. This multicentre retrospective study analysed BSI epidemiology across 22 Italian centres (2018-2019), assessing pathogens, resistance profiles, empirical antibiotic therapy (EAT) and clinical course with outcomes. Mortality risk factors were evaluated using a Cox regression model. A total of 510 BSI episodes occurred in 396 patients (median age 6.4 years), with an incidence of 2.9 and 5.1 per 1000 inpatient days for chemotherapy and HCT respectively. Multidrug-resistant (MDR), third to fourth generation cephalosporin- and carbapenem-resistant, account for 18.3%, 29.3% and 8.2% of Gram-negative infections respectively. 42.2% of Klebsiella pneumoniae isolates were MDR. Combination EAT was used in 269/510 episodes, with piperacillin-tazobactam+amikacin being most common. Microbiological appropriateness was 82%. Infection-related and 30-day mortality rates were 4.1% and 5.29%, respectively, with appropriate EAT significantly reducing mortality. Our findings highlight the burden of resistant pathogens in paediatric BSIs and emphasize the importance of appropriate EAT in improving outcomes, underscoring the need for treatment strategies tailored to local resistance patterns.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}