Pub Date : 2026-02-03DOI: 10.1016/S2352-3026(25)00328-X
Valentín Ortiz-Maldonado, Núria Martínez-Cibrian, Leticia Alserawan, Marta Español-Rego, Sergio Navarro-Velázquez, Nil Albiol, Aina Oliver-Caldés, Ana Triguero, María Herrero-García, Sara Gutiérrez-Herrero, Daniel Benítez-Ribas, María Liz Paciello, Anna Torrent, Javier Delgado-Serrano, María Sánchez-Castañón, Hugo Calderón, Juan José Mata, Andrés Sánchez-Salinas, Joaquín Sáez-Peñataro, Carla Sans-Pola, Maria Calvo-Orteu, Lucía López-Corral, Mi Kwon, José Rifón, Paola Charry, Rafael Alberto Alonso-Fernández, María Huguet, Cristina Blázquez-Goñi, José María Sánchez-Pina, Ricardo Sánchez, Juan Manuel Rosa-Rosa, Joaquín Martínez-López, Miguel Blanquer, Josep Maria Ribera, Álvaro Urbano-Ispizua, Mireia Bachiller, Laura Palau, Eulalia Olesti, Gonzalo Calvo, Lourdes Martín-Martín, Alberto Orfao, E Azucena González-Navarro, Gemma Domenech, Sara Varea, Manel Juan, Julio Delgado, Jordi Esteve
<p><strong>Background: </strong>Varnimcabtagene autoleucel (var-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy with adaptive intra-patient dose escalation and was approved in Spain in 2021 for patients older than 25 years with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia. We report activity and safety from var-cel's pivotal trial in this patient population.</p><p><strong>Methods: </strong>This multicentre, single-arm, phase 2 trial was conducted at nine academic centres in Spain. Eligible patients had CD19<sup>+</sup> B-cell precursor acute lymphoblastic leukaemia in the first relapse or refractory disease, either ineligible for allogeneic haematopoietic cell transplantation (HCT) or with relapsed disease after allogeneic HCT; centralised measurable disease in peripheral blood or bone marrow, or both, using flow cytometry; were aged 18-70 years; and had an Eastern Cooperative Oncology Group performance status of 0-2. Patients received a single course of intravenous lymphodepleting chemotherapy with fludarabine (30 mg/m<sup>2</sup> per day for 3 days) plus cyclophosphamide (300 mg/m<sup>2</sup> per day for 3 days), followed by intravenous fractionated var-cel escalation (0·1, 0·3, 0·6, and 2·0 × 10<sup>6</sup> CAR T cells per kg) separated by at least 24 h, with each fraction contingent on safety criteria. The primary endpoint was complete response with undetected measurable residual disease (MRD; sensitivity of ≤10<sup>-5</sup>) determined by flow cytometry by day 28 from var-cel administration, assessed in the efficacy population (defined as all patients who received at least one var-cel fraction). Safety was analysed in patients that initiated lymphodepletion. This study is registered with ClinicalTrials.gov, NCT04778579 (completed).</p><p><strong>Findings: </strong>Between May 19, 2021, and July 6, 2023, 50 patients were assessed for eligibility, 12 were ineligible, and 38 were enrolled. 37 (97%) of 38 underwent leukapheresis (ITT population), 33 (87%) initiated lymphodepleting chemotherapy (safety population), and 32 (84%) received at least one var-cel fraction (efficacy population). Five patients who underwent leukapheresis did not receive var-cel due to rapid disease progression (n=3), death due to veno-oclusive disease (n=1), and persistent COVID-19 (n=1). Patients receiving var-cel had a median age of 40 years (33-48); of whom, 16 (50%) were female and 16 (50%) were male. By data cutoff (Jan 18, 2024), the median follow-up from infusion was 8·6 months (IQR 5·1-14·4) and 27 (84·4% [95% CI 67·2-94·7]) of 32 patients who received at least one dose of var-cel had a complete response with undetected MRD by day 28. Treatment-emergent adverse events occurred in 31 (94%) of 33 patients. The most common grade 3 or higher adverse events were neutropenia in 15 (45%) patients, thrombocytopenia in seven (21%), anaemia in five (15%), and cytokine release syndrome in four (12%). Immune effecto
{"title":"Varnimcabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia in Spain (CART19-BE-02): a multicentre, single-arm, phase 2 trial.","authors":"Valentín Ortiz-Maldonado, Núria Martínez-Cibrian, Leticia Alserawan, Marta Español-Rego, Sergio Navarro-Velázquez, Nil Albiol, Aina Oliver-Caldés, Ana Triguero, María Herrero-García, Sara Gutiérrez-Herrero, Daniel Benítez-Ribas, María Liz Paciello, Anna Torrent, Javier Delgado-Serrano, María Sánchez-Castañón, Hugo Calderón, Juan José Mata, Andrés Sánchez-Salinas, Joaquín Sáez-Peñataro, Carla Sans-Pola, Maria Calvo-Orteu, Lucía López-Corral, Mi Kwon, José Rifón, Paola Charry, Rafael Alberto Alonso-Fernández, María Huguet, Cristina Blázquez-Goñi, José María Sánchez-Pina, Ricardo Sánchez, Juan Manuel Rosa-Rosa, Joaquín Martínez-López, Miguel Blanquer, Josep Maria Ribera, Álvaro Urbano-Ispizua, Mireia Bachiller, Laura Palau, Eulalia Olesti, Gonzalo Calvo, Lourdes Martín-Martín, Alberto Orfao, E Azucena González-Navarro, Gemma Domenech, Sara Varea, Manel Juan, Julio Delgado, Jordi Esteve","doi":"10.1016/S2352-3026(25)00328-X","DOIUrl":"https://doi.org/10.1016/S2352-3026(25)00328-X","url":null,"abstract":"<p><strong>Background: </strong>Varnimcabtagene autoleucel (var-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy with adaptive intra-patient dose escalation and was approved in Spain in 2021 for patients older than 25 years with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia. We report activity and safety from var-cel's pivotal trial in this patient population.</p><p><strong>Methods: </strong>This multicentre, single-arm, phase 2 trial was conducted at nine academic centres in Spain. Eligible patients had CD19<sup>+</sup> B-cell precursor acute lymphoblastic leukaemia in the first relapse or refractory disease, either ineligible for allogeneic haematopoietic cell transplantation (HCT) or with relapsed disease after allogeneic HCT; centralised measurable disease in peripheral blood or bone marrow, or both, using flow cytometry; were aged 18-70 years; and had an Eastern Cooperative Oncology Group performance status of 0-2. Patients received a single course of intravenous lymphodepleting chemotherapy with fludarabine (30 mg/m<sup>2</sup> per day for 3 days) plus cyclophosphamide (300 mg/m<sup>2</sup> per day for 3 days), followed by intravenous fractionated var-cel escalation (0·1, 0·3, 0·6, and 2·0 × 10<sup>6</sup> CAR T cells per kg) separated by at least 24 h, with each fraction contingent on safety criteria. The primary endpoint was complete response with undetected measurable residual disease (MRD; sensitivity of ≤10<sup>-5</sup>) determined by flow cytometry by day 28 from var-cel administration, assessed in the efficacy population (defined as all patients who received at least one var-cel fraction). Safety was analysed in patients that initiated lymphodepletion. This study is registered with ClinicalTrials.gov, NCT04778579 (completed).</p><p><strong>Findings: </strong>Between May 19, 2021, and July 6, 2023, 50 patients were assessed for eligibility, 12 were ineligible, and 38 were enrolled. 37 (97%) of 38 underwent leukapheresis (ITT population), 33 (87%) initiated lymphodepleting chemotherapy (safety population), and 32 (84%) received at least one var-cel fraction (efficacy population). Five patients who underwent leukapheresis did not receive var-cel due to rapid disease progression (n=3), death due to veno-oclusive disease (n=1), and persistent COVID-19 (n=1). Patients receiving var-cel had a median age of 40 years (33-48); of whom, 16 (50%) were female and 16 (50%) were male. By data cutoff (Jan 18, 2024), the median follow-up from infusion was 8·6 months (IQR 5·1-14·4) and 27 (84·4% [95% CI 67·2-94·7]) of 32 patients who received at least one dose of var-cel had a complete response with undetected MRD by day 28. Treatment-emergent adverse events occurred in 31 (94%) of 33 patients. The most common grade 3 or higher adverse events were neutropenia in 15 (45%) patients, thrombocytopenia in seven (21%), anaemia in five (15%), and cytokine release syndrome in four (12%). Immune effecto","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":17.7,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/S2352-3026(25)00322-9
Rudolf Stadler, Pietro Quaglino, F J Sherida H Woei-A-Jin, Reinhard Dummer, Christina Mitteldorf, Evangelia Papadavid, Pablo L Ortiz Romero, Emmanuella Guenova, Riichiro Abe, Richard Cowan, Martine Bagot, Stéphane Dalle, Taku Fujimura, Thilo Gambichler, Stephen Morris, Ulrike Wehkamp, Patrick Terheyden, Antonio Cozzio, Edgar Dippel, Silvia Alberti-Violetti, Joanna Romejko-Jarosinska, Anna Wozniacka, Eva González Barca, Ramon Pujol Vallverdu, Egle Ramelyte, Oliver Bechter, Kenta Suzuki, Robert Knobler, Susanne Danhauser-Riedl, Julia Scarisbrick
<p><strong>Background: </strong>In advanced-stage cutaneous T-cell lymphoma (CTCL), current therapeutic options rarely provide long-lasting responses. We aimed to evaluate the efficacy and safety of a histone deacetylase inhibitor, resminostat, as maintenance therapy in patients with advanced-stage mycosis fungoides or Sézary syndrome, in whom disease control had been previously met.</p><p><strong>Methods: </strong>We conducted a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial (RESMAIN) at 55 medical centres in Austria, Belgium, France, Germany, Greece, Italy, the Netherlands, Poland, Spain, Switzerland, the UK, and Japan. Adult patients (aged ≥18 years) with histologically confirmed, stage IIB-IVB mycosis fungoides or Sézary syndrome; an Eastern Cooperative Oncology Group performance status score of 0-2; and disease control after at least one previous systemic therapy or total skin electron beam were eligible for inclusion. Patients were randomly assigned to receive either oral resminostat (600 mg) or matching oral placebo once daily for 5 days, followed by a treatment-free period of 9 days, within a 14-day treatment cycle. Randomisation was stratified by disease stage (IIB-IVA1 vs IVA2-IVB) and remission status following previous therapy (complete or partial response vs stable disease) by use of a dynamic block allocation process (block size 100 patients). Participants, investigators, site staff, and study personnel involved in outcome assessment and data analysis were masked to group assignment. Patients with disease progression during masked treatment were unmasked; patients on placebo were offered open-label resminostat. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, defined as the time from randomisation to disease progression or death from any cause (whichever occurred first), analysed by intention to treat. This trial is registered with ClincalTrials.gov (NCT02953301) and has been completed.</p><p><strong>Findings: </strong>Between Jan 9, 2017, and May 11, 2022, 234 patients were screened for eligibility, of whom 201 (86%) patients were randomly assigned: 100 (50%) to resminostat and 101 (50%) to placebo. 123 (61%) participants were men and 78 (39%) were women, with a median age of 64 years (range 30-87). Most participants (173 [86%]) were White, 19 (9%) were Asian (mainly Japanese), two (1%) were Black, and seven (3%) were either another race or ethnicity, or did not disclose these data. Median progression-free survival was 8·3 months (95% CI 4·2-15·7) in the resminostat group and 4·2 months (2·8-6·4) in the placebo group (HR 0·62 [95% CI 0·42-0·92]; p=0·015). Median follow-up time for progression-free survival was 11·2 months (95% CI 5·6-19·6) in the resminostat group and 17·0 months (13·9-30·5) in the placebo group. Adverse events were reported in 96 (96%) patients receiving resminostat and in 81 (80%) patients receiving placebo. S
背景：在晚期皮肤t细胞淋巴瘤（CTCL）中，目前的治疗方案很少能提供持久的疗效。我们的目的是评估组蛋白去乙酰化酶抑制剂resminostat作为晚期蕈样真菌病或ssamzary综合征患者维持治疗的有效性和安全性，这些患者先前已经达到疾病控制。方法：我们在奥地利、比利时、法国、德国、希腊、意大利、荷兰、波兰、西班牙、瑞士、英国和日本的55个医疗中心进行了一项多中心、双盲、随机、安慰剂对照的2期试验（RESMAIN）。组织学证实的IIB-IVB期蕈样真菌病或ssamzary综合征的成年患者（年龄≥18岁）；a东部肿瘤合作组绩效状态评分0-2分；在至少一次以前的全身治疗或全皮肤电子束治疗后的疾病控制符合纳入条件。患者被随机分配接受口服雷米诺他（600毫克）或相匹配的口服安慰剂，每天一次，持续5天，随后在14天的治疗周期内无治疗9天。随机化根据疾病分期（IIB-IVA1 vs IVA2-IVB）和既往治疗后的缓解状态（完全或部分缓解vs疾病稳定）进行分层，采用动态分组分配过程（分组大小为100例）。参与结果评估和数据分析的参与者、研究者、现场工作人员和研究人员被分组分配。在蒙面治疗期间疾病进展的患者被揭开蒙面；服用安慰剂的患者给予开放标签的雷米司他。治疗持续到疾病进展或不可接受的毒性。主要终点是无进展生存期，定义为从随机化到疾病进展或任何原因死亡（以先发生者为准）的时间，并通过治疗意向进行分析。该试验已在clinaltrials .gov注册（NCT02953301），并已完成。研究结果：在2017年1月9日至2022年5月11日期间，筛选了234名患者，其中201名（86%）患者被随机分配：100名（50%）患者接受雷米诺他治疗，101名（50%）患者接受安慰剂治疗。123名（61%）参与者为男性，78名（39%）参与者为女性，中位年龄为64岁（30-87岁）。大多数参与者（173人[86%]）是白人，19人（9%）是亚洲人（主要是日本人），2人（1%）是黑人，7人（3%）是其他种族或族裔，或没有透露这些数据。雷米诺他组的中位无进展生存期为8.3个月（95% CI 4.2 - 15.7），安慰剂组的中位无进展生存期为4.2个月（2.8 - 6.4）（HR 0.62 [95% CI 0.42 - 0.92]; p= 0.015）。雷米诺他组无进展生存期的中位随访时间为11.2个月（95% CI为5.6 - 19.6），安慰剂组为17.0个月（13.9 - 30.5）。96例（96%）接受雷米司他治疗的患者报告了不良事件，81例（80%）接受安慰剂治疗的患者报告了不良事件。雷米司他组有19例（19%）患者发生严重不良事件，其中11例（11%）被认为与治疗有关，安慰剂组有12例（12%）患者发生严重不良事件，其中1例（1%）被认为与治疗有关。雷米诺他组38例（38%）患者发生3级或以上不良事件，安慰剂组15例（15%）患者发生3级或以上不良事件。最常见的治疗相关不良事件是恶心（雷米诺他组68例[68%]对安慰剂组6例[6%]）、腹泻（44例[44%]对9例[9%]）、呕吐（32例[32%]对1例[1%]）和疲劳（29例[29%]对14例[14%]）。没有与治疗相关的死亡。解释：这些发现支持雷米司他维持治疗对晚期CTCL患者的有益效果。瑞米司他的总体安全性是可以接受的，胃肠道副作用是最常见的。未来应考虑预防止吐，以控制副作用，提高耐受性和对维持治疗的依从性。资助：4SC AG。
{"title":"Resminostat for maintenance treatment in patients with advanced-stage mycosis fungoides or Sézary syndrome: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.","authors":"Rudolf Stadler, Pietro Quaglino, F J Sherida H Woei-A-Jin, Reinhard Dummer, Christina Mitteldorf, Evangelia Papadavid, Pablo L Ortiz Romero, Emmanuella Guenova, Riichiro Abe, Richard Cowan, Martine Bagot, Stéphane Dalle, Taku Fujimura, Thilo Gambichler, Stephen Morris, Ulrike Wehkamp, Patrick Terheyden, Antonio Cozzio, Edgar Dippel, Silvia Alberti-Violetti, Joanna Romejko-Jarosinska, Anna Wozniacka, Eva González Barca, Ramon Pujol Vallverdu, Egle Ramelyte, Oliver Bechter, Kenta Suzuki, Robert Knobler, Susanne Danhauser-Riedl, Julia Scarisbrick","doi":"10.1016/S2352-3026(25)00322-9","DOIUrl":"https://doi.org/10.1016/S2352-3026(25)00322-9","url":null,"abstract":"<p><strong>Background: </strong>In advanced-stage cutaneous T-cell lymphoma (CTCL), current therapeutic options rarely provide long-lasting responses. We aimed to evaluate the efficacy and safety of a histone deacetylase inhibitor, resminostat, as maintenance therapy in patients with advanced-stage mycosis fungoides or Sézary syndrome, in whom disease control had been previously met.</p><p><strong>Methods: </strong>We conducted a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial (RESMAIN) at 55 medical centres in Austria, Belgium, France, Germany, Greece, Italy, the Netherlands, Poland, Spain, Switzerland, the UK, and Japan. Adult patients (aged ≥18 years) with histologically confirmed, stage IIB-IVB mycosis fungoides or Sézary syndrome; an Eastern Cooperative Oncology Group performance status score of 0-2; and disease control after at least one previous systemic therapy or total skin electron beam were eligible for inclusion. Patients were randomly assigned to receive either oral resminostat (600 mg) or matching oral placebo once daily for 5 days, followed by a treatment-free period of 9 days, within a 14-day treatment cycle. Randomisation was stratified by disease stage (IIB-IVA1 vs IVA2-IVB) and remission status following previous therapy (complete or partial response vs stable disease) by use of a dynamic block allocation process (block size 100 patients). Participants, investigators, site staff, and study personnel involved in outcome assessment and data analysis were masked to group assignment. Patients with disease progression during masked treatment were unmasked; patients on placebo were offered open-label resminostat. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, defined as the time from randomisation to disease progression or death from any cause (whichever occurred first), analysed by intention to treat. This trial is registered with ClincalTrials.gov (NCT02953301) and has been completed.</p><p><strong>Findings: </strong>Between Jan 9, 2017, and May 11, 2022, 234 patients were screened for eligibility, of whom 201 (86%) patients were randomly assigned: 100 (50%) to resminostat and 101 (50%) to placebo. 123 (61%) participants were men and 78 (39%) were women, with a median age of 64 years (range 30-87). Most participants (173 [86%]) were White, 19 (9%) were Asian (mainly Japanese), two (1%) were Black, and seven (3%) were either another race or ethnicity, or did not disclose these data. Median progression-free survival was 8·3 months (95% CI 4·2-15·7) in the resminostat group and 4·2 months (2·8-6·4) in the placebo group (HR 0·62 [95% CI 0·42-0·92]; p=0·015). Median follow-up time for progression-free survival was 11·2 months (95% CI 5·6-19·6) in the resminostat group and 17·0 months (13·9-30·5) in the placebo group. Adverse events were reported in 96 (96%) patients receiving resminostat and in 81 (80%) patients receiving placebo. S","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"13 2","pages":"e98-e109"},"PeriodicalIF":17.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-01-16DOI: 10.1016/S2352-3026(25)00319-9
Stephen Kaptoge, Amy McMahon, Yaning Wu, Philippe T Gilchrist, Matthew Walker, Susan Mehenny, Naim Akhtar, Angela M Wood, Donna Cullen, Rosemary Godfrey, Louise Allen, John R Bradley, Nathalie Kingston, Charlotte Washington, Gail Miflin, Jane Armitage, David J Roberts, John Danesh, Emanuele Di Angelantonio
<p><strong>Background: </strong>Vasovagal reactions are the most common acute systemic complications of whole blood donations and are associated with significant morbidity and medicolegal costs. Blood services worldwide have implemented various strategies to prevent vasovagal reactions, often without robust evidence. We compared standard practice in England with four vasovagal reaction prevention interventions used in other services or previously tested in small-scale studies.</p><p><strong>Methods: </strong>This cluster-randomised, stepped-wedge, crossover trial involved 73 blood donation sites (clusters) across England, UK. Each site was randomly allocated to one of 64 possible sequences for implementing one or more of four interventions over four 9-month periods, yielding a total of 292 site-periods for a 36-month overall trial duration. Participants within each period were not unique, as repeat donations were included. Cluster randomisation was chosen for operational feasibility. Potential carry-over effects were minimised by use of stepped-wedge, crossover, and factorial design elements. The interventions assessed were: 500 mL pre-donation isotonic drink (vs standard 500 mL plain water), extended 3-minute post-donation rest on the donation chair (vs standard 2-minute rest), modified applied muscle tension (AMT) exercise (vs current AMT practice); and psychosocial intervention using preparatory materials (vs no materials). The primary outcome was in-session vasovagal reaction with loss of consciousness. Analysis was by intention-to-treat, including data from all donors attending the donation sites during the trial, unless the donor opted-out. This trial registered with isrctn.com (ISRCTN 10412338) and is complete.</p><p><strong>Findings: </strong>Between Nov 4, 2019, and Nov 3, 2022, we recruited 1 379 095 blood donors who made 4 134 712 blood donations. The median age of donors at time of baseline trial visit was 41 years (IQR 30-54), 785 271 (56·9%) of 1 379 095 donors were female and 593 824 (43·1%) were male. 461 954 (33·5%) were first-time donors. We recorded 4388 vasovagal reactions with loss of consciousness and 60 517 total in-session vasovagal reactions (ie, with and without loss of consciousness). Compared with standard practices, none of the interventions clearly reduced the primary outcome (joint p=0·21) with an odds ratio of 0·98 (95% CI 0·92-1·04) for isotonic drink, 0·99 (0·92-1·06) for extended chair rest, 1·12 (1·00-1·26) for modified AMT, and 1·03 (0·93-1·14) for psychosocial intervention. Absolute event rates per 10 000 donations were 10·7 without intervention and 10·5 with intervention. Findings were similar for total in-session vasovagal reactions with higher absolute event rates.</p><p><strong>Interpretation: </strong>Four interventions used to prevent donation-related vasovagal reactions showed no clear benefits compared with standard practices in England, suggesting potential policy implications for blood services worl
背景：血管迷走神经反应是全血捐献最常见的急性全身性并发症，与显著的发病率和医疗费用相关。世界各地的血液服务机构已经实施了各种预防血管迷走神经反应的策略，但往往缺乏有力的证据。我们比较了英国的标准做法和其他服务或小规模研究中使用的四种血管迷走神经反应预防干预措施。方法：该整群随机、楔形、交叉试验涉及英国、英格兰的73个献血点（群）。每个试验点被随机分配到64个可能序列中的一个，在4个9个月的时间内实施4种干预措施中的一种或多种，总共产生292个试验点，总试验时间为36个月。每个时期的参与者并不是唯一的，因为重复捐赠也包括在内。为了操作可行性，选择聚类随机化。通过使用楔形、交叉和析因设计元素，将潜在的携带效应降至最低。评估的干预措施为：捐赠前500毫升等渗饮料（相对于标准500毫升白开水），捐赠后在捐赠椅上延长3分钟休息时间（相对于标准2分钟休息时间），改良的应用肌肉张力（AMT）练习（相对于目前的AMT练习）；以及使用准备材料的心理社会干预（vs .不使用材料）。主要结局是治疗期间血管迷走神经反应伴意识丧失。通过意向治疗进行分析，包括在试验期间参加捐赠地点的所有献血者的数据，除非献血者选择退出。该试验已在isrctn.com注册（ISRCTN 10412338）并完成。在2019年11月4日至2022年11月3日期间，我们招募了1 379 095名献血者，他们进行了4 134 712次献血。基线试访时献血者年龄中位数为41岁（IQR 30-54岁），1 379 095名献血者中女性785 271人（56.9%），男性593 824人（43.1%）。首次献血者461 954人（33.5%）。我们记录了4388例失去意识的血管迷走神经反应和60517例完全在治疗过程中的血管迷走神经反应（即失去意识和不失去意识）。与标准做法相比，没有一项干预措施明显降低了主要结局（联合p= 0.21），等渗饮料的优势比为0.98 (95% CI 0.92 - 1.04)，延长椅子休息的优势比为0.99 (95% CI 0.92 - 1.06)，改良AMT的优势比为1.12 (95% CI 1.00 - 1.26)，心理社会干预的优势比为1.03 （95% CI 0.93 - 1.14）。无干预的绝对事件发生率为10.7 / 10000，干预的绝对事件发生率为10.5 / 10000。总的血管迷走神经反应的结果相似，但绝对事件发生率更高。解释：与英格兰的标准做法相比，用于预防献血相关血管迷走神经反应的四种干预措施没有明显的好处，这表明全球血液服务部门在简化献血实践和节约资源方面可能具有政策意义。资助：国家卫生服务体系血液和移植以及国家卫生研究院供体健康和行为血液和移植研究单位（原供体健康和基因组学）。
{"title":"Preventive interventions for vasovagal reactions in whole blood donors: a cluster-randomised, stepped-wedge, crossover trial of 73 sites involving 1·4 million donors in England.","authors":"Stephen Kaptoge, Amy McMahon, Yaning Wu, Philippe T Gilchrist, Matthew Walker, Susan Mehenny, Naim Akhtar, Angela M Wood, Donna Cullen, Rosemary Godfrey, Louise Allen, John R Bradley, Nathalie Kingston, Charlotte Washington, Gail Miflin, Jane Armitage, David J Roberts, John Danesh, Emanuele Di Angelantonio","doi":"10.1016/S2352-3026(25)00319-9","DOIUrl":"10.1016/S2352-3026(25)00319-9","url":null,"abstract":"<p><strong>Background: </strong>Vasovagal reactions are the most common acute systemic complications of whole blood donations and are associated with significant morbidity and medicolegal costs. Blood services worldwide have implemented various strategies to prevent vasovagal reactions, often without robust evidence. We compared standard practice in England with four vasovagal reaction prevention interventions used in other services or previously tested in small-scale studies.</p><p><strong>Methods: </strong>This cluster-randomised, stepped-wedge, crossover trial involved 73 blood donation sites (clusters) across England, UK. Each site was randomly allocated to one of 64 possible sequences for implementing one or more of four interventions over four 9-month periods, yielding a total of 292 site-periods for a 36-month overall trial duration. Participants within each period were not unique, as repeat donations were included. Cluster randomisation was chosen for operational feasibility. Potential carry-over effects were minimised by use of stepped-wedge, crossover, and factorial design elements. The interventions assessed were: 500 mL pre-donation isotonic drink (vs standard 500 mL plain water), extended 3-minute post-donation rest on the donation chair (vs standard 2-minute rest), modified applied muscle tension (AMT) exercise (vs current AMT practice); and psychosocial intervention using preparatory materials (vs no materials). The primary outcome was in-session vasovagal reaction with loss of consciousness. Analysis was by intention-to-treat, including data from all donors attending the donation sites during the trial, unless the donor opted-out. This trial registered with isrctn.com (ISRCTN 10412338) and is complete.</p><p><strong>Findings: </strong>Between Nov 4, 2019, and Nov 3, 2022, we recruited 1 379 095 blood donors who made 4 134 712 blood donations. The median age of donors at time of baseline trial visit was 41 years (IQR 30-54), 785 271 (56·9%) of 1 379 095 donors were female and 593 824 (43·1%) were male. 461 954 (33·5%) were first-time donors. We recorded 4388 vasovagal reactions with loss of consciousness and 60 517 total in-session vasovagal reactions (ie, with and without loss of consciousness). Compared with standard practices, none of the interventions clearly reduced the primary outcome (joint p=0·21) with an odds ratio of 0·98 (95% CI 0·92-1·04) for isotonic drink, 0·99 (0·92-1·06) for extended chair rest, 1·12 (1·00-1·26) for modified AMT, and 1·03 (0·93-1·14) for psychosocial intervention. Absolute event rates per 10 000 donations were 10·7 without intervention and 10·5 with intervention. Findings were similar for total in-session vasovagal reactions with higher absolute event rates.</p><p><strong>Interpretation: </strong>Four interventions used to prevent donation-related vasovagal reactions showed no clear benefits compared with standard practices in England, suggesting potential policy implications for blood services worl","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e64-e73"},"PeriodicalIF":17.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/S2352-3026(26)00003-7
Emma Wilkinson
{"title":"Jorge Cortes: building a network of leukaemia expertise in Latin America.","authors":"Emma Wilkinson","doi":"10.1016/S2352-3026(26)00003-7","DOIUrl":"https://doi.org/10.1016/S2352-3026(26)00003-7","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"13 2","pages":"e61"},"PeriodicalIF":17.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/S2352-3026(26)00001-3
Gerard Gurumurthy, Laura Knox, Jecko Thachil, Imelda Bates, Stephen P Hibbs
{"title":"Questions from the woman in the painting: revisiting chlorosis.","authors":"Gerard Gurumurthy, Laura Knox, Jecko Thachil, Imelda Bates, Stephen P Hibbs","doi":"10.1016/S2352-3026(26)00001-3","DOIUrl":"https://doi.org/10.1016/S2352-3026(26)00001-3","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"13 2","pages":"e62-e63"},"PeriodicalIF":17.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-02-02DOI: 10.1016/S2352-3026(25)00321-7
Prasanna Ananth, Jerlym S Porter, Jacklyn Boggs, Griffin Collins, Francesca A Williamson, Nitya Bakshi, Jane S Hankins, Liza-Marie Johnson, Ronit Elk, Dylan E Graetz, Erica C Kaye
Haematological disorders constitute a public health crisis in more than 160 countries worldwide. Despite millions afflicted, people with haematological diagnoses remain underserved and understudied. This Review, one of four companion Reviews on qualitative research published in The Lancet Oncology, The Lancet Haematology, and eClinicalMedicine, reports findings from a symposium of international multidisciplinary experts in applied qualitative research, highlighting the purpose and added value of qualitative research for improving health outcomes for people with haematological disorders and their communities. First, we describe how applied qualitative research elevates the voices of marginalised populations, review gaps in the current science, and present examples of impactful qualitative research in haematology across the research lifecycle. Second, we spotlight the need for global uptake of applied qualitative methods for people with haematological disorders to address questions related to health equity, care access, treatment adherence, and ethical implications of participation in therapeutic trials. Finally, we present an expert-informed roadmap for the conduct and appraisal of qualitative research in haematology comprising five pillars (engagement, flexibility, transparency, transferability, and impact) to promote best practices for applied qualitative research in haematology.
{"title":"Expert recommendations for the conduct and appraisal of qualitative research in haematology.","authors":"Prasanna Ananth, Jerlym S Porter, Jacklyn Boggs, Griffin Collins, Francesca A Williamson, Nitya Bakshi, Jane S Hankins, Liza-Marie Johnson, Ronit Elk, Dylan E Graetz, Erica C Kaye","doi":"10.1016/S2352-3026(25)00321-7","DOIUrl":"10.1016/S2352-3026(25)00321-7","url":null,"abstract":"<p><p>Haematological disorders constitute a public health crisis in more than 160 countries worldwide. Despite millions afflicted, people with haematological diagnoses remain underserved and understudied. This Review, one of four companion Reviews on qualitative research published in The Lancet Oncology, The Lancet Haematology, and eClinicalMedicine, reports findings from a symposium of international multidisciplinary experts in applied qualitative research, highlighting the purpose and added value of qualitative research for improving health outcomes for people with haematological disorders and their communities. First, we describe how applied qualitative research elevates the voices of marginalised populations, review gaps in the current science, and present examples of impactful qualitative research in haematology across the research lifecycle. Second, we spotlight the need for global uptake of applied qualitative methods for people with haematological disorders to address questions related to health equity, care access, treatment adherence, and ethical implications of participation in therapeutic trials. Finally, we present an expert-informed roadmap for the conduct and appraisal of qualitative research in haematology comprising five pillars (engagement, flexibility, transparency, transferability, and impact) to promote best practices for applied qualitative research in haematology.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e110-e118"},"PeriodicalIF":17.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1016/S2352-3026(25)00359-X
Fernando Barroso Duarte, Carmelo Gurnari, Donal P McLornan
The distinction between myelodysplastic syndromes and acute myeloid leukaemia remains a subject of debate, with direct implications for clinical decisions, trial eligibility, and allogeneic hematopoietic cell transplantation allocation. Although the historical 20% blast threshold in bone marrow is commonly used to separate myelodysplastic syndromes from acute myeloid leukaemia, emerging evidence shows that morphological, cytogenetic, and molecular features provide a more accurate framework for diagnosis and risk stratification. This Viewpoint discusses how advances in genomics and molecular biology have reshaped the classification of these disorders, highlighting molecular signatures and germline alterations as key tools to guide therapeutic decisions, transplant eligibility, and measurable residual disease assessment. We emphasise that myelodysplastic syndromes represent a biologically distinct entity to acute myeloid leukaemia, reinforcing the need to tailor treatment strategies according to disease biology to optimise patient outcomes.
{"title":"Myelodysplastic syndromes versus acute myeloid leukaemia: biology or blasts-what truly defines the disease and does it matter?","authors":"Fernando Barroso Duarte, Carmelo Gurnari, Donal P McLornan","doi":"10.1016/S2352-3026(25)00359-X","DOIUrl":"https://doi.org/10.1016/S2352-3026(25)00359-X","url":null,"abstract":"<p><p>The distinction between myelodysplastic syndromes and acute myeloid leukaemia remains a subject of debate, with direct implications for clinical decisions, trial eligibility, and allogeneic hematopoietic cell transplantation allocation. Although the historical 20% blast threshold in bone marrow is commonly used to separate myelodysplastic syndromes from acute myeloid leukaemia, emerging evidence shows that morphological, cytogenetic, and molecular features provide a more accurate framework for diagnosis and risk stratification. This Viewpoint discusses how advances in genomics and molecular biology have reshaped the classification of these disorders, highlighting molecular signatures and germline alterations as key tools to guide therapeutic decisions, transplant eligibility, and measurable residual disease assessment. We emphasise that myelodysplastic syndromes represent a biologically distinct entity to acute myeloid leukaemia, reinforcing the need to tailor treatment strategies according to disease biology to optimise patient outcomes.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":17.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/S2352-3026(25)00315-1
Tayyiba Wasim, Natasha Bushra, Tahira Nasrin, Shamsa Humayun, Arif Tajammul, Khadija Irfan Khawaja, Sonia Irshad, Sara Fatima, Adeela Yasin, Javier Zamora, Naomi Cano-Ibáñez, Borja Manuel Fernandez-Felix, Khalid Saeed Khan
<p><strong>Background: </strong>In non-anaemic iron deficiency during pregnancy, it remains unclear whether the administration of intravenous iron improves maternal and infant outcomes, compared with prophylactic oral iron that is currently recommended for antenatal care. This study evaluated whether the addition of intravenous iron to routine oral prophylaxis had an effect on maternal haemoglobin concentration before delivery in non-anaemic iron deficient pregnant women.</p><p><strong>Methods: </strong>In this multicentre, two-arm, randomised trial done at three teaching hospitals in Lahore, Pakistan, pregnant women aged 18 years or older with a singleton pregnancy were screened at the first antenatal care booking visit for non-anaemic iron deficiency (haemoglobin 11-13 g/dL at booking with ferritin <30 μg/L). Women with high haemoglobin concentrations were excluded. Participants were randomly assigned (1:1) to an intervention during the second trimester using serially numbered, opaque, identical boxes, prepared by a third party using computer-generated random numbers with variable block sizes. Participants were assigned to either receive 1000 mg of intravenous iron in addition to routine oral iron prophylaxis, or to receive prophylactic 30 mg oral iron daily as the standard of routine care throughout pregnancy. Outcome assessors were masked to group allocation. Participants were followed up to delivery. The primary outcome was the mean change in maternal haemoglobin concentration from baseline to 36 weeks' gestation. We performed the primary analysis applying the intention-to-treat principle in all randomly assigned participants who had data for the primary outcome available (full analysis set). We assessed participants for serious or life-threatening adverse events such as death, cardiac arrest, myocardial infarction, anaphylactic shock, and reactions leading to intensive care admission and discontinuation of treatment. The trial is registered at ClinicalTrials.gov number, NCT04228627, and is completed.</p><p><strong>Findings: </strong>Between Jan 14, 2020, to Aug 29, 2023, 1206 women were screened for eligibility, 606 were ineligible for participation due to reasons including age, gestational age, and haemoglobin concentration, and 600 were enrolled in the study. 295 women were assigned to the intravenous iron group and 305 were assigned to the oral iron prophylaxis group, and all were followed up until delivery. 228 women delivered in the intravenous iron group (14 preterm), and 234 women delivered in the oral iron prophylaxis group (21 preterm; three without primary outcome data). Maternal haemoglobin concentration before delivery was 11·6 g/dL (SD 0·5) in the intravenous iron group and 10·8 g/dL (0·7) in the prophylactic oral iron group (mean difference, 0·74 g/dL [95% CI 0·64-0·85]; p<0·0001). None of the participants experienced serious or life-threatening adverse events.</p><p><strong>Interpretation: </strong>Among non-anaemic iron defi
{"title":"Intravenous iron for non-anaemic iron deficiency in pregnancy: a multicentre, two-arm, randomised controlled trial.","authors":"Tayyiba Wasim, Natasha Bushra, Tahira Nasrin, Shamsa Humayun, Arif Tajammul, Khadija Irfan Khawaja, Sonia Irshad, Sara Fatima, Adeela Yasin, Javier Zamora, Naomi Cano-Ibáñez, Borja Manuel Fernandez-Felix, Khalid Saeed Khan","doi":"10.1016/S2352-3026(25)00315-1","DOIUrl":"10.1016/S2352-3026(25)00315-1","url":null,"abstract":"<p><strong>Background: </strong>In non-anaemic iron deficiency during pregnancy, it remains unclear whether the administration of intravenous iron improves maternal and infant outcomes, compared with prophylactic oral iron that is currently recommended for antenatal care. This study evaluated whether the addition of intravenous iron to routine oral prophylaxis had an effect on maternal haemoglobin concentration before delivery in non-anaemic iron deficient pregnant women.</p><p><strong>Methods: </strong>In this multicentre, two-arm, randomised trial done at three teaching hospitals in Lahore, Pakistan, pregnant women aged 18 years or older with a singleton pregnancy were screened at the first antenatal care booking visit for non-anaemic iron deficiency (haemoglobin 11-13 g/dL at booking with ferritin <30 μg/L). Women with high haemoglobin concentrations were excluded. Participants were randomly assigned (1:1) to an intervention during the second trimester using serially numbered, opaque, identical boxes, prepared by a third party using computer-generated random numbers with variable block sizes. Participants were assigned to either receive 1000 mg of intravenous iron in addition to routine oral iron prophylaxis, or to receive prophylactic 30 mg oral iron daily as the standard of routine care throughout pregnancy. Outcome assessors were masked to group allocation. Participants were followed up to delivery. The primary outcome was the mean change in maternal haemoglobin concentration from baseline to 36 weeks' gestation. We performed the primary analysis applying the intention-to-treat principle in all randomly assigned participants who had data for the primary outcome available (full analysis set). We assessed participants for serious or life-threatening adverse events such as death, cardiac arrest, myocardial infarction, anaphylactic shock, and reactions leading to intensive care admission and discontinuation of treatment. The trial is registered at ClinicalTrials.gov number, NCT04228627, and is completed.</p><p><strong>Findings: </strong>Between Jan 14, 2020, to Aug 29, 2023, 1206 women were screened for eligibility, 606 were ineligible for participation due to reasons including age, gestational age, and haemoglobin concentration, and 600 were enrolled in the study. 295 women were assigned to the intravenous iron group and 305 were assigned to the oral iron prophylaxis group, and all were followed up until delivery. 228 women delivered in the intravenous iron group (14 preterm), and 234 women delivered in the oral iron prophylaxis group (21 preterm; three without primary outcome data). Maternal haemoglobin concentration before delivery was 11·6 g/dL (SD 0·5) in the intravenous iron group and 10·8 g/dL (0·7) in the prophylactic oral iron group (mean difference, 0·74 g/dL [95% CI 0·64-0·85]; p<0·0001). None of the participants experienced serious or life-threatening adverse events.</p><p><strong>Interpretation: </strong>Among non-anaemic iron defi","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"13 1","pages":"e22-e29"},"PeriodicalIF":17.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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