Pub Date : 2024-12-01DOI: 10.1016/S2352-3026(24)00348-X
Maria Elisa Mancuso
{"title":"Non-replacement therapy for people with haemophilia B: another step towards health equity.","authors":"Maria Elisa Mancuso","doi":"10.1016/S2352-3026(24)00348-X","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00348-X","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 12","pages":"e880-e881"},"PeriodicalIF":15.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787457","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 : 2024-12-01Epub Date: 2024-11-08DOI: 10.1016/S2352-3026(24)00314-4
Derek P de Winter, Enrico Lopriore, Emilie Thorup, Olav Bjørn Petersen, Morten H Dziegiel, Karin Sundberg, Roland Devlieger, Luc de Catte, Liesbeth Lewi, Anne Debeer, Véronique Houfflin-Debarge, Louise Ghesquiere, Charles Garabedian, Kévin Le Duc, Eugenia Antolin, Nieves Mendez, James Castleman, Wing Ting Tse, Jean-Marie Jouannic, Paul Maurice, Jane Currie, Emma Mullen, Lut Geerts, Kerry Rademan, Asma Khalil, Borna Poljak, Smriti Prasad, Eleonor Tiblad, Kajsa Bohlin, Annegret Geipel, Johanna Rath, Fergal Malone, David Mackin, Yoav Yinon, Stav Cohen, Greg Ryan, Evangelia Vlachodimitropoulou, Karl-Philipp Gloning, Stefan Verlohren, Beate Mayer, Mariano Lanna, Stefano Faiola, Tanja Premru Sršen, Lilijana Kornhauser Cerar, Saul Snowise, Luming Sun, Lucas Otaño, César Hernan Meller, Ngina K Connors, Matthew Saxonhouse, Aline Wolter, Ivonne Bedei, Philipp Klaritsch, Sarah Jauch, Eduardo Teixeira da Silva Ribeiro, Fernando Maia Peixoto Filho, Raigam Jafet Martinez-Portilla, Alexandra Matias, Obdulia Alejos Abad, Juan Parra Roca, Ángel Guillermo Alcázar Grisi, Edgar Juan José Chávez Navarro, Johanna G van der Bom, Masja de Haas, Ejt Joanne Verweij
<p><strong>Background: </strong>Advances in haemolytic disease of the fetus and newborn have led to numerous treatment options. We report practice variations in the management and outcomes of haemolytic disease of the fetus and newborn in at-risk pregnancies.</p><p><strong>Methods: </strong>In this international, retrospective, observational cohort study, data from cases with moderate or severe haemolytic disease of the fetus and newborn were retrieved from 31 centres in 22 countries. Eligible participants had pregnancies with haemolytic disease of the fetus that led to fetal death at 16 + 0 weeks or later, those treated antenatally with intrauterine transfusion or intravenous immunoglobulins, or neonates without antenatal treatment who were treated with intensive phototherapy, exchange transfusion, or red blood cell transfusions. All patients had confirmed maternal alloantibodies and an antigen-positive fetus incompatible with the maternal alloantibody. Patients with ABO-incompatibility only were excluded. We assessed serological diagnostics and referrals, antenatal treatment and timing, complications, delivery route, and gestational age at birth. Outcomes were analysed in all eligible participants who had complete data available.</p><p><strong>Findings: </strong>2443 pregnancies with haemolytic disease of the fetus and newborn treated between Jan 1, 2006, and July 1, 2021, were shared by the centres and analysed between Dec 1, 2021, and March 1, 2023. 23 pregnancies were excluded due to missing information and we included 2420 for further analysis. 1764 (72·9%) of 2420 pregnancies were affected by D-antibodies. 95 (3·9%) of 2420 pregnancies resulted in fetal death. Of the 2325 liveborn neonates, 1349 (58·1%) received any form of antenatal treatment and 976 (41·9%) were only treated postnatally. Median gestational age at referral was 20·4 weeks (IQR 14·9-28·0) and ranged between medians of 10·0 and 26·3 weeks between centres. Severe hydrops at first intrauterine transfusion was present in 185 (14·5%) of 1276 pregnancies, with proportions ranging between 0 and 42% between centres. A median of two intrauterine transfusions (IQR 1-4) were done per pregnancy. The fetal access sites used in intrauterine transfusions varied widely between centres. Non-lethal complications in intrauterine transfusions by transfusion site occurred at a lower rate in intrahepatic approaches (2·0%, 95% CI 1·1-3·3) than in placental insertion (6·9%, 5·8-8·0) and free loop (13·3%, 8·9-18·9). The use and indication for intravenous immunoglobulin administration varied widely. Neonates with intrauterine transfusion were born at a median gestational age of 35·6 weeks (IQR 34·0-36·7), ranging between medians of 33·2 and 37·3 weeks between centres, while neonates without antenatal treatment were born at a median gestational age of 37·3 (IQR 36·3-38·1), ranging between medians of 34·9 and 38·9 weeks between centres.</p><p><strong>Interpretation: </strong>We found considerable vari
{"title":"Variations in antenatal management and outcomes in haemolytic disease of the fetus and newborn: an international, retrospective, observational cohort study.","authors":"Derek P de Winter, Enrico Lopriore, Emilie Thorup, Olav Bjørn Petersen, Morten H Dziegiel, Karin Sundberg, Roland Devlieger, Luc de Catte, Liesbeth Lewi, Anne Debeer, Véronique Houfflin-Debarge, Louise Ghesquiere, Charles Garabedian, Kévin Le Duc, Eugenia Antolin, Nieves Mendez, James Castleman, Wing Ting Tse, Jean-Marie Jouannic, Paul Maurice, Jane Currie, Emma Mullen, Lut Geerts, Kerry Rademan, Asma Khalil, Borna Poljak, Smriti Prasad, Eleonor Tiblad, Kajsa Bohlin, Annegret Geipel, Johanna Rath, Fergal Malone, David Mackin, Yoav Yinon, Stav Cohen, Greg Ryan, Evangelia Vlachodimitropoulou, Karl-Philipp Gloning, Stefan Verlohren, Beate Mayer, Mariano Lanna, Stefano Faiola, Tanja Premru Sršen, Lilijana Kornhauser Cerar, Saul Snowise, Luming Sun, Lucas Otaño, César Hernan Meller, Ngina K Connors, Matthew Saxonhouse, Aline Wolter, Ivonne Bedei, Philipp Klaritsch, Sarah Jauch, Eduardo Teixeira da Silva Ribeiro, Fernando Maia Peixoto Filho, Raigam Jafet Martinez-Portilla, Alexandra Matias, Obdulia Alejos Abad, Juan Parra Roca, Ángel Guillermo Alcázar Grisi, Edgar Juan José Chávez Navarro, Johanna G van der Bom, Masja de Haas, Ejt Joanne Verweij","doi":"10.1016/S2352-3026(24)00314-4","DOIUrl":"10.1016/S2352-3026(24)00314-4","url":null,"abstract":"<p><strong>Background: </strong>Advances in haemolytic disease of the fetus and newborn have led to numerous treatment options. We report practice variations in the management and outcomes of haemolytic disease of the fetus and newborn in at-risk pregnancies.</p><p><strong>Methods: </strong>In this international, retrospective, observational cohort study, data from cases with moderate or severe haemolytic disease of the fetus and newborn were retrieved from 31 centres in 22 countries. Eligible participants had pregnancies with haemolytic disease of the fetus that led to fetal death at 16 + 0 weeks or later, those treated antenatally with intrauterine transfusion or intravenous immunoglobulins, or neonates without antenatal treatment who were treated with intensive phototherapy, exchange transfusion, or red blood cell transfusions. All patients had confirmed maternal alloantibodies and an antigen-positive fetus incompatible with the maternal alloantibody. Patients with ABO-incompatibility only were excluded. We assessed serological diagnostics and referrals, antenatal treatment and timing, complications, delivery route, and gestational age at birth. Outcomes were analysed in all eligible participants who had complete data available.</p><p><strong>Findings: </strong>2443 pregnancies with haemolytic disease of the fetus and newborn treated between Jan 1, 2006, and July 1, 2021, were shared by the centres and analysed between Dec 1, 2021, and March 1, 2023. 23 pregnancies were excluded due to missing information and we included 2420 for further analysis. 1764 (72·9%) of 2420 pregnancies were affected by D-antibodies. 95 (3·9%) of 2420 pregnancies resulted in fetal death. Of the 2325 liveborn neonates, 1349 (58·1%) received any form of antenatal treatment and 976 (41·9%) were only treated postnatally. Median gestational age at referral was 20·4 weeks (IQR 14·9-28·0) and ranged between medians of 10·0 and 26·3 weeks between centres. Severe hydrops at first intrauterine transfusion was present in 185 (14·5%) of 1276 pregnancies, with proportions ranging between 0 and 42% between centres. A median of two intrauterine transfusions (IQR 1-4) were done per pregnancy. The fetal access sites used in intrauterine transfusions varied widely between centres. Non-lethal complications in intrauterine transfusions by transfusion site occurred at a lower rate in intrahepatic approaches (2·0%, 95% CI 1·1-3·3) than in placental insertion (6·9%, 5·8-8·0) and free loop (13·3%, 8·9-18·9). The use and indication for intravenous immunoglobulin administration varied widely. Neonates with intrauterine transfusion were born at a median gestational age of 35·6 weeks (IQR 34·0-36·7), ranging between medians of 33·2 and 37·3 weeks between centres, while neonates without antenatal treatment were born at a median gestational age of 37·3 (IQR 36·3-38·1), ranging between medians of 34·9 and 38·9 weeks between centres.</p><p><strong>Interpretation: </strong>We found considerable vari","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e927-e937"},"PeriodicalIF":15.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631184","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 : 2024-12-01DOI: 10.1016/S2352-3026(24)00285-0
Ibrahim Aldoss, Gail J Roboz, Renato Bassan, Nicolas Boissel, Daniel J DeAngelo, Shaun Fleming, Nicola Gökbuget, Aaron C Logan, Selina M Luger, Tobias Menne, Jae Park, Andre C Schuh, Bijal Shah, Elias Jabbour
In the past decade, there has been considerable progress in the treatment of adults with newly diagnosed B-cell acute lymphoblastic leukaemia. This evolution is the product of a more profound understanding of acute lymphoblastic leukaemia biology, innovations in measurable residual disease quantification that led to precise disease-risk stratification, adoption of contemporary paediatric-inspired regimens, inclusion of tyrosine kinase inhibitors in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia, and the introduction of immunotherapy in the frontline setting. Nevertheless, outcomes of acute lymphoblastic leukaemia in adults are inferior compared with those of children, with excessive rates of treatment failure, and therapy-related morbidity and mortality. Simultaneously, transplant consolidation has continued to be used frequently for high-risk adults with acute lymphoblastic leukaemia in first complete remission. Considering the rapid pace of evolution in acute lymphoblastic leukaemia management, novel trial designs are warranted to accelerate advancements and streamline approaches. Here, we summarise progress in the treatment of adults with newly diagnosed acute lymphoblastic leukaemia, which adds to previously published guidelines by focusing specifically on first-line decisions for B-cell acute lymphoblastic leukaemia and how to best personalise treatment. This Viewpoint also includes experiences with regimens and testing approaches currently available not only in Europe, but also on multiple continents with different practices and resources.
{"title":"Frontline treatment of adults with newly diagnosed B-cell acute lymphoblastic leukaemia.","authors":"Ibrahim Aldoss, Gail J Roboz, Renato Bassan, Nicolas Boissel, Daniel J DeAngelo, Shaun Fleming, Nicola Gökbuget, Aaron C Logan, Selina M Luger, Tobias Menne, Jae Park, Andre C Schuh, Bijal Shah, Elias Jabbour","doi":"10.1016/S2352-3026(24)00285-0","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00285-0","url":null,"abstract":"<p><p>In the past decade, there has been considerable progress in the treatment of adults with newly diagnosed B-cell acute lymphoblastic leukaemia. This evolution is the product of a more profound understanding of acute lymphoblastic leukaemia biology, innovations in measurable residual disease quantification that led to precise disease-risk stratification, adoption of contemporary paediatric-inspired regimens, inclusion of tyrosine kinase inhibitors in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia, and the introduction of immunotherapy in the frontline setting. Nevertheless, outcomes of acute lymphoblastic leukaemia in adults are inferior compared with those of children, with excessive rates of treatment failure, and therapy-related morbidity and mortality. Simultaneously, transplant consolidation has continued to be used frequently for high-risk adults with acute lymphoblastic leukaemia in first complete remission. Considering the rapid pace of evolution in acute lymphoblastic leukaemia management, novel trial designs are warranted to accelerate advancements and streamline approaches. Here, we summarise progress in the treatment of adults with newly diagnosed acute lymphoblastic leukaemia, which adds to previously published guidelines by focusing specifically on first-line decisions for B-cell acute lymphoblastic leukaemia and how to best personalise treatment. This Viewpoint also includes experiences with regimens and testing approaches currently available not only in Europe, but also on multiple continents with different practices and resources.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 12","pages":"e959-e970"},"PeriodicalIF":15.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787451","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 : 2024-12-01DOI: 10.1016/S2352-3026(24)00341-7
Bibi A Bassa, Briony Cutts, Fionnuala N Ainle
{"title":"Insights into antithrombotic therapy in pregnancy.","authors":"Bibi A Bassa, Briony Cutts, Fionnuala N Ainle","doi":"10.1016/S2352-3026(24)00341-7","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00341-7","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 12","pages":"e881-e882"},"PeriodicalIF":15.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787455","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 : 2024-12-01Epub Date: 2024-11-06DOI: 10.1016/S2352-3026(24)00307-7
Pratima Chowdary, Pantep Angchaisuksiri, Shashikant Apte, Jan Astermark, Gary Benson, Anthony K C Chan, Victor Jiménez Yuste, Tadashi Matsushita, Amalie Rhode Høgh Nielsen, Jameela Sathar, Christopher Sutton, Sonata Šaulytė Trakymienė, Huyen Tran, Laura Villarreal Martinez, Allison P Wheeler, Jerzy Windyga, Guy Young, Jay Jay Thaung Zaw, Hermann Eichler
<p><strong>Background: </strong>Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody in development as a once-daily, subcutaneous prophylaxis for patients with haemophilia A or haemophilia B with or without inhibitors. We aimed to assess the efficacy and safety of concizumab in patients with haemophilia A or B without inhibitors. Here we report the results from the confirmatory analysis cutoff.</p><p><strong>Methods: </strong>This prospective, multicentre, open-label, randomised, phase 3a trial (explorer8) was conducted at 69 investigational sites in 31 countries. Eligible patients were male, aged 12 years or older, and had congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors and with documented treatment with clotting factor concentrate in the 24 weeks before screening. The trial was paused because of non-fatal thromboembolic events in three patients (two from this trial [explorer8] and one from a related trial in haemophilia with inhibitors [explorer7; NCT04083781]) and restarted with mitigation measures, including a revised dosing regimen of subcutaneous concizumab at 1·0 mg/kg loading dose on day 1 and subsequent daily doses of 0·20 mg/kg from day 2, with options to decrease to 0·15 mg/kg, stay on 0·20 mg/kg, or increase to 0·25 mg/kg on the basis of concizumab plasma concentration measured after 4 weeks on concizumab. Patients recruited after treatment restart were randomly assigned 1:2 using an interactive web response system to receive no prophylaxis and continue on-demand clotting factor (group 1) or concizumab prophylaxis (group 2). The primary endpoints were the number of treated spontaneous and traumatic bleeding episodes for patients with haemophilia A and haemophilia B separately, assessed at the confirmatory analysis cutoff in randomly assigned patients. Analyses were by intention-to-treat. There were two additional groups containing non-randomly-assigned patients: group 3 contained patients who entered the trial before the trial pause and were receiving concizumab in the phase 2 trial (explorer5; NCT03196297), and group 4 contained patients who received previous clotting factor concentrate prophylaxis or on-demand treatment in the non-interventional trial (explorer6; NCT03741881), patients randomly assigned to groups 1 or 2 before the treatment pause, and patients from explorer5 enrolled after the treatment pause. The safety analysis set contained all patients who received concizumab. Superiority of concizumab over no prophylaxis was established if the two-sided 95% CI of the treatment ratio was less than 1 for haemophilia A and for haemophilia B. This trial is registered with ClinicalTrials.gov, NCT04082429, and its extension part is ongoing.</p><p><strong>Findings: </strong>Patients were recruited between Nov 13, 2019 and Nov 30, 2021; the cutoff date for the analyses presented was July 12, 2022. 173 patients were screened, of whom 148 (86%) were randomly assigned or allocate
背景介绍康妥珠单抗是一种抗组织因子通路抑制剂单克隆抗体，目前正在开发中，可作为血友病 A 或血友病 B 患者（无论有无抑制剂）的每日一次皮下注射预防用药。我们的目标是评估康妥珠单抗对无抑制剂的 A 型或 B 型血友病患者的疗效和安全性。在此，我们报告了确证分析截点的结果：这项前瞻性、多中心、开放标签、随机的 3a 期试验（Explorer8）在 31 个国家的 69 个研究机构进行。符合条件的患者均为男性，年龄在 12 岁或以上，患有先天性重度 A 型血友病或中度或重度 B 型血友病，无抑制剂，并在筛查前 24 周内接受过凝血因子浓缩治疗。由于三名患者（两名来自本试验[explorer8]，一名来自抑制剂血友病的相关试验[explorer7；NCT04083781]），并采取缓解措施重新开始治疗，包括修订给药方案：皮下注射康珠单抗，第1天的负荷剂量为1-0毫克/千克，从第2天开始，每天的剂量为0-20毫克/千克，可根据服用康珠单抗4周后测量的血浆浓度，选择降至0-15毫克/千克、维持0-20毫克/千克或增至0-25毫克/千克。治疗重新开始后招募的患者通过交互式网络响应系统以1:2的比例随机分配到不接受预防性治疗并继续按需使用凝血因子（第1组）或使用康珠单抗预防性治疗（第2组）。主要终点是在随机分配的患者中分别评估血友病 A 和血友病 B 患者经治疗的自发性和外伤性出血次数，以确认分析截止值为评估标准。分析采用意向治疗法。另外还有两组非随机分配的患者：第3组包括在试验暂停前加入试验并在2期试验中接受康妥珠单抗治疗的患者（explorer5；NCT03196297），第4组包括曾在非干预试验中接受凝血因子浓缩预防或按需治疗的患者（explorer6；NCT03741881）、在治疗暂停前随机分配到第1组或第2组的患者以及在治疗暂停后加入的explorer5患者。安全性分析集包括所有接受了康利珠单抗治疗的患者。如果A型血友病和B型血友病的治疗比值的双侧95% CI小于1，则确定使用康妥珠单抗优于不使用预防性治疗。该试验已在ClinicalTrials.gov上注册，编号为NCT04082429，其扩展部分正在进行中：患者招募时间为 2019 年 11 月 13 日至 2021 年 11 月 30 日；分析截止日期为 2022 年 7 月 12 日。共筛选出 173 名患者，其中 148 人（86%）在 2020 年 9 月 30 日试验重启后被随机分配或分配到研究的四个组别（第 1 组 9 名 A 型血友病患者和 12 名 B 型血友病患者；第 2 组 18 名 A 型血友病患者和 24 名 B 型血友病患者；第 3 组 9 名 A 型血友病患者；第 4 组 46 名 A 型血友病患者和 30 名 B 型血友病患者）。在使用康舒单抗预防治疗与不使用预防治疗期间，经治疗的自发性和外伤性出血发作的估计平均年化出血率比值为 0-14 (95% CI 0-07-0-29; p解释)：与不采取预防措施相比，康利珠单抗能有效降低出血率，而且对未服用抑制剂的 A 型或 B 型血友病患者是安全的。这项试验的结果表明，康利珠单抗有可能成为无抑制剂血友病 B 患者的首批皮下治疗选择之一：诺和诺德公司。
{"title":"Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial.","authors":"Pratima Chowdary, Pantep Angchaisuksiri, Shashikant Apte, Jan Astermark, Gary Benson, Anthony K C Chan, Victor Jiménez Yuste, Tadashi Matsushita, Amalie Rhode Høgh Nielsen, Jameela Sathar, Christopher Sutton, Sonata Šaulytė Trakymienė, Huyen Tran, Laura Villarreal Martinez, Allison P Wheeler, Jerzy Windyga, Guy Young, Jay Jay Thaung Zaw, Hermann Eichler","doi":"10.1016/S2352-3026(24)00307-7","DOIUrl":"10.1016/S2352-3026(24)00307-7","url":null,"abstract":"<p><strong>Background: </strong>Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody in development as a once-daily, subcutaneous prophylaxis for patients with haemophilia A or haemophilia B with or without inhibitors. We aimed to assess the efficacy and safety of concizumab in patients with haemophilia A or B without inhibitors. Here we report the results from the confirmatory analysis cutoff.</p><p><strong>Methods: </strong>This prospective, multicentre, open-label, randomised, phase 3a trial (explorer8) was conducted at 69 investigational sites in 31 countries. Eligible patients were male, aged 12 years or older, and had congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors and with documented treatment with clotting factor concentrate in the 24 weeks before screening. The trial was paused because of non-fatal thromboembolic events in three patients (two from this trial [explorer8] and one from a related trial in haemophilia with inhibitors [explorer7; NCT04083781]) and restarted with mitigation measures, including a revised dosing regimen of subcutaneous concizumab at 1·0 mg/kg loading dose on day 1 and subsequent daily doses of 0·20 mg/kg from day 2, with options to decrease to 0·15 mg/kg, stay on 0·20 mg/kg, or increase to 0·25 mg/kg on the basis of concizumab plasma concentration measured after 4 weeks on concizumab. Patients recruited after treatment restart were randomly assigned 1:2 using an interactive web response system to receive no prophylaxis and continue on-demand clotting factor (group 1) or concizumab prophylaxis (group 2). The primary endpoints were the number of treated spontaneous and traumatic bleeding episodes for patients with haemophilia A and haemophilia B separately, assessed at the confirmatory analysis cutoff in randomly assigned patients. Analyses were by intention-to-treat. There were two additional groups containing non-randomly-assigned patients: group 3 contained patients who entered the trial before the trial pause and were receiving concizumab in the phase 2 trial (explorer5; NCT03196297), and group 4 contained patients who received previous clotting factor concentrate prophylaxis or on-demand treatment in the non-interventional trial (explorer6; NCT03741881), patients randomly assigned to groups 1 or 2 before the treatment pause, and patients from explorer5 enrolled after the treatment pause. The safety analysis set contained all patients who received concizumab. Superiority of concizumab over no prophylaxis was established if the two-sided 95% CI of the treatment ratio was less than 1 for haemophilia A and for haemophilia B. This trial is registered with ClinicalTrials.gov, NCT04082429, and its extension part is ongoing.</p><p><strong>Findings: </strong>Patients were recruited between Nov 13, 2019 and Nov 30, 2021; the cutoff date for the analyses presented was July 12, 2022. 173 patients were screened, of whom 148 (86%) were randomly assigned or allocate","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e891-e904"},"PeriodicalIF":15.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631177","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 : 2024-12-01DOI: 10.1016/S2352-3026(24)00312-0
Neema P Mayor, Richard M Szydlo, Yasmin Sheikh, Julia Lee, Rachel M Pearce, Caitlin Farrow, Michaela Agapiou, Kanchan Rao, Kim Orchard, Eduardo Olavarria, Steven G E Marsh, John A Snowden
Background: Patient ethnicity has been correlated with different outcomes after haematopoietic cell transplantation (HCT), with patients from minority ethnic backgrounds reported to have worse outcomes compared with White patients. To date, studies have been predominantly done in the USA, where health-care models are different to many European countries, including the UK. We aimed to evaluate the impact of patient-reported ethnicity on autologous and allogeneic HCT outcomes in the UK.
Methods: In this retrospective cohort study, patients who had autologous or allogeneic HCT between Jan 1, 2009, and Dec 31, 2019, and were registered in the British Society of Blood and Marrow Transplantation and Cellular Therapy patient registry were analysed as full cohorts and as separate adult (≥18 years) and paediatric (0-17·9 years) cohorts. Patient ethnicity was self-defined and grouped into four broad categories: Asian, Black, Other, and White. The outcome was 5-year overall survival, with overall survival defined as the time from transplantation to death from any cause.
Findings: 20 119 first autologous HCTs and 13 978 first allogeneic HCTs were analysed. Median times to follow-up were 60 months (IQR 35-89) for patients receiving autologous HCT and 32 months (10-68) for patients receiving allogeneic HCT. 5-year overall survival for the full allogeneic HCT cohort was 55% (95% CI 51-58). After adjustment for prognostic factors, Asian patients undergoing allogeneic HCT (n=1081) had significantly worse 5-year overall survival (hazard ratio [HR] 1·16 [95% CI 1·03-1·30], p=0·012) than White patients (n=11 705). Differences in overall survival between White (n=1489) and Asian patients (n=384) were most pronounced in paediatric patients (HR 1·67 [95% CI 1·28-2·19], p=0·00018). In the autologous HCT cohort, there were no associations between ethnicity and 5-year overall survival.
Interpretation: This large UK-based analysis suggests significant variation in outcomes after allogeneic HCT between patients of different ethnicities. The causes are unclear, and further research to elucidate and improve these health inequalities is warranted.
Funding: Anthony Nolan Charity and British Society of Blood and Marrow Transplantation and Cellular Therapy.
背景：患者的种族与造血细胞移植（HCT）后的不同结果相关，据报道，少数民族背景的患者与白人患者相比预后更差。迄今为止，研究主要是在美国进行的，美国的医疗保健模式与包括英国在内的许多欧洲国家不同。我们的目的是评估英国患者报告的种族对自体和异体HCT结果的影响。方法：在这项回顾性队列研究中，2009年1月1日至2019年12月31日期间在英国血液和骨髓移植和细胞治疗协会患者登记处登记的自体或异体HCT患者被分为完整队列和单独的成人（≥18岁）和儿科（0- 17.9岁）队列进行分析。患者的种族是自我定义的，并分为四大类：亚洲人、黑人、其他人种和白人。结果是5年总生存率，总生存率定义为从移植到任何原因死亡的时间。结果：分析了20 119例首次自体hct和13 978例首次异体hct。接受自体HCT的患者中位随访时间为60个月（IQR 35-89），接受同种异体HCT的患者中位随访时间为32个月（10-68）。全同种异体HCT队列的5年总生存率为55% （95% CI 51-58）。校正预后因素后，接受同种异体HCT的亚洲患者（n=1081）的5年总生存率（风险比[HR] 1.16 [95% CI 1.03 -1·30],p= 0.012）明显低于白人患者（n=11 705）。白人（n=1489）和亚洲患者（n=384）的总生存率差异在儿科患者中最为明显（HR 1.67 [95% CI 1.28 -2·19],p= 0.00018）。在自体HCT队列中，种族与5年总生存率之间没有关联。解释：这项基于英国的大型分析表明，不同种族的患者接受同种异体HCT后的结果存在显著差异。原因尚不清楚，有必要进一步研究以阐明和改善这些健康不平等。资助：安东尼诺兰慈善机构和英国血液和骨髓移植和细胞治疗协会。
{"title":"The impact of patient ethnicity on haematopoietic cell transplantation outcome: a retrospective cohort study on the UK experience.","authors":"Neema P Mayor, Richard M Szydlo, Yasmin Sheikh, Julia Lee, Rachel M Pearce, Caitlin Farrow, Michaela Agapiou, Kanchan Rao, Kim Orchard, Eduardo Olavarria, Steven G E Marsh, John A Snowden","doi":"10.1016/S2352-3026(24)00312-0","DOIUrl":"10.1016/S2352-3026(24)00312-0","url":null,"abstract":"<p><strong>Background: </strong>Patient ethnicity has been correlated with different outcomes after haematopoietic cell transplantation (HCT), with patients from minority ethnic backgrounds reported to have worse outcomes compared with White patients. To date, studies have been predominantly done in the USA, where health-care models are different to many European countries, including the UK. We aimed to evaluate the impact of patient-reported ethnicity on autologous and allogeneic HCT outcomes in the UK.</p><p><strong>Methods: </strong>In this retrospective cohort study, patients who had autologous or allogeneic HCT between Jan 1, 2009, and Dec 31, 2019, and were registered in the British Society of Blood and Marrow Transplantation and Cellular Therapy patient registry were analysed as full cohorts and as separate adult (≥18 years) and paediatric (0-17·9 years) cohorts. Patient ethnicity was self-defined and grouped into four broad categories: Asian, Black, Other, and White. The outcome was 5-year overall survival, with overall survival defined as the time from transplantation to death from any cause.</p><p><strong>Findings: </strong>20 119 first autologous HCTs and 13 978 first allogeneic HCTs were analysed. Median times to follow-up were 60 months (IQR 35-89) for patients receiving autologous HCT and 32 months (10-68) for patients receiving allogeneic HCT. 5-year overall survival for the full allogeneic HCT cohort was 55% (95% CI 51-58). After adjustment for prognostic factors, Asian patients undergoing allogeneic HCT (n=1081) had significantly worse 5-year overall survival (hazard ratio [HR] 1·16 [95% CI 1·03-1·30], p=0·012) than White patients (n=11 705). Differences in overall survival between White (n=1489) and Asian patients (n=384) were most pronounced in paediatric patients (HR 1·67 [95% CI 1·28-2·19], p=0·00018). In the autologous HCT cohort, there were no associations between ethnicity and 5-year overall survival.</p><p><strong>Interpretation: </strong>This large UK-based analysis suggests significant variation in outcomes after allogeneic HCT between patients of different ethnicities. The causes are unclear, and further research to elucidate and improve these health inequalities is warranted.</p><p><strong>Funding: </strong>Anthony Nolan Charity and British Society of Blood and Marrow Transplantation and Cellular Therapy.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 12","pages":"e916-e926"},"PeriodicalIF":15.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787459","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 : 2024-12-01Epub Date: 2024-10-03DOI: 10.1016/S2352-3026(24)00311-9
Ariana Mihan
{"title":"The story of my zebra.","authors":"Ariana Mihan","doi":"10.1016/S2352-3026(24)00311-9","DOIUrl":"10.1016/S2352-3026(24)00311-9","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e889-e890"},"PeriodicalIF":15.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382089","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 : 2024-12-01DOI: 10.1016/S2352-3026(24)00313-2
Qingui Chen, Nienke van Rein, Lisa Broeders, Saskia Middeldorp, Kitty W M Bloemenkamp, Suzanne C Cannegieter, Luuk J J Scheres
Background: Considering the paucity of data, we aimed to describe nationwide time trends in antithrombotic therapy during pregnancy and risks of maternal and perinatal outcomes in the Netherlands.
Methods: In this nationwide cohort study, all female individuals aged 16-45 years with delivery records in the Dutch perinatal registry between Jan 1, 2013, and Dec 31, 2019, and their infants, were included. Individually linked data from Statistics Netherlands on outpatient medication prescriptions, in-hospital diagnoses, and mortality were used to evaluate time trends in antithrombotic therapy during pregnancy, and risks of maternal and perinatal outcomes (including thromboembolism, bleeding, preeclampsia and eclampsia, and low birthweight).
Findings: A total of 1 122 711 pregnancies and 1 139 116 infants were included (median maternal age 30·5 years [IQR 27·3-33·7]; 886 085 [78·9%] White; median gravidity 2 (IQR 1-3); and median gestational age at delivery 39 weeks [IQR 38-40]). Low-molecular-weight heparin (LMWH) was the most commonly (more than 99%) prescribed anticoagulants during pregnancy, which slightly increased from 0·7% (1063 of 163 479) in 2013 to 0·9% (1352 of 158 654) in 2019. LMWH was generally started at 5-8 weeks' gestation when oral anticoagulant prescriptions dropped. Antiplatelet drug prescriptions increased from 0·7% (1129 of 163 479) to 4·8% (7671 of 158 654), which primarily initiated around week 12. Maternal risks of venous and arterial thromboembolism and bleeding remained constant from 2013 to 2019; the risk of preeclampsia and eclampsia gradually increased from 1·70% (95% CI 1·63-1·76) in 2013 to 2·05% (1·98-2·13) in 2017, after which it decreased to 1·83% (1·77-1·90) in 2019. There was a significant decrease (2019 vs 2013) in low birthweight (adjusted odds ratio 0·92 [0·90-0·94]; p<0·0001), whereas 28-day neonatal bleeding risk remained unchanged.
Interpretation: Exposure to anticoagulants during pregnancy is not uncommon, and health-care providers and female individuals of reproductive age should be mindful of this to avoid unintended oral anticoagulant exposure. Adhering to guidelines for aspirin use to prevent preeclampsia might lead to a population-level reduction in disease burden and potential improvement in neonatal prognosis.
Funding: None.
Translation: For the Dutch translation of the abstract see Supplementary Materials section.
{"title":"Time trends in antithrombotic therapy during pregnancy and maternal and perinatal outcomes in the Netherlands (2013-19): a nationwide cohort study.","authors":"Qingui Chen, Nienke van Rein, Lisa Broeders, Saskia Middeldorp, Kitty W M Bloemenkamp, Suzanne C Cannegieter, Luuk J J Scheres","doi":"10.1016/S2352-3026(24)00313-2","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00313-2","url":null,"abstract":"<p><strong>Background: </strong>Considering the paucity of data, we aimed to describe nationwide time trends in antithrombotic therapy during pregnancy and risks of maternal and perinatal outcomes in the Netherlands.</p><p><strong>Methods: </strong>In this nationwide cohort study, all female individuals aged 16-45 years with delivery records in the Dutch perinatal registry between Jan 1, 2013, and Dec 31, 2019, and their infants, were included. Individually linked data from Statistics Netherlands on outpatient medication prescriptions, in-hospital diagnoses, and mortality were used to evaluate time trends in antithrombotic therapy during pregnancy, and risks of maternal and perinatal outcomes (including thromboembolism, bleeding, preeclampsia and eclampsia, and low birthweight).</p><p><strong>Findings: </strong>A total of 1 122 711 pregnancies and 1 139 116 infants were included (median maternal age 30·5 years [IQR 27·3-33·7]; 886 085 [78·9%] White; median gravidity 2 (IQR 1-3); and median gestational age at delivery 39 weeks [IQR 38-40]). Low-molecular-weight heparin (LMWH) was the most commonly (more than 99%) prescribed anticoagulants during pregnancy, which slightly increased from 0·7% (1063 of 163 479) in 2013 to 0·9% (1352 of 158 654) in 2019. LMWH was generally started at 5-8 weeks' gestation when oral anticoagulant prescriptions dropped. Antiplatelet drug prescriptions increased from 0·7% (1129 of 163 479) to 4·8% (7671 of 158 654), which primarily initiated around week 12. Maternal risks of venous and arterial thromboembolism and bleeding remained constant from 2013 to 2019; the risk of preeclampsia and eclampsia gradually increased from 1·70% (95% CI 1·63-1·76) in 2013 to 2·05% (1·98-2·13) in 2017, after which it decreased to 1·83% (1·77-1·90) in 2019. There was a significant decrease (2019 vs 2013) in low birthweight (adjusted odds ratio 0·92 [0·90-0·94]; p<0·0001), whereas 28-day neonatal bleeding risk remained unchanged.</p><p><strong>Interpretation: </strong>Exposure to anticoagulants during pregnancy is not uncommon, and health-care providers and female individuals of reproductive age should be mindful of this to avoid unintended oral anticoagulant exposure. Adhering to guidelines for aspirin use to prevent preeclampsia might lead to a population-level reduction in disease burden and potential improvement in neonatal prognosis.</p><p><strong>Funding: </strong>None.</p><p><strong>Translation: </strong>For the Dutch translation of the abstract see Supplementary Materials section.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 12","pages":"e905-e915"},"PeriodicalIF":15.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787463","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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