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Hydroxyurea dose optimisation for children with sickle cell anaemia in sub-Saharan Africa (REACH): extended follow-up of a multicentre, open-label, phase 1/2 trial. 撒哈拉以南非洲镰状细胞贫血患儿的羟基脲剂量优化(REACH):多中心、开放标签、1/2 期试验的扩展随访。
IF 15.4 1区 医学
Lancet Haematology Pub Date : 2024-06-01 Epub Date: 2024-04-30 DOI: 10.1016/S2352-3026(24)00078-4
Banu Aygun, Adam Lane, Luke R Smart, Brígida Santos, Léon Tshilolo, Thomas N Williams, Peter Olupot-Olupot, Susan E Stuber, George Tomlinson, Teresa Latham, Russell E Ware
{"title":"Hydroxyurea dose optimisation for children with sickle cell anaemia in sub-Saharan Africa (REACH): extended follow-up of a multicentre, open-label, phase 1/2 trial.","authors":"Banu Aygun, Adam Lane, Luke R Smart, Brígida Santos, Léon Tshilolo, Thomas N Williams, Peter Olupot-Olupot, Susan E Stuber, George Tomlinson, Teresa Latham, Russell E Ware","doi":"10.1016/S2352-3026(24)00078-4","DOIUrl":"10.1016/S2352-3026(24)00078-4","url":null,"abstract":"<p><strong>Background: </strong>Realizing Effectiveness Across Continents with Hydroxyurea (REACH) is an open-label non-randomised trial of hydroxyurea (hydroxycarbamide) in children with sickle cell anaemia in sub-Saharan Africa. The short-term results of REACH on safety, feasibility, and effectiveness of hydroxyurea were published previously. In this paper we report results from extended hydroxyurea treatment in the REACH cohort up to 8 years.</p><p><strong>Methods: </strong>In this open-label, non-randomised, phase 1/2 trial, participants were recruited from four clinical sites in Kilifi, Kenya; Mbale, Uganda; Luanda, Angola; and Kinshasa, Democratic Republic of Congo. Eligible children were 1-10 years old with documented haemoglobin SS or haemoglobin Sβ zero thalassaemia, weighing at least 10 kg. Participants received fixed-dose hydroxyurea of 17.5 (±2.5) mg/kg per day for 6 months (fixed-dose phase), followed by 6 months of dose escalation (2·5-5·0 mg/kg increments every 8 weeks) as tolerated, up to 20-35 mg/kg per day (maximum tolerated dose; MTD), defined as mild myelosuppression. After the MTD was reached, hydroxyurea dosing was optimised for each participant on the basis of changes in bodyweight and laboratory values over time (MTD with optimisation phase). After completion of the first 12 months, children with an acceptable toxicity profile and favourable responses were given the opportunity to continue hydroxyurea until the age of 18 years. The safety and feasibility results after 3 years has been reported previously. Here, haematological responses, clinical events, and toxicity rates were compared across the dosing phases (fixed-dose hydroxyurea vs MTD with optimisation phase) as protocol-specified outcomes. REACH is registered on ClinicalTrials.gov (NCT01966731) and is ongoing.</p><p><strong>Findings: </strong>We enrolled 635 children between July 4, 2014, and Nov 11, 2016. 606 children were given hydroxyurea and 522 (86%; 266 [51%] boys and 256 [49%] girls) received treatment for a median of 93 months (IQR 84-97) with 4340 patient-years of treatment. The current (Oct 5, 2023) mean dose is 28·2 (SD 5·2) mg/kg per day with an increased mean haemoglobin concentration (7·3 [SD 1·1] g/dL at baseline to 8·5 [1·5] g/dL) and mean fetal haemoglobin level (10·9% [SD 6·8] to 23·3% [9·5]) and decreased absolute neutrophil count (6·8 [3·0] × 10<sup>9</sup> cells per L to 3·6 [2·2] × 10<sup>9</sup> cells per L). Incidence rate ratios (IRR) comparing MTD with fixed-dose hydroxyurea indicate decreased vaso-occlusive episodes (0·60; 95% CI 0·52-0·70; p<0·0001), acute chest syndrome events (0·21; 0·13-0·33; p<0·0001), recurrent stroke events (0·27; 0·07-1·06; p=0·061), malaria infections (0·58; 0·46-0·72; p<0·0001), non-malarial infections (0·52; 0·46-0·58; p<0·0001), serious adverse events (0·42; 0·27-0·67; p<0·0001), and death (0·70; 0·25-1·97; p=0·50). Dose-limiting toxicity rates were similar between the fixed-dose (24·1 per 100 patient-years) an","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e425-e435"},"PeriodicalIF":15.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Striking the right balance. 取得适当的平衡。
IF 24.7 1区 医学
Lancet Haematology Pub Date : 2024-06-01 DOI: 10.1016/S2352-3026(24)00146-7
Alexander Coltoff
{"title":"Striking the right balance.","authors":"Alexander Coltoff","doi":"10.1016/S2352-3026(24)00146-7","DOIUrl":"10.1016/S2352-3026(24)00146-7","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 6","pages":"e402"},"PeriodicalIF":24.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155827","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}
引用次数: 0
Anti-CD30 CAR T cells as consolidation after autologous haematopoietic stem-cell transplantation in patients with high-risk CD30+ lymphoma: a phase 1 study. 抗 CD30 CAR T 细胞作为高危 CD30+ 淋巴瘤患者自体造血干细胞移植后的巩固治疗:1 期研究。
IF 15.4 1区 医学
Lancet Haematology Pub Date : 2024-05-01 Epub Date: 2024-03-28 DOI: 10.1016/S2352-3026(24)00064-4
Natalie S Grover, George Hucks, Marcie L Riches, Anastasia Ivanova, Dominic T Moore, Thomas C Shea, Mary Beth Seegars, Paul M Armistead, Kimberly A Kasow, Anne W Beaven, Christopher Dittus, James M Coghill, Katarzyna J Jamieson, Benjamin G Vincent, William A Wood, Catherine Cheng, Julia Kaitlin Morrison, John West, Tammy Cavallo, Gianpietro Dotti, Jonathan S Serody, Barbara Savoldo
{"title":"Anti-CD30 CAR T cells as consolidation after autologous haematopoietic stem-cell transplantation in patients with high-risk CD30<sup>+</sup> lymphoma: a phase 1 study.","authors":"Natalie S Grover, George Hucks, Marcie L Riches, Anastasia Ivanova, Dominic T Moore, Thomas C Shea, Mary Beth Seegars, Paul M Armistead, Kimberly A Kasow, Anne W Beaven, Christopher Dittus, James M Coghill, Katarzyna J Jamieson, Benjamin G Vincent, William A Wood, Catherine Cheng, Julia Kaitlin Morrison, John West, Tammy Cavallo, Gianpietro Dotti, Jonathan S Serody, Barbara Savoldo","doi":"10.1016/S2352-3026(24)00064-4","DOIUrl":"10.1016/S2352-3026(24)00064-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chimeric antigen receptor (CAR) T cells targeting CD30 are safe and have promising activity when preceded by lymphodepleting chemotherapy. We aimed to determine the safety of anti-CD30 CAR T cells as consolidation after autologous haematopoietic stem-cell transplantation (HSCT) in patients with CD30&lt;sup&gt;+&lt;/sup&gt; lymphoma at high risk of relapse.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This phase 1 dose-escalation study was performed at two sites in the USA. Patients aged 3 years and older, with classical Hodgkin lymphoma or non-Hodgkin lymphoma with CD30&lt;sup&gt;+&lt;/sup&gt; disease documented by immunohistochemistry, and a Karnofsky performance score of more than 60% planned for autologous HSCT were eligible if they were considered high risk for relapse as defined by primary refractory disease or relapse within 12 months of initial therapy or extranodal involvement at the start of pre-transplantation salvage therapy. Patients received a single infusion of CAR T cells (2 × 10&lt;sup&gt;7&lt;/sup&gt; CAR T cells per m&lt;sup&gt;2&lt;/sup&gt;, 1 × 10&lt;sup&gt;8&lt;/sup&gt; CAR T cells per m&lt;sup&gt;2&lt;/sup&gt;, or 2 × 10&lt;sup&gt;8&lt;/sup&gt; CAR T cells per m&lt;sup&gt;2&lt;/sup&gt;) as consolidation after trilineage haematopoietic engraftment (defined as absolute neutrophil count ≥500 cells per μL for 3 days, platelet count ≥25 × 10&lt;sup&gt;9&lt;/sup&gt; platelets per L without transfusion for 5 days, and haemoglobin ≥8 g/dL without transfusion for 5 days) following carmustine, etoposide, cytarabine, and melphalan (BEAM) and HSCT. The primary endpoint was the determination of the maximum tolerated dose, which was based on the rate of dose-limiting toxicity in patients who received CAR T-cell infusion. This study is registered with ClinicalTrials.gov (NCT02663297) and enrolment is complete.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between June 7, 2016, and Nov 30, 2020, 21 patients were enrolled and 18 patients (11 with Hodgkin lymphoma, six with T-cell lymphoma, one with grey zone lymphoma) were infused with anti-CD30 CAR T cells at a median of 22 days (range 16-44) after autologous HSCT. There were no dose-limiting toxicities observed, so the highest dose tested, 2 × 10&lt;sup&gt;8&lt;/sup&gt; CAR T cells per m&lt;sup&gt;2&lt;/sup&gt;, was determined to be the maximum tolerated dose. One patient had grade 1 cytokine release syndrome. The most common grade 3-4 adverse events were lymphopenia (two [11%] of 18) and leukopenia (two [11%] of 18). There were no treatment-related deaths. Two patients developed secondary malignancies approximately 2 years and 2·5 years following treatment (one stage 4 non-small cell lung cancer and one testicular cancer), but these were judged unrelated to treatment. At a median follow-up of 48·2 months (IQR 27·5-60·7) post-infusion, the median progression-free survival for all treated patients (n=18) was 32·3 months (95% CI 4·6 months to not estimable) and the median progression-free survival for treated patients with Hodgkin lymphoma (n=11) has not been reached. The median overall survival for all treated pat","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e358-e367"},"PeriodicalIF":15.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140332207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alexis Thompson: advancing care for sickle cell disease. 亚历克西斯-汤普森:推进镰状细胞病的治疗。
IF 24.7 1区 医学
Lancet Haematology Pub Date : 2024-05-01 DOI: 10.1016/S2352-3026(24)00108-X
Udani Samarasekera
{"title":"Alexis Thompson: advancing care for sickle cell disease.","authors":"Udani Samarasekera","doi":"10.1016/S2352-3026(24)00108-X","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00108-X","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 5","pages":"e321"},"PeriodicalIF":24.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855603","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}
引用次数: 0
First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): a multicentre, single-arm, phase 2 trial. 晚期结节外自然杀伤/T细胞淋巴瘤(SPIRIT)的一线辛替利单抗联合培加司琼、吉西他滨和奥沙利铂治疗:一项多中心、单臂、2期试验。
IF 24.7 1区 医学
Lancet Haematology Pub Date : 2024-05-01 Epub Date: 2024-03-27 DOI: 10.1016/S2352-3026(24)00066-8
Xiao-Peng Tian, Jun Cai, Yi Xia, Yu-Chen Zhang, Liang Wang, Pan-Pan Liu, Hui-Qiang Huang, Ya-Jun Li, Hui Zhou, Zhi-Ming Li, Jing Yang, Li-Qiang Wei, Qi-Hua Zou, Ying Huang, Jun Li, Li Ling, Wen-Long Zhong, Qing-Qing Cai
{"title":"First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): a multicentre, single-arm, phase 2 trial.","authors":"Xiao-Peng Tian, Jun Cai, Yi Xia, Yu-Chen Zhang, Liang Wang, Pan-Pan Liu, Hui-Qiang Huang, Ya-Jun Li, Hui Zhou, Zhi-Ming Li, Jing Yang, Li-Qiang Wei, Qi-Hua Zou, Ying Huang, Jun Li, Li Ling, Wen-Long Zhong, Qing-Qing Cai","doi":"10.1016/S2352-3026(24)00066-8","DOIUrl":"10.1016/S2352-3026(24)00066-8","url":null,"abstract":"<p><strong>Background: </strong>Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed and refractory extranodal natural killer/T cell lymphoma (ENKTL), nasal type. We aimed to assess the safety and activity of sintilimab plus P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) in the first-line setting for advanced ENKTL.</p><p><strong>Methods: </strong>The multicentre, single-arm, phase 2 trial was done at three medical centres in China. Patients aged 18-75 years with treatment-naive pathologically confirmed advanced ENKTL and an with Eastern Cooperative Oncology Group performance status score of 0-2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m<sup>2</sup> on day 1), intravenous gemcitabine (1 g/m<sup>2</sup> on days 1 and 8), and intravenous oxaliplatin (130 mg/m<sup>2</sup> on day 1) every 3 weeks for six cycles, followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint was the complete response rate in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival. This trial is registered with ClinicalTrials.gov, NCT04127227. Enrolment has been completed, and follow-up is ongoing.</p><p><strong>Findings: </strong>Between Nov 29, 2019, and Sept 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32-55]; 25 [74%] of 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cutoff (July 20, 2023), the median follow-up was 21 months (IQR 13-32). The complete response rate was 85% (29 of 34 patients, 95% CI 70-94). Five patients (15%; 95% CI 7-30) attained partial response and the ORR was 100% (34 of 34 patients). 24-month PFS was 64% (95% CI 48-86), 24-month DFS was 72% (54-95), and 36-month overall survival was 76% (52-100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one (3%) patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered to be treatment related.</p><p><strong>Interpretation: </strong>Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced ENKTL.</p><p><strong>Funding: </strong>National Key Research and Development Program and National Natural Science Foundation of China, Guangzhou Science and Technology Program and the Clinical Oncology Foundation of Chinese Society of Clinical Oncology.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e336-e344"},"PeriodicalIF":24.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330171","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}
引用次数: 0
Riociguat shows remarkable safety but underwhelming activity in patients with sickle cell disease. Riociguat 在镰状细胞病患者中显示出显著的安全性,但活性却不尽人意。
IF 15.4 1区 医学
Lancet Haematology Pub Date : 2024-05-01 Epub Date: 2024-03-27 DOI: 10.1016/S2352-3026(24)00079-6
Emily M Limerick, Courtney D Fitzhugh
{"title":"Riociguat shows remarkable safety but underwhelming activity in patients with sickle cell disease.","authors":"Emily M Limerick, Courtney D Fitzhugh","doi":"10.1016/S2352-3026(24)00079-6","DOIUrl":"10.1016/S2352-3026(24)00079-6","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e313-e314"},"PeriodicalIF":15.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330173","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}
引用次数: 0
Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1-2 trial. 治疗镰状细胞病患者高血压或蛋白尿的 Riociguat(STERIO-SCD):一项随机、双盲、安慰剂对照的 1-2 期试验。
IF 24.7 1区 医学
Lancet Haematology Pub Date : 2024-05-01 Epub Date: 2024-03-27 DOI: 10.1016/S2352-3026(24)00045-0
Mark T Gladwin, Victor R Gordeuk, Payal C Desai, Caterina Minniti, Enrico M Novelli, Claudia R Morris, Kenneth I Ataga, Laura De Castro, Susanna A Curtis, Fuad El Rassi, Hubert James Ford, Thomas Harrington, Elizabeth S Klings, Sophie Lanzkron, Darla Liles, Jane Little, Alecia Nero, Wally Smith, James G Taylor, Ayanna Baptiste, Ward Hagar, Julie Kanter, Amy Kinzie, Temeia Martin, Amina Rafique, Marilyn J Telen, Christina M Lalama, Gregory J Kato, Kaleab Z Abebe
{"title":"Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1-2 trial.","authors":"Mark T Gladwin, Victor R Gordeuk, Payal C Desai, Caterina Minniti, Enrico M Novelli, Claudia R Morris, Kenneth I Ataga, Laura De Castro, Susanna A Curtis, Fuad El Rassi, Hubert James Ford, Thomas Harrington, Elizabeth S Klings, Sophie Lanzkron, Darla Liles, Jane Little, Alecia Nero, Wally Smith, James G Taylor, Ayanna Baptiste, Ward Hagar, Julie Kanter, Amy Kinzie, Temeia Martin, Amina Rafique, Marilyn J Telen, Christina M Lalama, Gregory J Kato, Kaleab Z Abebe","doi":"10.1016/S2352-3026(24)00045-0","DOIUrl":"10.1016/S2352-3026(24)00045-0","url":null,"abstract":"<p><strong>Background: </strong>Although nitric oxide based therapeutics have been shown in preclinical models to reduce vaso-occlusive events and improve cardiovascular function, a clinical trial of a phosphodiesterase 5 inhibitor increased rates of admission to hospital for pain. We aimed to examine if riociguat, a direct stimulator of the nitric oxide receptor soluble guanylate cyclase, causes similar increases in vaso-occlusive events.</p><p><strong>Methods: </strong>This was a phase 1-2, randomised, double blind, placebo-controlled trial. Eligible patients were 18 years or older, had confirmed sickle cell disease documented by haemoglobin electrophoresis or HPLC fractionation (haemoglobin SS, SC, Sβ-thalassemia, SD, or SO-Arab), and stage 1 hypertension or proteinuria. Participants were randomly assigned 1:1 to receive either riociguat or matching placebo via a web-based system to maintain allocation concealment. Both treatments were administered orally starting at 1·0 mg three times a day up to 2·5 mg three times a day (highest tolerated dose) for 12 weeks. Dose escalation by 0·5 mg was considered every 2 weeks if systolic blood pressure was greater than 95 mm Hg and the participant had no signs of hypotension; otherwise, the last dose was maintained. The primary outcome was the proportion of participants who had at least one adjudicated treatment-emergent serious adverse event. The analysis was performed by the intention-to-treat. This trial is registered with ClinicalTrials.gov (NCT02633397) and was completed.</p><p><strong>Findings: </strong>Between April 11, 2017, and Dec 31, 2021, 165 participants were screened and consented to be enrolled into the study. Of these, 130 participants were randomly assigned to either riociguat (n=66) or placebo (n=64). The proportion of participants with at least one treatment-emergent serious adverse event was 22·7% (n=15) in the riociguat group and 31·3% (n=20) in the placebo group (difference -8·5% [90% CI -21·4 to 4·5]; p=0·19). A similar pattern emerged in other key safety outcomes, sickle cell related vaso-occlusive events (16·7 [n=11] vs 21·9% [n=14]; difference -5·2% [-17·2 to 6·5]; p=0·42), mean pain severity (3·18 vs 3·32; adjusted mean difference -0·14 [-0·70 to 0·42]; p=0·69), and pain interference (3·15 vs 3·12; 0·04 [-0·62 to 0·69]; p=0·93) at 12 weeks were similar between groups. Regarding the key clinical efficacy endpoints, participants taking riociguat had a blood pressure of -8·20 mm Hg (-10·48 to -5·91) compared with -1·24 (-3·58 to 1·10) in those taking placebo (-6·96 mm Hg (90% CI -10·22 to -3·69; p<0·001).</p><p><strong>Interpretation: </strong>Riociguat was safe and had a significant haemodynamic effect on systemic blood pressure. The results of this study provide measures of effect and variability that will inform power calculations for future trials.</p><p><strong>Funding: </strong>Bayer Pharmaceuticals.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e345-e357"},"PeriodicalIF":24.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330172","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}
引用次数: 0
Doggedly first-hand: a medical memoir that does not step outside itself. 坚持不懈的第一手资料:一本没有跳出自身局限的医学回忆录。
IF 24.7 1区 医学
Lancet Haematology Pub Date : 2024-05-01 DOI: 10.1016/S2352-3026(24)00107-8
Catherine Lucas
{"title":"Doggedly first-hand: a medical memoir that does not step outside itself.","authors":"Catherine Lucas","doi":"10.1016/S2352-3026(24)00107-8","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00107-8","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 5","pages":"e320"},"PeriodicalIF":24.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865844","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}
引用次数: 0
Diagnosis, treatment, and surveillance of Diamond-Blackfan anaemia syndrome: international consensus statement. 钻石-贝克范贫血综合征的诊断、治疗和监测:国际共识声明。
IF 15.4 1区 医学
Lancet Haematology Pub Date : 2024-05-01 DOI: 10.1016/S2352-3026(24)00063-2
Marcin W Wlodarski, Adrianna Vlachos, Jason E Farrar, Lydie M Da Costa, Antonis Kattamis, Irma Dianzani, Cristina Belendez, Sule Unal, Hannah Tamary, Ramune Pasauliene, Dagmar Pospisilova, Josu de la Fuente, Deena Iskander, Lawrence Wolfe, Johnson M Liu, Akiko Shimamura, Katarzyna Albrecht, Birgitte Lausen, Anne Grete Bechensteen, Ulf Tedgard, Alexander Puzik, Paola Quarello, Ugo Ramenghi, Marije Bartels, Heinz Hengartner, Roula A Farah, Mahasen Al Saleh, Amir Ali Hamidieh, Wan Yang, Etsuro Ito, Hoon Kook, Galina Ovsyannikova, Leo Kager, Pierre-Emmanuel Gleizes, Jean-Hugues Dalle, Brigitte Strahm, Charlotte M Niemeyer, Jeffrey M Lipton, Thierry M Leblanc
{"title":"Diagnosis, treatment, and surveillance of Diamond-Blackfan anaemia syndrome: international consensus statement.","authors":"Marcin W Wlodarski, Adrianna Vlachos, Jason E Farrar, Lydie M Da Costa, Antonis Kattamis, Irma Dianzani, Cristina Belendez, Sule Unal, Hannah Tamary, Ramune Pasauliene, Dagmar Pospisilova, Josu de la Fuente, Deena Iskander, Lawrence Wolfe, Johnson M Liu, Akiko Shimamura, Katarzyna Albrecht, Birgitte Lausen, Anne Grete Bechensteen, Ulf Tedgard, Alexander Puzik, Paola Quarello, Ugo Ramenghi, Marije Bartels, Heinz Hengartner, Roula A Farah, Mahasen Al Saleh, Amir Ali Hamidieh, Wan Yang, Etsuro Ito, Hoon Kook, Galina Ovsyannikova, Leo Kager, Pierre-Emmanuel Gleizes, Jean-Hugues Dalle, Brigitte Strahm, Charlotte M Niemeyer, Jeffrey M Lipton, Thierry M Leblanc","doi":"10.1016/S2352-3026(24)00063-2","DOIUrl":"10.1016/S2352-3026(24)00063-2","url":null,"abstract":"<p><p>Diamond-Blackfan anaemia (DBA), first described over 80 years ago, is a congenital disorder of erythropoiesis with a predilection for birth defects and cancer. Despite scientific advances, this chronic, debilitating, and life-limiting disorder continues to cause a substantial physical, psychological, and financial toll on patients and their families. The highly complex medical needs of affected patients require specialised expertise and multidisciplinary care. However, gaps remain in effectively bridging scientific discoveries to clinical practice and disseminating the latest knowledge and best practices to providers. Following the publication of the first international consensus in 2008, advances in our understanding of the genetics, natural history, and clinical management of DBA have strongly supported the need for new consensus recommendations. In 2014 in Freiburg, Germany, a panel of 53 experts including clinicians, diagnosticians, and researchers from 27 countries convened. With support from patient advocates, the panel met repeatedly over subsequent years, engaging in ongoing discussions. These meetings led to the development of new consensus recommendations in 2024, replacing the previous guidelines. To account for the diverse phenotypes including presentation without anaemia, the panel agreed to adopt the term DBA syndrome. We propose new simplified diagnostic criteria, describe the genetics of DBA syndrome and its phenocopies, and introduce major changes in therapeutic standards. These changes include lowering the prednisone maintenance dose to maximum 0·3 mg/kg per day, raising the pre-transfusion haemoglobin to 9-10 g/dL independent of age, recommending early aggressive chelation, broadening indications for haematopoietic stem-cell transplantation, and recommending systematic clinical surveillance including early colorectal cancer screening. In summary, the current practice guidelines standardise the diagnostics, treatment, and long-term surveillance of patients with DBA syndrome of all ages worldwide.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 5","pages":"e368-e382"},"PeriodicalIF":15.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872138","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}
引用次数: 0
Diversity, equity, and inclusion in ASH guidelines - Authors' reply. ASH指南中的多样性、公平性和包容性--作者回复。
IF 15.4 1区 医学
Lancet Haematology Pub Date : 2024-05-01 DOI: 10.1016/S2352-3026(24)00100-5
Jeremy W Jacobs, Garrett S Booth, Julie K Silver
{"title":"Diversity, equity, and inclusion in ASH guidelines - Authors' reply.","authors":"Jeremy W Jacobs, Garrett S Booth, Julie K Silver","doi":"10.1016/S2352-3026(24)00100-5","DOIUrl":"10.1016/S2352-3026(24)00100-5","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 5","pages":"e317-e318"},"PeriodicalIF":15.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873773","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}
引用次数: 0
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