The Lancet Haematology最新文献

{"title":"Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation","authors":"Olaf Penack, Monia Marchetti, Mahmoud Aljurf, Mutlu Arat, Francesca Bonifazi, Rafael F Duarte, Sebastian Giebel, Hildegard Greinix, Mette D Hazenberg, Nicolaus Kröger, Stephan Mielke, Mohamad Mohty, Arnon Nagler, Jakob Passweg, Francesca Patriarca, Tapani Ruutu, Hélène Schoemans, Carlos Solano, Radovan Vrhovac, Daniel Wolff, Zinaida Peric","doi":"10.1016/s2352-3026(23)00342-3","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00342-3","url":null,"abstract":"<p>Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic haematopoietic stem-cell transplantation (HSCT). In the last 3 years, there has been regulatory approval of new drugs<span><span> and considerable change in clinical approaches<span> to prophylaxis and management of GVHD. To standardise treatment approaches, the European Society for Blood and Marrow Transplantation (EBMT) has updated its clinical practice recommendations. We formed a panel of one methodologist and 22 experts in the field of GVHD management. The selection was made on the basis of their role in GVHD management in Europe and their contributions to the field, such as publications, presentations at conferences, and other research. We applied the GRADE process to ten PICO (patient, intervention, comparator, and outcome) questions: evidence was searched for by the panel and graded for each crucial outcome. In two consensus meetings, we discussed the evidence and voted on the wording and strengths of recommendations. Key updates to the recommendations include: (1) primary use of </span></span>ruxolitinib<span><span> in steroid-refractory acute GVHD<span> and steroid-refractory chronic GVHD as the new standard of care, (2) use of rabbit anti-T-cell (thymocyte) </span></span>globulin<span> or post-transplantation cyclophosphamide as standard GVHD prophylaxis in peripheral blood stem-cell transplantations from unrelated donors, and (3) the addition of belumosudil to the available treatment options for steroid-refractory chronic GVHD. The EBMT proposes to use these recommendations as the basis for routine management of GVHD during allogenic HSCT. The current recommendations favour European practice and do not necessarily represent global preferences.</span></span></span></p>","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139091946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extended duration of letermovir prophylaxis: how long is long enough?","authors":"Abby P Douglas, Monica A Slavin","doi":"10.1016/s2352-3026(23)00368-x","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00368-x","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138840019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","authors":"Domenico Russo, Michael Schmitt, Sylvain Pilorge, Matthias Stelljes, Toshiro Kawakita, Valerie L Teal, Barbara Haber, Charlene Bopp, Sanjeet S Dadwal, Cyrus Badshah","doi":"10.1016/s2352-3026(23)00344-7","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00344-7","url":null,"abstract":"<h3>Background</h3><p>In a pivotal phase 3 trial of cytomegalovirus<span><span><span> prophylaxis with letermovir for up to 100 days after allogeneic haematopoietic stem-cell transplantation (HSCT), 12% of participants developed clinically significant </span>cytomegalovirus infection<span><span> after letermovir was discontinued. We aimed to evaluate the efficacy and safety of extending the duration of letermovir prophylaxis for clinically significant </span>cytomegalovirus infection from 100 days to 200 days following </span></span>HSCT.</span></p><h3>Methods</h3><p><span><span><span>We conducted a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 32 sites in six countries (France, Germany, Italy, Japan, the UK, and the USA). Cytomegalovirus‑seropositive HSCT<span> recipients (aged ≥18 years) who had received letermovir prophylaxis for up to 100 days following HSCT and who remained at high risk of late clinically significant cytomegalovirus infection (with no previous history of clinically significant cytomegalovirus infection, defined as initiation of pre-emptive therapy for documented cytomegalovirus </span></span>viraemia, onset of cytomegalovirus end-organ disease, or both) were eligible. Participants were randomly assigned (2:1) to receive either an additional 100 days (ie, a total of 200 days; letermovir group) of oral or intravenous letermovir 480 mg once daily, adjusted to 240 mg once daily for participants on </span>cyclosporin A<span>, or 100 days of a placebo comparator for letermovir (ie, a total of 100 days of letermovir; placebo group), following HSCT. Randomisation was done using a central interactive response technology system, stratified by study centre and haploidentical donor (yes or no). Participants, investigators, and sponsor personnel were masked to the treatment allocation. The primary efficacy endpoint was the proportion of participants from randomisation to week 28 (200 days after HSCT) with clinically significant cytomegalovirus infection, analysed using the full analysis set population (ie, those who received at least one dose of study intervention). Safety was analysed in all participants as treated (ie, those who received at least one dose according to the study intervention they were assigned to). This study is registered with </span></span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"8px\" viewbox=\"0 0 8 8\" width=\"8px\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg>, <span>NCT03930615</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"8px\" viewbox=\"0 0 8 8\" width=\"8px\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg>, and is complete.</p><h3>Findings</h3><p>Between June 21, 2019, and March 16, 2022, 255 patients were screened for eligibility and 220 (86%) were randomly assigned (145 [66%] in the","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138840637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dawn of the CRISPR/Cas9 gene therapy era","authors":"","doi":"10.1016/s2352-3026(23)00372-1","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00372-1","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"198 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting cytopenias, progression, and survival in patients with clonal cytopenia of undetermined significance: a prospective cohort study","authors":"Catherine Cargo, Elsa Bernard, Tumas Beinortas, Kelly L Bolton, Paul Glover, Helen Warren, Daniel Payne, Rukhsaar Ali, Alesia Khan, Mike Short, Suzan Van Hoppe, Alex Smith, Jan Taylor, Paul Evans, Elli Papaemmanuil, Simon Crouch","doi":"10.1016/s2352-3026(23)00340-x","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00340-x","url":null,"abstract":"<h3>Background</h3><p><span><span>Somatic mutations are frequently reported in individuals with </span>cytopenia but without a confirmed haematological diagnosis (clonal cytopenia of undetermined significance; CCUS). These patients have an increased risk of progression to a </span>myeloid malignancy and worse overall survival than those with no such mutations. To date, studies have been limited by retrospective analysis or small patient numbers. We aimed to establish the natural history of CCUS by prospectively investigating outcome in a large, well defined patient cohort.</p><h3>Methods</h3><p><span>This prospective cohort study was conducted at the </span>Haematological Malignancy<span> Diagnostic Service, a diagnostic laboratory in Leeds, UK. Patients aged at least 18 years who were referred for investigation of cytopenia were eligible for inclusion; those with a history of myeloid malignancy were not eligible. Targeted sequencing was conducted alongside routine clinical testing. Baseline mutation analysis was then correlated with the main study outcomes: longitudinal blood counts, disease progression to a myeloid malignancy, and overall survival with a median follow-up of 4·54 years (IQR 4·03–5·04). Data were collected manually from hospital records or extracted from laboratory or clinical outcome databases.</span></p><h3>Findings</h3><p><span>Bone marrow samples from 2348 patients were received at the Haematological Malignancy Diagnostic Service between July 1, 2014, and July 31, 2016. Of these, 2083 patients (median age 72 years [IQR 63–80, range 18–99]; 854 [41·0%] female and 1229 [59·0%] male) met the inclusion criteria and had samples of sufficient quality for further analysis. 598 (28·7%) patients received a diagnosis on the basis of their biopsy sample, whereas 1485 (71·3%) samples were classified as non-diagnostic; of these, CCUS was confirmed in 400 (26·9%) patients (256 [64·0%] male and 144 [36·0%] female). </span><em>TET2, SRSF2,</em> and <span><em>DNMT3A</em></span><span> were the most frequently mutated genes in patients with CCUS, with 320 (80%) of 400 patients harbouring a mutation in at least one of these genes. Age (p&lt;0·0001), sex (p=0·0027), and mutations in </span><span><em>ASXL1</em></span> (p=0·0009), <em>BCOR</em> (p=0·0056), and <em>TP53</em> (p=0·0055) correlated with a worse overall survival; however, the number of mutations was the strongest predictor for progression to a myeloid malignancy (two mutations, p=0·0024; three or more mutations, p=0·0004). Extended sequencing of samples from a subgroup of patients with sequential samples and no mutations in the initial myeloid gene panel showed recurrent mutations in both <em>DDX41</em> and <em>UBA1</em>, suggesting that these genes should be included in clinical test panels.</p><h3>Interpretation</h3><p>Mutation analysis is advised in patients who have undergone bone marrow examination and have an otherwise-unexplained cytopenia. High-risk genetic mutations and increa","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138840147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive view of pregnancy in patients with sickle cell disease in high-income countries: the need for robust data and further decline in morbidity and mortality","authors":"Laure Joseph, Marine Driessen","doi":"10.1016/s2352-3026(23)00310-1","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00310-1","url":null,"abstract":"<p><span>Sickle cell disease is a major </span>public health<span><span> concern due to its prevalence and associated morbidities. In high-income countries, diagnosis and treatment advancements have extended patient's lives and enabled women to embrace motherhood. Although the provision of care in specialist centres has reduced maternal–fetal complication rates, the mortality rate among pregnant women with sickle cell disease remains disproportionately high. Complications arise from vaso-occlusive events, worsening organ damage, thrombotic risks, infections, and pregnancy-related issues, such as pre-eclampsia, premature birth, small-for-gestational-age, and pregnancy loss. Effective management during pregnancy includes preconception planning, genetic counselling, education, and collaborative care. There is no consensus on the overall approach to managing pregnant women with sickle cell disease; however, fostering a collaborative relationship between health-care professionals and researchers is crucial for advancing the understanding and management of this illness. The </span>disparities in health-care outcomes associated with ethnicity and economic insecurity affect patients with sickle cell disease but have not been examined extensively. Hence, health-care personnel need sufficient training to address these issues alongside broader societal efforts to confront racism and discrimination. Comprehensive national and global action plans are required to address the multifaceted challenges of sickle cell disease.</span></p>","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lucrèce Delicat-Loembet: offering hope to young people with sickle cell disease","authors":"Tony Kirby","doi":"10.1016/s2352-3026(23)00374-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00374-5","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting the progression of patients with CCUS to myeloid neoplasia","authors":"Emma M Groarke","doi":"10.1016/s2352-3026(23)00361-7","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00361-7","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Lancet Haematol 2023; 10: e713–34","authors":"","doi":"10.1016/s2352-3026(23)00373-3","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00373-3","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138840614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral decitabine–cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study","authors":"Guillermo Garcia-Manero, James McCloskey, Elizabeth A Griffiths, Karen W L Yee, Amer M Zeidan, Aref Al-Kali, H Joachim Deeg, Prapti A Patel, Mitchell Sabloff, Mary-Margaret Keating, Nancy Zhu, Nashat Y Gabrail, Salman Fazal, Joseph Maly, Olatoyosi Odenike, Hagop Kantarjian, Amy E DeZern, Casey L O’Connell, Gail J Roboz, Lambert Busque, Michael R Savona","doi":"10.1016/s2352-3026(23)00338-1","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00338-1","url":null,"abstract":"<h3>Background</h3><p><span><span>The DNA methyltransferase inhibitors </span>azacitidine and </span>decitabine<span><span><span> for individuals with myelodysplastic syndromes or chronic myelomonocytic leukaemia are available in parenteral form. Oral therapy with similar exposure for these diseases would offer potential treatment benefits. We aimed to compare the safety and </span>pharmacokinetics of oral decitabine plus the </span>cytidine deaminase<span> inhibitor cedazuridine versus intravenous decitabine.</span></span></p><h3>Methods</h3><p><span>We did a registrational, multicentre, open-label, crossover, phase 3 trial of individuals with myelodysplastic syndromes or chronic myelomonocytic leukaemia and individuals with acute myeloid leukaemia<span>, enrolled as separate cohorts; results for only participants with myelodysplastic syndromes or chronic myelomonocytic leukaemia are reported here. In 37 academic and community-based clinics in Canada and the USA, we enrolled individuals aged 18 years or older who were candidates to receive intravenous decitabine, with Eastern Cooperative Oncology Group performance status 0 or 1 and a life expectancy of at least 3 months. Participants were randomly assigned (1:1) to receive 5 days of oral decitabine–cedazuridine (one tablet once daily containing 35 mg decitabine and 100 mg cedazuridine as a fixed-dose combination) or intravenous decitabine (20 mg/m</span></span>² per day by continuous 1-h intravenous infusion) in a 28-day treatment cycle, followed by 5 days of the other formulation in the next treatment cycle. Thereafter, all participants received oral decitabine–cedazuridine from the third cycle on until treatment discontinuation. The primary endpoint was total decitabine exposure over 5 days with oral decitabine–cedazuridine versus intravenous decitabine for cycles 1 and 2, measured as area under the curve in participants who received the full treatment dose in cycles 1 and 2 and had decitabine daily AUC_0–24 for both oral decitabine–cedazuridine and intravenous decitabine (ie, paired cycles). On completion of the study, all patients were rolled over to a maintenance study. This study is registered with <span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"8px\" viewbox=\"0 0 8 8\" width=\"8px\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg>, <span>NCT03306264</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"8px\" viewbox=\"0 0 8 8\" width=\"8px\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg>.</p><h3>Findings</h3><p>Between Feb 8, 2018, and June 7, 2021, 173 individuals were screened, 138 (80%) participants were randomly assigned to a treatment sequence, and 133 (96%) participants (87 [65%] men and 46 [35%] women; 121 [91%] White, four [3%] Black or African-American, three [2%] Asian, and fiv","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}