{"title":"Oral decitabine plus cedazuridine versus intravenous decitabine","authors":"Theo de Witte","doi":"10.1016/s2352-3026(23)00363-0","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00363-0","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770461","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":"Changing the paradigm of AML care in India","authors":"Amitabh Singh, Ankur Jain, Heena Tabbassum, Fouzia Siraj, Bhavika Rishi, Aroonima Misra","doi":"10.1016/s2352-3026(23)00360-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00360-5","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770411","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":"Is there a path forward for immunotherapy in patients with myelodysplastic syndromes?","authors":"Maximilian Stahl, Amy E DeZern","doi":"10.1016/s2352-3026(23)00343-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00343-5","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":" 54","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138485790","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}
Amer M Zeidan, Kiyoshi Ando, Odile Rauzy, Mehmet Turgut, Ming-Chung Wang, Roberto Cairoli, Hsin-An Hou, Yok-Lam Kwong, Montserrat Arnan, Stef Meers, Vinod Pullarkat, Valeria Santini, Kamel Malek, Flavia Kiertsman, Julie Niolat, Pedro Marques Ramos, Hans D Menssen, Pierre Fenaux, Yasushi Miyazaki, Uwe Platzbecker
{"title":"Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial","authors":"Amer M Zeidan, Kiyoshi Ando, Odile Rauzy, Mehmet Turgut, Ming-Chung Wang, Roberto Cairoli, Hsin-An Hou, Yok-Lam Kwong, Montserrat Arnan, Stef Meers, Vinod Pullarkat, Valeria Santini, Kamel Malek, Flavia Kiertsman, Julie Niolat, Pedro Marques Ramos, Hans D Menssen, Pierre Fenaux, Yasushi Miyazaki, Uwe Platzbecker","doi":"10.1016/s2352-3026(23)00333-2","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00333-2","url":null,"abstract":"<h3>Background</h3><p><span>Sabatolimab is an immunotherapy targeting T-cell </span>immunoglobulin domain<span> and mucin domain-3 (TIM-3), an immuno-myeloid regulator expressed on immune cells<span> and leukaemic stem cells. In this trial, we compared the efficacy and safety of sabatolimab plus hypomethylating agent with placebo plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes.</span></span></p><h3>Methods</h3><p><span><span><span>STIMULUS-MDS1 was a multicentre, randomised, double-blind, placebo-controlled, phase 2 study done at 54 investigational sites in 17 countries. Adult patients (aged ≥18 years) with intermediate-risk, high-risk, and very high-risk myelodysplastic syndromes (according to Revised International Prognostic Scoring System criteria) who had not received previous </span>treatment were included. Patients were randomly assigned (1:1) to intravenous sabatolimab (400 mg on day 8 and 22) or placebo plus a hypomethylating agent (intravenous </span>decitabine 20 mg/m</span><sup>2</sup><span> on day 1–5 or intravenous or subcutaneous azacitidine 75 mg/m</span><sup>2</sup> on day 1–7 or day 1–5 and day 8 and 9) every 28 days until treatment discontinuation. The two primary endpoints were complete response rate and progression-free survival, assessed in the full analysis set, which included all randomly assigned patients. Complete response was analysed, as prespecified, 7 months after the last patient was randomly assigned. All other analyses presented, including progression-free survival, were done at the final data cutoff prespecified via a protocol amendment on Sept 2, 2021. Safety was assessed in in all patients who received at least one dose of study treatment. 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>NCT03946670</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 ongoing.</p><h3>Findings</h3><p>Between July 29, 2019, and Aug 10, 2020, 127 patients were randomly assigned to sabatolimab plus a hypomethylating agent group (sabatolimab group; n=65) or placebo plus a hypomethylating agent (placebo group; n=62). The median age of participants was 73 years (IQR 69–77), of whom 86 (68%) of 127 patients were male and 77 (61%) were White. The primary endpoints were not met. Complete response (cutoff date of March 10, 2021) was achieved in 14 (22%; 95% CI 12·3–33·5) of 65 patients in the sabatolimab group <em>vs</em> 11 (18%; 9·2–29·5) of 62 patients in the placebo group (p=0·77). At the cutoff date of the final analysis (March 1, 2022), median follow-up for progression-free survival","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":" 47","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138485794","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}
Nicolaus Kröger, Andrea Bacigalupo, Tiziano Barbui, Markus Ditschkowski, Nico Gagelmann, Martin Griesshammer, Vikas Gupta, Nada Hamad, Claire Harrison, Juan Carlos Hernandez-Boluda, Steffen Koschmieder, Tania Jain, John Mascarenhas, Ruben Mesa, Uday R Popat, Francesco Passamonti, Nicola Polverelli, Alessandro Rambaldi, Marie Robin, Rachel B Salit, Giovanni Barosi
{"title":"Indication and management of allogeneic haematopoietic stem-cell transplantation in myelofibrosis: updated recommendations by the EBMT/ELN International Working Group","authors":"Nicolaus Kröger, Andrea Bacigalupo, Tiziano Barbui, Markus Ditschkowski, Nico Gagelmann, Martin Griesshammer, Vikas Gupta, Nada Hamad, Claire Harrison, Juan Carlos Hernandez-Boluda, Steffen Koschmieder, Tania Jain, John Mascarenhas, Ruben Mesa, Uday R Popat, Francesco Passamonti, Nicola Polverelli, Alessandro Rambaldi, Marie Robin, Rachel B Salit, Giovanni Barosi","doi":"10.1016/s2352-3026(23)00305-8","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00305-8","url":null,"abstract":"<p><span>New options for medical therapy and risk scoring systems containing molecular data are leading to increased complexity in the management of patients with myelofibrosis<span>. To inform patients’ optimal care, we updated the 2015 guidelines on indications for and management of allogeneic haematopoietic stem-cell transplantation (HSCT) with the support of the European Society for Blood and Marrow Transplantation (EBMT) and European LeukemiaNet (ELN). New recommendations were produced using a consensus-building methodology after a comprehensive review of articles released from January, 2015 to December, 2022. Seven domains and 18 key questions were selected through a series of questionnaires using a Delphi process. Key recommendations in this update include: patients with primary myelofibrosis and an intermediate-2 or high-risk Dynamic </span></span>International Prognostic Scoring System<span> score, or a high-risk Mutation-Enhanced International Prognostic Score Systems (MIPSS70 or MIPSS70-plus) score, or a low-risk or intermediate-risk Myelofibrosis Transplant Scoring System score should be considered candidates for allogeneic HSCT. All patients who are candidates for allogeneic HSCT with splenomegaly<span><span> greater than 5 cm below the left costal margin or splenomegaly-related symptoms should receive a spleen-directed treatment, ideally with a JAK-inhibitor; HLA-matched sibling donors remain the preferred donor source to date. </span>Reduced intensity conditioning<span> and myeloablative conditioning<span> are both valid options for patients with myelofibrosis. Regular post-transplantation driver mutation monitoring is recommended to detect and treat early relapse with donor lymphocyte infusion. In a disease where evidence-based guidance is scarce, these recommendations might help clinicians and patients in shared decision making.</span></span></span></span></p>","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":" 94","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138485747","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}
Jeremy W Jacobs, Brian D Adkins, Deva Sharma, Allison P Wheeler, Laura D Stephens, Jennifer S Woo, Shazia S Khan, Garrett S Booth
{"title":"Assessing authorship of clinical practice guidelines","authors":"Jeremy W Jacobs, Brian D Adkins, Deva Sharma, Allison P Wheeler, Laura D Stephens, Jennifer S Woo, Shazia S Khan, Garrett S Booth","doi":"10.1016/s2352-3026(23)00337-x","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00337-x","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"46 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138455941","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}
Isabelle M C Ree, Masja de Haas, Nan van Geloven, Sandra E Juul, Derek de Winter, E J T Verweij, Dick Oepkes, Johanna G van der Bom, Enrico Lopriore
{"title":"Darbepoetin alfa to reduce transfusion episodes in infants with haemolytic disease of the fetus and newborn who are treated with intrauterine transfusions in the Netherlands: an open-label, single-centre, phase 2, randomised, controlled trial","authors":"Isabelle M C Ree, Masja de Haas, Nan van Geloven, Sandra E Juul, Derek de Winter, E J T Verweij, Dick Oepkes, Johanna G van der Bom, Enrico Lopriore","doi":"10.1016/s2352-3026(23)00285-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00285-5","url":null,"abstract":"<h3>Background</h3><p><span>Up to 88% of infants with haemolytic disease<span><span><span> of the fetus and newborn who are treated with </span>intrauterine transfusions<span> require erythrocyte transfusions after </span></span>birth. We aimed to investigate the effect of </span></span>darbepoetin alfa on the prevention of postnatal anaemia in infants with haemolytic disease of the fetus and newborn.</p><h3>Methods</h3><p><span>We conducted an open-label, single-centre, phase 2 randomised controlled trial<span> to evaluate the effect of darbepoetin alfa on the number of erythrocyte transfusions in infants with haemolytic disease of the fetus and newborn. All infants who were treated with intrauterine transfusion and born at 35 weeks of gestation or later at the Leiden University Medical Center, Leiden, Netherlands, were eligible for inclusion. Included infants were randomised by computer at birth to treatment with 10 μg/kg darbepoetin alfa subcutaneously once a week for 8 weeks or standard care (1:1 allocation, in varying blocks of four and six, with no stratification). Treating physicians and parents were not masked to treatment allocation, but the research team, data manager, and statistician were masked to treatment allocation during the process of data collection. The primary outcome was the number of erythrocyte transfusion episodes per infant from birth up to 3 months of life in the modified intention-to-treat population. This trial 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>NCT03104426</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 has been completed.</p><h3>Findings</h3><p>Between Oct 31, 2017, and April 31, 2022, we recruited 76 infants, of whom 44 (58%) were randomly assigned to a treatment group (20 [45%] were allocated to receive darbepoetin alfa and 24 [55%] were allocated to receive standard care). Follow-up lasted 3 months and one infant dropped out of the trial before commencement of treatment. A significant reduction in erythrocyte transfusion episodes was identified with darbepoetin alfa treatment compared with standard care (median 1·0 [IQR 1·0–2·0] transfusion episodes <em>vs</em> 2·0 [1·3–3·0] transfusion episodes; p=0·0082). No adverse events were reported and no infants died during the study.</p><h3>Interpretation</h3><p>Darbepoetin alfa reduced the transfusion episodes after intrauterine transfusion treatment for haemolytic disease of the fetus and newborn. Treatment with darbepoetin alfa or other types of erythropoietin should be considered as part of the postnatal treatment of severe haemolytic disease of the fe","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138455942","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}