Lancet Haematology最新文献

{"title":"Time to optimise management of haemolytic disease of the fetus and newborn.","authors":"Jennifer Andrews, Matthew R Grace","doi":"10.1016/S2352-3026(24)00337-5","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00337-5","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":15.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631181","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":15.4,"publicationDate":"2024-11-08","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":15.4,"publicationDate":"2024-11-06","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}

{"title":"Accelerating and optimising CAR T-cell manufacture to deliver better patient products.","authors":"Giulia Agliardi, Juliana Dias, Alexandros Rampotas, John Garcia, Claire Roddie","doi":"10.1016/S2352-3026(24)00273-4","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00273-4","url":null,"abstract":"<p><p>Autologous chimeric antigen receptor (CAR) T-cell therapy has transformed the management of B-cell leukaemia and lymphoma. However, current manufacturing processes present logistical hurdles, restricting broader application. As clinical outcomes can be heavily influenced by the quality of autologous starting materials and production processes, strategies to improve product phenotype are crucial. Short manufacturing processes have the advantage of bringing products to patients more quickly and, in parallel, avoiding the highly differentiated and exhausted CAR T-cell phenotypes associated with prolonged ex vivo manufacture. This Review examines advances in our understanding of what constitutes an effective CAR T-cell product and approaches to improve product quality. Historically, strategies have relied on adjustments in medium composition and selection of less differentiated cell subtypes. Since 2020, the field has been shifting towards reduced-expansion protocols, no-activation protocols, and point-of-care manufacturing. These approaches have the advantage of a rapid turnaround while maintaining a less differentiated and exhausted phenotype. These efforts are leading to ultrarapid production methods and even elimination of ex vivo manipulation with the use of in vivo manufacturing approaches. In this Review, we focus on the advances needed to accelerate CAR T-cell manufacture (including near-patient methods), with an emphasis on improved therapeutic efficacy and rapid turnaround time, and simplified quality control procedures required to fully realise the clinical potential of CAR T-cell therapies.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":15.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607025","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}

{"title":"Iron deficiency as a marker of inequality.","authors":"The Lancet Haematology","doi":"10.1016/S2352-3026(24)00318-1","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00318-1","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 11","pages":"e803"},"PeriodicalIF":15.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559173","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}

{"title":"The Global Fund should extend its mandate to include universal access to hydroxyurea.","authors":"Isaac Odame, Lêon Tshilolo, Julie Makani, Obiageli Nnodu, Adekunle Adekile, Baba Inusa","doi":"10.1016/S2352-3026(24)00275-8","DOIUrl":"10.1016/S2352-3026(24)00275-8","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e810-e811"},"PeriodicalIF":15.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382088","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}

{"title":"Venetoclax plus decitabine as a bridge to allogeneic haematopoietic stem-cell transplantation in older patients with acute myeloid leukaemia (VEN-DEC GITMO): final report of a multicentre, single-arm, phase 2 trial.","authors":"Domenico Russo, Nicola Polverelli, Simona Bernardi, Stella Santarone, Mirko Farina, Erika Borlenghi, Francesco Onida, Luca Castagna, Stefania Bramanti, Angelo Michele Carella, Roberto Sorasio, Massimo Martino, Caterina Alati, Attilio Olivieri, Germana Beltrami, Antonio Curti, Calogero Vetro, Salvatore Leotta, Valentina Mancini, Elisabetta Terruzzi, Massimo Bernardi, Piero Galieni, Pellegrino Musto, Raffaella Cerretti, Luisa Giaccone, Cristina Skert, Vera Radici, Marika Vezzoli, Stefano Calza, Alessandro Leoni, Luca Garuffo, Cristian Bonvicini, Simone Pellizzeri, Michele Malagola, Fabio Ciceri","doi":"10.1016/S2352-3026(24)00241-2","DOIUrl":"10.1016/S2352-3026(24)00241-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Access to allogeneic haematopoietic stem-cell transplantation (HSCT) remains challenging for older patients (aged &gt;60 years) with acute myeloid leukaemia. We aimed to evaluate the efficacy of venetoclax plus decitabine as first-line therapy and bridge to transplantation in this patient population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This multicentre, single-arm, phase 2 trial was conducted in 20 Gruppo Italiano Trapianto Midollo Osseo (GITMO) centres in Italy. Patients aged ≥60 and &lt;75 years, with newly diagnosed acute myeloid leukaemia categorised as intermediate or high risk according to 2016 WHO and 2017 European LeukemiaNet, an ECOG performance status of less than 2, and considered fit for allogeneic HSCT were included. Patients received oral venetoclax with a 3-day ramp-up: 100 mg on day 1, 200 mg on day 2, and 400 mg once per day from day 3 of cycle one, and then every 28 days of each cycle (two to four in total). Decitabine was administered intravenously at a dose of 20 mg/m&lt;sup&gt;2&lt;/sup&gt; from days 1 to 5 every 28 days. At cycle one, patients were admitted to hospital for a minimum of 24 h, whereas subsequent cycles could be administered on an outpatient basis. Two additional cycles were allowed while waiting for allogeneic HSCT or for those with no response or partial response after cycle two. The primary endpoint was the proportion of patients who had allogeneic HSCT performed during first complete remission, assessed in all patients who received at least one dose of the study medication. This study was registered with ClinicalTrials.gov (NCT04476199, ongoing) and EudraCT (2020-002297-26).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between June 1, 2021, and Dec 30, 2022, 93 patients were enrolled and started venetoclax plus decitabine induction (44 [47%] at intermediate risk and 49 [53%] at high risk). The median age was 68·5 (IQR 60·3-74·7). All 93 participants were White, of whom 43 (46%) were female and 50 (54%) were male. The median follow-up was 236 days (IQR 121-506). 64 (69%) of 93 patients reached complete remission and 53 (57%) underwent allogeneic HSCT in complete remission. 53 (83%) of 64 with a complete remission underwent allogeneic HSCT. Five (8%) of 64 patients in complete remission relapsed before transplantation and four died as a consequence. Adverse events (grade ≥3) occurred in 49 (53%) of 93 patients. The most common adverse events were infections (including pneumonia, bacterial sepsis, and SARS-CoV-2 causing seven deaths among 28 [57%] of 49 patients), neutropenia (17 [35%]), thrombocytopenia (two [4%], including one fatal CNS bleeding), and cardiac events (four [8%], including one fatal heart failure). No treatment-related deaths were observed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Venetoclax plus decitabine induction can significantly enhance the feasibility of allogeneic HSCT in older patients with acute myeloid leukaemia who are deemed fit for transplantation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;Abb","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e830-e838"},"PeriodicalIF":15.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308821","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}

{"title":"Transplantation and long-term overall survival in acute myeloid leukaemia.","authors":"Maria A Perusini, Karen W L Yee","doi":"10.1016/S2352-3026(24)00274-6","DOIUrl":"10.1016/S2352-3026(24)00274-6","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e805-e806"},"PeriodicalIF":15.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308820","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}

{"title":"Management of pregnancies with anti-K alloantibodies and the predictive value of anti-K titration testing.","authors":"Evangelia Vlachodimitropoulou, Nadine Shehata, Greg Ryan, Gwen Clarke, Lani Lieberman","doi":"10.1016/S2352-3026(24)00239-4","DOIUrl":"10.1016/S2352-3026(24)00239-4","url":null,"abstract":"<p><p>Anti-KEL1 antigen (also referred to as anti-Kell, or anti-K) alloimmunisation is the second most common cause of severe haemolytic disease of the fetus and newborn, after anti-rhesus D antigen, and can cause substantial fetal morbidity and mortality. Both fetal erythropoietic suppression and haemolysis contribute to anaemia. Typically, once a clinically significant alloantibody is identified during pregnancy, antibody titration is performed as a screening test to predict the risk of anaemia and the need for maternal-fetal medicine referral. The titre is a semiquantitative laboratory method based on the underlying principle that increased maternal antibody concentrations are associated with an increased risk of fetal anaemia. Because some studies report that anti-K alloantibodies can lead to severe anaemia even at a low antibody titration, guidelines are inconsistent with respect to the role of titration testing. Some experts recommend maternal-fetal medicine referral and middle cerebral artery Doppler ultrasound without titration testing or with the use of a very low cutoff titre. This Viewpoint evaluates management for pregnancies affected by anti-K alloantibodies and highlights literature regarding the predictive value of anti-K titration testing.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e873-e877"},"PeriodicalIF":15.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113760","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}

{"title":"Data-driven, harmonised classification system for myelodysplastic syndromes: a consensus paper from the International Consortium for Myelodysplastic Syndromes.","authors":"Rami S Komrokji, Luca Lanino, Somedeb Ball, Jan P Bewersdorf, Monia Marchetti, Giulia Maggioni, Erica Travaglino, Najla H Al Ali, Pierre Fenaux, Uwe Platzbecker, Valeria Santini, Maria Diez-Campelo, Avani Singh, Akriti G Jain, Luis E Aguirre, Sarah M Tinsley-Vance, Zaker I Schwabkey, Onyee Chan, Zhouer Xie, Andrew M Brunner, Andrew T Kuykendall, John M Bennett, Rena Buckstein, Rafael Bejar, Hetty E Carraway, Amy E DeZern, Elizabeth A Griffiths, Stephanie Halene, Robert P Hasserjian, Jeffrey Lancet, Alan F List, Sanam Loghavi, Olatoyosi Odenike, Eric Padron, Mrinal M Patnaik, Gail J Roboz, Maximilian Stahl, Mikkael A Sekeres, David P Steensma, Michael R Savona, Justin Taylor, Mina L Xu, Kendra Sweet, David A Sallman, Stephen D Nimer, Christopher S Hourigan, Andrew H Wei, Elisabetta Sauta, Saverio D'Amico, Gianluca Asti, Gastone Castellani, Mattia Delleani, Alessia Campagna, Uma M Borate, Guillermo Sanz, Fabio Efficace, Steven D Gore, Tae Kon Kim, Navel Daver, Guillermo Garcia-Manero, Maria Rozman, Alberto Orfao, Sa A Wang, M Kathryn Foucar, Ulrich Germing, Torsten Haferlach, Phillip Scheinberg, Yasushi Miyazaki, Marcelo Iastrebner, Austin Kulasekararaj, Thomas Cluzeau, Shahram Kordasti, Arjan A van de Loosdrecht, Lionel Ades, Amer M Zeidan, Matteo G Della Porta","doi":"10.1016/S2352-3026(24)00251-5","DOIUrl":"10.1016/S2352-3026(24)00251-5","url":null,"abstract":"<p><p>The WHO and International Consensus Classification 2022 classifications of myelodysplastic syndromes enhance diagnostic precision and refine decision-making processes in these diseases. However, some discrepancies still exist and potentially cause inconsistency in their adoption in a clinical setting. We adopted a data-driven approach to provide a harmonisation between these two classification systems. We investigated the importance of genomic features and their effect on the cluster assignment process to define harmonised entity labels. A panel of expert haematologists, haematopathologists, and data scientists who are members of the International Consortium for Myelodysplastic Syndromes was formed and a modified Delphi consensus process was adopted to harmonise morphologically defined categories without a distinct genomic profile. The panel held regular online meetings and participated in a two-round survey using an online voting tool. We identified nine clusters with distinct genomic features. The cluster of highest hierarchical importance was characterised by biallelic TP53 inactivation. Cluster assignment was irrespective of blast count. Individuals with monoallelic TP53 inactivation were assigned to other clusters. Hierarchically, the second most important group included myelodysplastic syndromes with del(5q). Isolated del(5q) and less than 5% of blast cells in the bone marrow were the most relevant label-defining features. The third most important cluster included myelodysplastic syndromes with mutated SF3B1. The absence of isolated del(5q), del(7q)/-7, abn3q26.2, complex karyotype, RUNX1 mutations, or biallelic TP53 were the basis for a harmonised label of this category. Morphologically defined myelodysplastic syndrome entities showed large genomic heterogeneity that was not efficiently captured by single-lineage versus multilineage dysplasia, marrow blasts, hypocellularity, or fibrosis. We investigated the biological continuum between myelodysplastic syndromes with more than 10% bone marrow blasts and acute myeloid leukaemia, and found only a partial overlap in genetic features. After the survey, myelodysplastic syndromes with low blasts (ie, less than 5%) and myelodysplastic syndromes with increased blasts (ie, 5% or more) were recognised as disease entities. Our data-driven approach can efficiently harmonise current classifications of myelodysplastic syndromes and provide a reference for patient management in a real-world setting.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e862-e872"},"PeriodicalIF":15.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407071","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}