The Lancet Haematology最新文献

{"title":"Anti-GPRC5D CAR T-cell therapy as a salvage treatment in patients with progressive multiple myeloma after anti-BCMA CAR T-cell therapy: a single-centre, single-arm, phase 2 trial.","authors":"Jieyun Xia,Qian Sun,Dian Zhou,Hujun Li,Ying Wang,Yuekun Qi,Jiang Cao,Zhiling Yan,Depeng Li,Hai Cheng,Wei Sang,Feng Zhu,Haiying Sun,Wei Chen,Kunming Qi,Dongmei Yan,Tingting Qiu,Tingyu Hu,Weiying Gu,Jun Qian,Fan Xia,Na Qi,Congqian Jin,Yang Liu,Xue Wang,Yanlei Zhang,Shuixiu Peng,Zhenyu Li,Alex H Chang,Kailin Xu","doi":"10.1016/s2352-3026(25)00048-1","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00048-1","url":null,"abstract":"BACKGROUNDFor patients with multiple myeloma progression after anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, the optimal salvage treatment strategies remain unclear. GPRC5D-directed CAR T cell might be a potential option. The aim of this trial was to investigate the activity and safety of anti-GPRC5D CAR T cells in patients with progressive multiple myeloma after anti-BCMA CAR T-cell therapy.METHODSIn this phase 2, open-label, single-arm, phase 2 trial, at the Affiliated Hospital of Xuzhou Medical University in China, we enrolled patients (aged 18-70 years old) with relapsed or refractory multiple myeloma who had progressed disease after anti-BCMA CAR T-cell therapy and a life expectancy of more than 12 weeks without active infections, serious liver, heart, or other diseases. Patients were assigned to receive a single dose of intravenous anti-GPRC5D CAR T cell at 2 × 106 cells per kg. The primary endpoint was the overall response rate, including stringent complete response, complete response, very good partial response, and partial response, according to the standard International Myeloma Working Group response assessment criteria. Activity and safety analyses were done in the patients who received a dose of anti-GPRC5D CAR T cell as defined in the protocol. This trial is registered with the Chinese Clinical Trial Registration Center, ChiCTR2100048888, and is ongoing.FINDINGSBetween Dec 1, 2021, and May 1, 2024, 42 patients were screened, 37 were enrolled and received anti-GPRC5D CAR T-cell therapy. Median age was 59 years (IQR 51-65), 17 (46%) of 37 patients were male and 20 (54%) female. All patients were Asian. At a median follow-up of 12·6 months (IQR 8·2-20·8), the overall response rate was 84% (95% CI 68-94, 31 of 37 patients), including 13 (35%) complete responses or better. The most common grade 3-4 adverse events were haematological toxicities, including leukopenia (34 [92%] of 37 patients), lymphopenia (36 [97%]), neutropenia (29 [78%]), anaemia (23 [62%]), and thrombocytopenia (23 [62%]). 26 (70%) of 37 patients had cytokine release syndrome, which was of grade 3 in two (5%) patients. One case of grade 1 immune effector cell-associated neurotoxicity syndrome was observed. There were no treatment-related deaths in the trial.INTERPRETATIONAnti-GPRC5D CAR T-cell salvage therapy induced a high response rate, and could be a potential treatment option in relapsed or refractory multiple myeloma patients who have progressed after anti-BCMA CAR T-cell treatment. Further investigations are warranted to establish the long-term efficacy and safety of this therapeutic approach.FUNDINGNational Natural Science Foundation of China and the General Project of Jiangsu Commission of Health.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836509","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":"Sequential CAR T-cell therapy in myeloma: going from BCMA to GPRC5D.","authors":"Niels W C J van de Donk,Carlos Fernandez de Larrea","doi":"10.1016/s2352-3026(25)00074-2","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00074-2","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"294 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836539","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-phase anticoagulant treatment of acute venous thromboembolism in children: a cohort study from the EINSTEIN-Jr phase 3 trial.","authors":"Christoph Male,Anthonie W A Lensing,Anthony K C Chan,Gili Kenet,Guy Young,Rukhmi Bhat,Akos F Pap,Dagmar Kubitza,Martin H Prins,Paul Monagle,","doi":"10.1016/s2352-3026(25)00067-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00067-5","url":null,"abstract":"BACKGROUNDExtended-phase anticoagulation of venous thromboembolism in children is not well documented nor systematically reported. Previously, we reported on recurrent venous thromboembolism and bleeding during acute-phase anticoagulation in EINSTEIN-Jr, a randomised controlled study in 500 children with venous thromboembolism comparing rivaroxaban to standard anticoagulants. The aim of the present study was to evaluate the efficacy and safety of extended-phase anticoagulant therapy in children and to characterise factors associated with the decision to extend anticoagulation.METHODSChildren aged 17 years or younger, who were enrolled in the EINSTEIN-Jr trial (NCT02234843) from 107 paediatric hospitals in 28 countries, and who had previously completed a 3-month acute anticoagulation treatment phase (1-month in children <2 years with catheter-related venous thromboembolism) for acute venous thromboembolism within the trial were included in this cohort study. After completion of the preceding acute anticoagulation treatment phase, children could extend study treatment for up to 9 months (or up to 2 months for children <2 years with catheter-related venous thromboembolism). Study anticoagulants were bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20 mg equivalent dose or standard anticoagulants (heparin or vitamin K antagonist). The main outcomes were suspected recurrent venous thromboembolism (primary efficacy outcome) and clinically relevant bleeding (principal safety outcome), both confirmed or refuted by appropriate objective testing. Cumulative incidences of efficacy and safety outcomes are reported for children who received extended anticoagulation within the framework of the study. We also compared demographic and clinical characteristics of those administered any extended-phase anticoagulation (whether within or outside the framework of the study) with those not administered extended-phase anticoagulation, applying multivariable logistic regression.FINDINGS248 (51%) children received extended-phase anticoagulation between Nov 14, 2014, and Jan 15, 2019, 214 within the study and 34 outside the framework of the study. During extended-phase anticoagulant treatment, recurrent venous thromboembolism occurred in three (1%) of the 214 children within the study (cumulative incidence 3·0%; 95% CI 0·9-9·8). Clinically relevant non-major bleeding occurred in four (2%) of 214 children (3·3%; 1·2-9·2). Fatal venous thromboembolism or major bleeding did not occur. Outcome rates were similar with rivaroxaban or standard anticoagulants. Symptomatic index venous thromboembolism (odds ratio 1·88; 95% CI 1·14-3·11), unprovoked venous thromboembolism or persistent risk factor (2·16; 1·46-3·19), and residual thrombosis on repeat imaging (3·79; 2·52-5·71) were associated with the decision to extend anticoagulation.INTERPRETATIONIncidences of recurrent venous thromboembolism and bleeding during extended-phase anticoagulant treatment were low and simil","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831561","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 it time for a large trial to evaluate aspirin for obstetric venous thromboembolism prophylaxis?","authors":"Alexander M Friedman","doi":"10.1016/s2352-3026(24)00374-0","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00374-0","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991716","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":"Low-dose aspirin versus placebo in postpartum venous thromboembolism: a multi-national, pilot, randomised, placebo-controlled trial.","authors":"Leslie Skeith,A Kinga Malinowski,Darine El-Chaâr,Wee-Shian Chan,Jennifer Donnelly,Céline Chauleur,Wessel Ganzevoort,Stephen Wood,Suzanne Dubois,Claire McCarthy,Andrea Buchmuller,Hanke Wiegers,Paul S Gibson,Fionnuala Ní Áinle,Saskia Middeldorp,Lisa Duffett,Shannon M Bates,Alexandra Garven,Jill Baxter,Brendan Cord Lethebe,Marc A Rodger,","doi":"10.1016/s2352-3026(24)00338-7","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00338-7","url":null,"abstract":"BACKGROUNDDespite the morbidity and mortality of venous thromboembolism, there is little evidence to guide postpartum thromboprophylaxis in patients at moderate risk. We aimed to assess the feasibility of conducting a double-blind, randomised trial of aspirin versus placebo in postpartum individuals with two or more venous thromboembolism risk factors, mild-to-moderate thrombophilia, or both.METHODSThe pilot PARTUM trial, a multi-national, randomised, double-blind, placebo-controlled trial, was conducted in seven centres across Canada, France, Ireland, and the Netherlands. Postpartum individuals aged 18 years or older with venous thromboembolism risk factors, including mild-moderate inherited thrombophilia, antepartum immobilisation, pre-pregnancy BMI of 30 kg/m2 or higher, pre-pregnancy smoking, previous superficial vein thrombosis, and other pregnancy-related conditions, were eligible. Participants were randomly assigned (1:1) within 48 h of delivery to aspirin 81 mg (80 mg in Europe) orally daily (low-dose aspirin group) or placebo orally once daily (placebo group) for 42 days. Follow-up visits occurred at 6 weeks and 90 days postpartum. The primary outcome was the mean recruitment rate (participants per site per month). Additional feasibility metrics were reported, and clinical outcomes were analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT04153760, and EudraCT, 2020-000619-58, and is completed.FINDINGSBetween Nov 2, 2020, and June 19, 2023, 10 040 patients were assessed for eligibility and 808 met all eligibility criteria, of whom 257 (32%) provided consent and were enrolled. 127 were randomly assigned to the low-dose aspirin group and 130 to the placebo group. The median follow-up was 91 days (IQR 89-96). The median age was 34·0 years (IQR 30·0-37·0), and 161 (63%) of participants were White. The mean recruitment rate was 6·3 (95% CI 5·5 to 7·2) patients per site per month. No venous thromboembolism events occurred in the low-dose aspirin group, and one participant had distal deep vein thrombosis in the placebo group (-0·82 [95% CI -2·42 to 0·78]). No major bleeds occurred. Three (2%) participants in the low-dose aspirin group versus one (1%) in the placebo group had clinically relevant non-major bleeds (absolute risk difference 1·66 [95% CI -1·54 to 4·86]). Ten serious adverse events occurred in nine (4%) of 257 participants, and 11 serious adverse events occurred in ten (4%) of 271 infants of participants. No treatment-related death occurred.INTERPRETATIONA global postpartum thromboprophylaxis trial evaluating low-dose aspirin is possible and needed to provide high-quality data.FUNDINGCanadian Institutes of Health Research and the INVENT-VTE Network.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"121 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991714","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":"Antifibrinolytics do not add to the benefits of platelet transfusion","authors":"Charles A Schiffer","doi":"10.1016/s2352-3026(24)00343-0","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00343-0","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790125","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":"Tranexamic acid versus placebo to prevent bleeding in patients with haematological malignancies and severe thrombocytopenia (TREATT): a randomised, double-blind, parallel, phase 3 superiority trial","authors":"TREATT Trial Investigators, Lise J Estcourt, Zoe K McQuilten, Peter Bardy, Merrole Cole-Sinclair, Graham P. Collins, Philip J. Crispin, Elinor Curnow, Jennifer Curnow, Amber Degelia, Claire Dyer, Adam Friebe, Lajos Floro, Effie Grand, Cara Hudson, Gail Jones, Joanne Joseph, Charlotte Kallmeyer, Marina Karakantza, Paul Kerr, Sara Last, Maria Lobo-Clarke, Matthew Lumley, Mary F McMullin, Patrick G. Medd, Suzy M. Morton, Andrew D. Mumford, Maria Mushkbar, Joseph Parsons, Gillian Powter, Mallika Sekhar, Laura Smith, Richard Soutar, William S. Stevenson, Elango Subramoniapillai, Jeff Szer, Helen Thomas, Neil A. Waters, Andrew H. Wei, David A. Westerman, Sarah A. Wexler, Erica M. Wood, Simon J. Stanworth, Adrienne Abioye, Rabia Afghan, Sylvia Ai Ai, Magbor Akanni, Rajesh Alajangi, Usmaan Alam, Bahaa Al-Bubseeree, Sophie Alderson, Craig Alderson, Sayed Ali, Kabir Ali, Rookmeen Alighan, Rebecca Allam Allam, Tania Allen, Wesam Al-Sakkaf, Kate Ames, Jacqueline Anderson, Colin Andrews, Ann-Marie Angel, Manuela Anlya Anlya, Farah Ansari, Rowan Appleby, Claire Arnold, Hulda Asbjornsdottir, Biruk Asfaw, Elissa Atkins, Leela Atkinson, Clare Aubrey, Noor Ayesha, Lola Babbola, David Badcock, Samuel Badcock, Diva Baggio, Ben Bailiff, Kizzy Baines, Holly Baker, Victoria Baker, Lindsay Ball, Martin Ball, Irwin Balquin, Emma Banks, George Banos, Jaytee Barnett, Claire Barrie, Claire Barron, Rebecca Barton, Nina Bason, Bindu Batta, Dianne Bautista, Angela Bayley, Emma Bayly, Fionnuala Baynes, Ali Bazargan, Rachel Bazeley, Yvonne Beadle, Claire Beardsmore, Kate Beattie, Kate Beattie, Caroline Bedford, Rachna Behal, Daniel Behan, Lilihna Bejan, Sarah Bell, Karen Bell, Louise Bell, Kaitlyn Bell, Reuben Benjamin, Sam Bennett, Gary Benson, Warwick Benson, Cameron Bent, Krystal Bergin, Alex Berry, Stephanie Besenyei, Caroline Besley, Scott Betteridge, Leigh Beveridge, Abir Bhattacharyya, Annelies Billen, Ian Bilmon, Emma Binns, Mark Birt, David Bishop, Andrea Blanco, Lisa Bleby, Richard Blemnerhet, Piers Blombery, Emily Blyth, Nicola Blythe, Lauren Boal, Ali Boden, Syed W.I. Bokhari, Elisa Bongetti, Stephen Booth, Jayne Borley, David Bowen, Dawn Bowers, Stephen Boyd, Sarah Bradley, Helen Bradman, Peta Bretag, Maria Brillante, Rachel Brockbank, Yasmin Brough, Ellen Brown, Jo Brown, Eleanor Brown, Claire Brown, Jenny Brown, Susan Brown, Joe Browning, Alex Brownsdon, David Bruce, Ruth Brydon-Hill, Andrea Buckwell, Dannielle Burgess, Glenda Burke, Kate Burley, Claire Burney, David Burns, Samuel Burrows, Kieran burton, Jason Butler, Lenka Cambalova, Maria C. Camozzi, Philip Campbell, Karen Campfield, Victoria Campion, Catherine Cargo, Julia Carmona, Dennis Carney, Joshua Casan, Helen Cashman, Lorraine Catt, Michael Cattell, Megan Cavill, Rachel Chadbone, Sridhar Chaganti, Yee Chai, Khai Li Chai, Joshua Chang, Judith Chapman, Oliver G. Chapman, Tamika Chapter, Andrew Charlton, Celina Chau, Saleena Chauhan, Nikesh Chavda, Frederick Chen, Melody Chen, Meng Xi Chen, Melanie Chen, Melissa Chen, Kathleen Cheok, Mai Cheung, Luke Chidgey, Karolina Chmielokliec, Philip Choi, Jae Choi, Anne Chok, Ruchika Chopra, Louise Christopherson, Vicky Chu, Chong Chyn Chua, Pavel Chudakou, Vidushi Chugh, Chi Chung, Erin Clark, Peter Clarke, Kathleen Clarke, Jennifer Clay, Laura Clayton, Mitch Clements, Jonathan Clemmens, Ruth Clifford, Dave Collett, Maia Collins, Emily Collyer, Maureen Connolly, Mark Cook, Sarah Coombs, Jason Coppell, Sophie Cornwell, Claire Corrigan, Elizabeth Coughlin, Jennifer Couling, Tony Cousins, Catriona Cowan, Christine Cox, Catherine Cox, Luke Coyle, Emily Craig, Thomas Creasey, Laura Croan, Jane Croft, Nicola Crosbie, Josephine Crowe, Helen Crowther, Jane Crozier, Naomi Culleton, Jonathan Cullis, Anita Cumming, Michelle Cummins, Adam Cunningham, Cameron Curley, Samantha Curtis, Robert Cuthbert, Kirsty Cuthill, Dinusha A Dahahayake, Amy Dang, Marc Davies, Ceri Davies, Emily Dawson, Tom Day, Kanchana De Abrew, Hugues De Lavallade, Neelaskshi De Silva, Georgina Dean, Christopher Deane, Lisa Demosthenous, Amisha Desai, Michael Desborough, Ian Devanny, Jay Dhanapal, Sundip Dhani, Vicky Di Martino, Emmy Dickens, Carmen DiCorleto, Louise Dinnett, Divya Dirisan, Karen Dixon, Kiri Dixon, Inderjit Doal, J Dobivh, Maria Docanto, Helve Doecke, David Donaldson, Kylee Donaldson, Carrie Donohoe, Ashley Douglas, Stephen Doung, Susan Downer, James D'Rozario, Malcolm Drummond, Mark Drummond, Samantha Drummond, Elizabeth Drysdale, Ross D'Souza, Eugene D'Souza, Alex Dunn, David Dutton, Martin Dyson, Kushani Ediriwicurena, Sharon Edleston, Dawn Edwards, Morgan Edwards, Anita Edwards, Nicole Eise, Steven Ellis, Hayley Ellis, Shareef Elmonley, Rosemarie Enstone, Agnes Eordogh, Sharon Erb, Shannon Evans, Megan Evans, Shannon Evans, Megan Evans, Joanne Ewing, Toby Eyre, Adam Facey, Mina Fammy, Jon Farman, Rachel Farnell, Laura Favero, Keith Fay, Karen Ferguson, Laura Fernon, Robin Filshie, Damian Finnegan, Lisa Fisher, Asia Flanagan, Emma Fleck, Simon Fletcher, Harpreet Flora, Catherine Flower, Ioana Fodor, Heather Foley, Emma Folland, Comfort Folorunso, Molly Forbes, Katrina Fordwor, Polly Foster, Vanessa Fox, Thomas Fox, Olesya Francis, Louise Fryearson, Madonna Fuery, Jiin Fung, Michelle Furtado, Leanne Galloway-Browne, Louise Gamble, Jeanette Gamgee, Arundathi Ganapathy, Hayley Gardner, Clare Gardner, Noha Gasmelsheed, Amy Gately, Lynda Gaynor, Alex Gebreid, Ruth Geffens, Rachel George, Aniko Gertner, Manar Ghebeh, Emanuela Ghirardini, Melainie Giddings, Sandra Gillett, Karen Gillett, Pratyush Giri, Chris Glass, Sarah Glewis, Sarah Gooding, Olivia Gordon, Joanne Gordon, David Gottlieb, Koushik Gowda, Elysie Gower, Nicola Gray, Jo Grayer, Elaine Greaves, Sally Anne Greenaway, Graeme Greenfield, Matthew Greenwood, Gareth Gregory, James Griffin, Julia Griffith, James Griffith, Lindsey Griffiths, Paulina Grzegrzolka, Yisu Gu, Jo Guest, Rosanna Guinai, Veena Gullapalli, A. Gunolr, Lina Guo, Wayne H, Sophia Hagua, Senait Haile, Richard Hall, Maryam Hamdollah-Zadeh, Zahra Hanif, Kathleen Hanlon, Nicholas Hann, Ramez Hanna, Guy Hannah, Sameera Hapuarachchi, Jacinta Hardman, Alison Hardy, Anthony Harris, Kylie Harris, Beth Harrison, Simon Harrison, Lea-Anne Harrison, Sean Harrop, Caroline Harvey, Faye Hatcliffe, Jo Hawking, Matthew Hawkins, Janet Hayden, Michelle Hayman, Elizabeth Haynes, Nicholas Heaney, Andrew Hebbard, Jenny Hempton, Sasanka Hendunneti, Maeve Henry, Jonathan Heywood, Catherine Hildyard, Lydia Hill, Annette Hilldrith, Petar Hitev, Smita Hiwase, Devendra Hiwase, Chris Hoare, Renate Hodge, Amy Holloway, Chloe Holt, Kelly Holton, Lauren Homer, Gillian Horne, Noemi Horvath, Linda Hotong, Kristen Houdyk, Katy Houseman, Ilda Hoxhallari, Hannah Hsu, Nina Hsu, Gillian Huang, Kerryn Hudson, Melanie Hufton, Timothy Hughes, Siobhan Hughes, Kate Hurley, Rosie Huxley, Temitope Ibitoye, Abubaken Ibrouf, Farha Inam, Tishya Indran, Karen Ingham, Calum Innes, David Irvine, Sarah Jaafar, Manish Jain, Laura Jameson, Pardeep Janjua, Rebecca Jarvis, Abirami Jatheendran, Abbie Javed, Sheila Jen, Shailesh Jobanpura, Irene Jobson, Deborah John, Sophie Johns, Amanda Johnston, Hollie Jones, Francesca Jones, Karolina Joniak, Michael Jovanovic, Anita Jovic, Lauren Joyce, Andrew Judd, Sudhakar Kakarlamudi, Nick Kakaroubas, Maggie Kalita, Shirly Kam, Julie Kan, P Kandle, Alex Kanellopoulos, Chien Kao, Maria Kaparou, Charamlampos Kartsios, Vicki Katsioulas, Russell Kaye, Katie Keen, Richard Kelly, Pauline Kelly, Donna Kelly, Melanie Kelly, Glen Kennedy, Nola Kennedy, Angela Kenny, Zoe Kenworthy, Ian Kerridge, Murali Kesavan, Angelika Khafizi, Muhammad Khakwani, Amna Khalid, Kate Khamly, Anjum Khan, Dalia Khan, Mojid Khan, Lubna Khan, Mona Khoo, Asim Khwaja, Grace Kim, Andrew King, Vicky King, Donna King, Francesca Kinsella, David Kipp, Pachoo Kirandeep, Laura C. Kirui, Bhuvan Kishore, Christopher Knectlhi, Amy Knot, Armit Knot, Cathy Ko, Caitlin Kolaric, Ray Koo, Mary Kotadia, Jaimal Kothari, Panagiotis D. Kottaridis, Gajan Kuiluinathan, Austin Kulasekararaj, John Kwan, Marwan Kwok, Phillip Kwok, Fiona Kwok, Kristiina Laane, Deena Lad, Jennifer Laird, Ada Lam, Mary Lane, Monica Lanenco, Susan Lang, Alex Langridge, Catherine Langton, Michelle Lannon, Annie Latif, Maya Latimer, Ruth Latter, I-Jun Lau, Sarah Lawless, Theresa Lawless, Mike Leach, Sarah Leaney, Heather Leary, James Leavy, Abbey LeBlanc, Vivienne Lee, Edwin Lee, Jenny Lee, Tamara Lee, Marian Leischkie, Emma Leitinger, Christopher Leon, Jayne Leonard, David Lewis, Ian Lewis, Tania Lewis, Daniel Lim, Kelly Littlewood, Dara Liu, Joanna Loh, Anand Lokare, Anand Lokare, Oliver Lomas, Richard Lovell, Theresa Lowe, Lisa Lowry, Marcin Lubowiecki, Rebecca Lumb, Gail Lynch, Amanda Macaulay, Lyndsey MacDonald, Jill MacDonald-Burn, Margaret Macmillan, Karen Maddock, Tomas Mahaliyana, Cassandra Mahon, Alison Maidment, Susie Maier, Michelle Mairos, Mahseeman Majid, Ka L Mak, Anne Mak, Arunthrthy Malendrayogau, Hana Malham, Felicity Malyon, Vineela Mandadapu, Laura Mandel, Sarah Mant, Ruth Manton, Nadjoua Maouche, Muhammad G. Maqbool, Gregory Marchant, Mariana Marinho, David Marks, Mike Marner, Helen Marr, Gillian Marshall, Siobhan Martin, Abigail Martin, Maria Marzolini, Kiara Mason, Jonathan Massie, Rebecca Masson, Vidya Mathavan, Siju Mathew, Judith Mathie, Lehenta Mattocks, Bernard Maybury, Georgina Mayer, Chyrelle McAlister, Jo McAllister, Stewart McConnell, James McCracken, Liz McCullagh, Rory McCulloch, Christopher Mcdermott, Kerian Mcdonald, Laura McGinniss, Fiona McGurk, Jessica McIlwain, Kirsten McIver, Pam Mckay, Lorraine McKenna, Donal Mclornan, Coalon McMahon, Linda McNeice, Susan McNeill, Molly McNickle, Fiona McQueen, Simon McRae, Bobby McTaggart, Jenny Mehew, Varnn Mehra, Michelle Melly, Tara Menichelli, Ken Micklethwatte, Loredana Mihailescue, Aleksander Mijovic, Hannah Millband, Lucy Miller, Samuel T. Millien, James Milnthorpe, Adrian Minson, Eva Molnar, Marc Monsour, Mary Moody, Rebecca Moon, Sally Moore, Katy Moore, Kelly Morgan, Rebecca Morralley, Denise Morris, Kirk Morris, Nicole Morrison, Merinda Moss, Muhammad Mughal, Paul Muir, David Mukkath, Aasiyu Mulla, Stephen Mulligan, Joanne Mullings, Angela Mulqueen, Caitlin Muluey, Sarah Murdoch, Sura Murrani, Vidhya Murthy, Jimmy Musngi, Nadreen Mustafa, Tracey Mynes, Anastasios Nalpantidis, Harshal Nandurkar, Linda Nardone, Latifa Nasari, Latifa Nasari, Monica Nash, Georgina Naylor, Loretta Ngu, Melissa Nguethina, John Nguyen, Joseph Nguyen, Wendy Nichol, Emma Nicholls, Catherine S. Nicole, Phillip Nicolson, David Nielson, Emmanouil Nikolousis, Georgina Nix, Rita Njoku, Jane Norman, Amy Norman, Phoebe Norris, Daniel North, Megan Norwood, Gaynor Notcheva, Igor Novitzky-Basso, Joseph Nyaboko, Maria Nygren, Ingrid Obu, Siobhan O'Connell, Jody O'Connor, Deanna O'Kelly, Aideen O'Niell, Jeremy Ony, Kathy Oo, April Oo, Anne Oppermann, Anne Oppermann, Ruth Orr, Mary O'Sullivan, Jennifer Page, Emma Palfreyman, Shankaranarayana Paneesha, Shyam Panicker, Catherine Parbutt, Elesha Parigi, Gemma Paris, Tracey Parker, Caroline Parnell, Christopher Parrish, Alex Parsons, Mioara Pasat, Natasha Patel, Vijay Patel, Pooja Patel, Chaya Patel, Nalini Pati, Andrea Patterson, Lauren Paul, Danielle Payet, Elspeth Payne, Victoria Peachey, Amanda Pearson, Andy Peniket, Laura Percy, Millicent Pereyra, Omer Pervaiz, Gunjan D Phalod, Anh Pham, Jason Pho, Keir Pickard, Michael Pidcock, Anna Piggin, Anna Piggin, Yalda Pishyar, Abigail Pocock, Ranjendres Pol, Paolo Polzella, Sonia Poolan, Vicki Portingale, Claire Posnett, Sandeep Potluri, Victoria Potter, Guy Pratt, Catherine Prodger, Andres Pueblo, Anish Puliyayil, Pratheepan Puvanakumar, Abdul Qadri, Hang Quach, Michael Quinn, Mark Rafferty, Marzia Rahman, Kavita Raj, Sonia Raj, Ramina Rajendran, Radha Ramanan, Karthik Ramasamy, Alexandros Rampotas, Natasha Ranchhod, Sabia Rashid, Sunita Ratanjee, Gurpreet Rathore, Sumita Ratnasingam, Manjit Rayat, Michael Rayner, Rebecca Reddell-Denton, Nicola Redding, Udaya Reddy, Atique Rehman, Carol Rice, Iwona Riches, Thomas Rider, John Riley, Ciro Rinaldi, Kayleigh Roberts, Andrew Roberts, Bryony Robertson, Peter Robertson, Dan Robinson, Rebecca Robinson, Emma Robjohns, Laura Robledo, Ana Rodrigues, Chris Rofe, Bridie Roff, Rachel Rogers, Jill Rolt, Carmela Rooney, Kathy Rose, Hannah Rose, David Ross, Shahara Rouf, Claire Rourke, David Routledge, Janet Ruggiero, Simon Rule, Richard Rumsey, Cherry Sagge, Helen Saldhana, Richard Salisbury, Sarah Salisbury, Ross Salvaris, Kay Sanders, Mirriam Sangombe, Anna Sanigorska, Kristine Santos, Taylah Sarkis, Anita Sarma, Natalie Saunders, Kara Schmidt, Anja Schmidtmann, Ann Schumacher, Tom Scorer Scorer, Asleigh Scott, Ingrid Seath, Frances Sejman, Adrian Selim, Nadia Shamim, Jocelyn Shan, Naranie Shanmuganathan, Shaminie Shanmugaranjan, Michelle Sharpe, Faye Sharpley, Emma Shaw, Cara Sheath, Oonagh Sheehy, Vivian Shen, Solomon Sherbide, Mathew Sheridan, Jane Sheridan, Matthew Sheridon, Tracy Shields, Hau V Sim, Shirlene Sim, Matt Sims, Lydia Singaraveloo, Gurcharan Singh, Jasmine Singh, Shree Sladesal, Andrew Sloan, Peter Slobodian, Sophie Smith, Sarit Smith, Claire Smith, Alastair Smith, Neil Smith, Katherine Snowden, Joel Solis, Denise Somios, Jade Soo, Michelle Spanevello, Madeleie Spaulding, Laura Spence, Liz Spillane, Alisha Spiteri, Naomi Sprigg, Sally Springett, Lynn Stafford, Katherine Stainthorp, Kate Stark, Louise Steeden, Ella Stephen, Aisling Stephenson, Andrew Stewart, Orla Stewart, Emma Stobie, Chelsea Stokes, Jacqui Streater, Charlie-Marie Suddens, Surenthini Suntharalingam, Narinder Surana, Robyn Sutherland, Antony Sutherland, David Sutton, Connor Sweeney, Reilly Sweet, Aniko P Szucs, Leila E. Taheri, Hinesh Tailor, Constantine Tam, Constantine Tam, George Tambakis, Mary Tamplin, Chee Tan, Sui Tan, Joanne Tan, Zhi Tan, Tatiana Taran, Fiona Tarpey, Angela Taseka, Suzy Tasker, Maciej Tatarczuch, Sarrah Tayabali, Hannah Taylor, Robert Taylor, Melaine Taylor, Ella Taylor-Moore, Lesley Teasdale, Elizabeth Tebbet, Aditya Tedjasepstra, Aditya Tedjaseputra, Oummy Tepkumkun, Andrew Terpstra, Wayne Thomas, Shanice Thomas, Rachel Thompson, Thomas Thornton, Bronwyn Thorp, Moi Yap Thrift, Phillipa Thwaites, Jasmine Timbres, Lauren Tindall, Ing Soo Tiong, Nicole Tippler, Tony Todd, Shirley Todd, Neil Toghill, Eve Tomlinson, Jacinta Tooth, M. Topp, Nicola Trail, Nguyen Tran, Elizabeth Tran, Vi Tran, Bona Treder, Michelle Tribbeck, Siobhan Trochowski, Maria Truslove, Tsun Tse, Bing Tseu, David Tucker, Kelly Turner, Dianne Turner, Kelly Turner, Herleen Turner, Gillian Turner, Julie Twohig, Thomas Tylee, Micheleine Uhe, Lauren Underhill, Joanne V, Georgina Van der Vliet, Tina Van Tonder, Carrie VanderWeyden, Jerry Varghese, Lachlan Vaughan, David Veale, Nicky Vickaryyous, Kathryn Vince, Jacoba Von Welligh, Sona Vora, Sona Vora, Karan Wadehra, Rebecca Walker, Stephen Walker, Roslyn Wallace, Stephanie Wallniosve, S. Wallwork, Zoe Walmsley, Fiona Walters, Joyce Wang, Angela Wang, Chen Wang, Mercy Wanyika, Dana Warcel, Katrina Wardrobe, Kristian Warnes, Christopher Waterhouse, Adam Waterworth, Caroline Watson, Edmund Watson, Emily Watts, Emma Weaver, Nicholas Weber, Kaytie Webley, Anna Welford, Matt Wells, Sarah Westbury, Jackie Westcott, Robyn Western, Julia Weston, Jessica White, Phillipa White, Anna Whitehead, James Whitehouse, Samantha Wieringa, John Willan, Sandra Williams, Bethany Williams, Stephanie Williamson, Brett Willoughby, Gail Wilmot, Rosalind Wilmott, Joanna Wilson, Emma Wilson, Suzy Wilson, Heather Wilson, Caroline Wilson, Tanya Wilson, Margaret Wilton, Paula Wiltshire, Joanne Wincup, Julia Wolf, Henna Wong, Cyndi Wong, Daniel Wong, Jonathan Wong, Shi Qin Wong, Sarah Wood, Henry Wood, Jackie Wooding, Kelly Woolley, Myles Wright, Myles Wright, Roland Wynn-Williams, Costas Yannakou, Zhi Han Yeoh, Zhi Han Yeoh, David Yeung, Agnes Young, Flora Yuen, Agnes Yuen, Oliver Zaja, Xiao-Yin Zhang, Mei Zhang","doi":"10.1016/s2352-3026(24)00317-x","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00317-x","url":null,"abstract":"Bleeding is common in patients with haematological malignancies undergoing intensive therapy. We aimed to assess the effect of tranexamic acid on preventing bleeding and the need for platelet transfusions.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790066","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":"Triplet therapy for advanced BCR::ABL1 positive myeloid leukaemias.","authors":"Mhairi Copland","doi":"10.1016/s2352-3026(24)00282-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00282-5","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275330","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":"Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial.","authors":"Nicholas J Short,Daniel Nguyen,Elias Jabbour,Jayastu Senapati,Zhihong Zeng,Ghayas C Issa,Hussein Abbas,Cedric Nasnas,Wei Qiao,Xuelin Huang,Gautam Borthakur,Kelly Chien,Fadi G Haddad,Naveen Pemmaraju,Omer S Karrar,Danielle Nguyen,Marina Konopleva,Hagop Kantarjian,Farhad Ravandi","doi":"10.1016/s2352-3026(24)00250-3","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00250-3","url":null,"abstract":"BACKGROUNDAdvanced phase Philadelphia chromosome-positive myeloid disease-consisting of chronic myeloid leukaemia in the myeloid blast phase and in the accelerated phase, and Philadelphia chromosome-positive acute myeloid leukaemia-is associated with poor outcomes. Although previous studies have suggested the benefit of chemotherapy and BCR::ABL1 tyrosine kinase inhibitor combinations, the optimal regimen is uncertain and prospective studies for this rare group of diseases are scant. Preclinical and retrospective clinical data suggest possible synergy between the BCL-2 inhibitor venetoclax and BCR::ABL1 tyrosine kinase inhibitors. We therefore aimed to design a study to evaluate the safety and activity of a novel combination of decitabine, venetoclax, and the third-generation BCR::ABL1 tyrosine kinase inhibitor ponatinib in advanced phase Philadelphia chromosome-positive myeloid diseases.METHODSFor this phase 2 study, patients aged 18 years or older with previously untreated or relapsed or refractory myeloid chronic myeloid leukaemia-blast phase, chronic myeloid leukaemia-accelerated phase, or advanced phase Philadelphia chromosome-positive acute myeloid leukaemia, and an Eastern Cooperative Oncology Group performance status of 0-3 were eligible. Patients were eligible regardless of the number of previous lines of therapy received or previous receipt of ponatinib. Cycle 1 (induction) consisted of a 7-day lead-in of ponatinib 45 mg orally daily (days 1-7), followed by combination therapy with decitabine 20 mg/m2 intravenously on days 8-12, venetoclax orally daily with ramp-up to a maximum dose of 400 mg on days 8-28, and ponatinib 45 mg orally daily on days 8-28. Cycles 2-24 consisted of decitabine 20 mg/m2 intravenously on days 1-5, venetoclax orally 400 mg on days 1-21, and ponatinib orally daily on days 1-28. Response-based dosing of ponatinib was implemented in consolidation cycles, with reduction to 30 mg daily in patients who reached complete remission or complete remission with an incomplete haematological recovery and a reduction to 15 mg daily in patients with undetectable BCR::ABL1 transcripts. The primary endpoint was the composite rate of complete remission or complete remission with incomplete haematological recovery in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT04188405) and is still ongoing.RESULTSBetween July 12, 2020, and July 8, 2023, 20 patients were treated (14 with chronic myeloid leukaemia-blast phase, four with chronic myeloid leukaemia-accelerated phase, and two with advanced phase Philadelphia chromosome-positive acute myeloid leukaemia). The median age was 43 years (IQR 32-58); 13 (65%) patients were male and seven (35%) were female; and 12 (60%) were White, three (15%) were Hispanic, four (20%) were Black, and one (5%) was Asian. 12 (60%) patients had received 2 or more previous BCR::ABL1 tyrosine kinase inhibitors, an","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275331","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 fedratinib in patients with myelofibrosis previously treated with ruxolitinib (FREEDOM2): results from a multicentre, open-label, randomised, controlled, phase 3 trial.","authors":"Claire N Harrison,Ruben Mesa,Moshe Talpaz,Haifa Kathrin Al-Ali,Blanca Xicoy,Francesco Passamonti,Francesca Palandri,Giulia Benevolo,Alessandro Maria Vannucchi,Clemence Mediavilla,Alessandra Iurlo,InHo Kim,Shelonitda Rose,Patrick Brown,Christopher Hernandez,Jia Wang,Jean-Jacques Kiladjian","doi":"10.1016/s2352-3026(24)00212-6","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00212-6","url":null,"abstract":"BACKGROUNDMost patients with myelofibrosis develop ruxolitinib intolerance or disease that is relapsed or refractory, and survival rates after ruxolitinib discontinuation are poor. We aimed to evaluate the safety and efficacy of fedratinib versus best available therapy (BAT) in patients with myelofibrosis previously treated with ruxolitinib.METHODSFREEDOM2 was a multicentre, open-label, randomised, controlled, phase 3 trial in 86 clinics in 16 countries, in which patients aged at least 18 years with intermediate-2 or high-risk myelofibrosis that was relapsed or refractory or intolerant to ruxolitinib with Eastern Cooperative Oncology Group performance status 0-2 were stratified by spleen size by palpation, platelet count, and previous ruxolitinib treatment, and randomly assigned 2:1 by interactive response technology to receive fedratinib 400 mg per day (4 × 100 mg capsules orally once daily, open-label) or BAT. Patients received prophylactic antiemetics and thiamine supplementation, and symptomatic antidiarrhoeals as required. Primary endpoint was proportion of patients reaching spleen volume reduction (SVR) of at least 35% (SVR35) at end of cycle 6 in the intention-to-treat population. This manuscript reports the primary analysis of the trial; follow-up is ongoing. This trial is registered at clinicaltrials.gov, NCT03952039.FINDINGSBetween Sept 9, 2019 and June 24, 2022, of 316 patients screened, 201 were randomly assigned and treated (134 to fedratinib, 67 to BAT [including 52 receiving ruxolitinib]); 46 patients from the BAT group crossed over to fedratinib. Approximately half of enrolled patients were male (fedratinib 75 [56%] of 134; BAT 30 [45%] of 67) and most were White (fedratinib 106 [79%] of 134; BAT 58 [87%] of 67). At data cutoff (Dec 27, 2022), median survival follow-up was 64·5 weeks (IQR 37·9-104·9). SVR35 at end of cycle 6 was seen in 48 (36%) of 134 patients receiving fedratinib versus four (6%) of 67 patients receiving BAT (30% difference; 95% CI 20-39; one-sided p-value <0·0001). During the first six cycles 53 (40%) of 134 patients in the fedratinib group and 8 (12%) of 67 patients in the BAT group had grade 3 or greater treatment-related adverse events, most frequently anaemia (fedratinib 12 [9%] of 134; BAT 6 [9%] of 67) and thrombocytopenia (fedratinib 16 [12%] of 134; BAT 2 [3%] of 67); one patient in the fedratinib group died from acute kidney injury suspected to be related to study drug (no treatment-related deaths in the BAT group). Gastrointestinal adverse events occurred more frequently in the fedratinib group compared with the BAT group, but were mostly grade 1-2 in severity and more frequent in early cycles, and were less frequent than in prior clinical trials. A total of 28 (21%) of 134 patients in the fedratinib group and 3 (4%) of 67 patients in the BAT group had thiamine levels below lower limit of normal per central laboratory assessment, with only one case of low thiamine in the fedratinib arm after the intro","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231512","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}