Blood最新文献

{"title":"rADAMTS13 in cTTP: a new standard of care?","authors":"Ahmet Emre Eşkazan","doi":"10.1182/blood.2025029097","DOIUrl":"https://doi.org/10.1182/blood.2025029097","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"30 1","pages":"2243-2244"},"PeriodicalIF":20.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992000","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":"Trafficking on the road to neutropenia.","authors":"Seth J Corey,Andrei I Ivanov","doi":"10.1182/blood.2024026563","DOIUrl":"https://doi.org/10.1182/blood.2024026563","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"53 1","pages":"2237-2239"},"PeriodicalIF":20.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992018","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":"Defective neutrophil clearance in JAK2V617F myeloproliferative neoplasms drives myelofibrosis via immune checkpoint CD24.","authors":"Eman Khatib-Massalha,Christian Andrea Di Buduo,Agathe L Chédeville,Ya-Hsuan Ho,Yexuan Zhu,Elodie Grockowiak,Yuki Date,Lam Tan Khuat,Zijian Fang,Jose Quesada-Salas,Eva Carrillo Félez,Matteo Migliavacca,Isabel Montero,José Antonio Pérez-Simón,Alessandra Balduini,Simón Méndez-Ferrer","doi":"10.1182/blood.2024027455","DOIUrl":"https://doi.org/10.1182/blood.2024027455","url":null,"abstract":"Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell-driven malignancies marked by excessive myelopoiesis and high risk of myelofibrosis, which remains therapeutically challenging. Senescent neutrophils home daily to the bone marrow (BM) to be cleared by macrophages. This avoids their accumulation, which can increase the risk of chronic inflammation or oncogenesis. Neutrophils carrying the most common oncogenic MPN driver (JAK2V617F) are protected from apoptosis, which may prolong their lifespan and enhance their pro-inflammatory activity. On the other hand, abnormal interactions of neutrophils with megakaryocytes (\"emperipolesis\") have been associated with BM fibrosis in disparate hematological disorders, including MPN and grey platelet syndrome; however, the underlying pathophysiology remains unclear. We investigated neutrophil homeostasis and cellular interactions in MPN. We found that senescent neutrophils evade homeostatic clearance and accumulate in JAK2V617F MPN, but not in MPN caused by the second most prevalent mutations affecting Calreticulin (CALR) gene. This is explained by GM-CSF-JAK2-STAT5-dependent upregulation of the \"don't-eat-me\" signal CD24 in neutrophils. Mechanistically, JAK2V617F CD24hi neutrophils evade efferocytosis, invade megakaryocytes and increase active TGF-b. Collectively, JAK2V617F neutrophil-megakaryocyte interactions promote platelet production in a humanized bioreactor and myelofibrosis in mouse models. Notably, chronic antibody blockade or genetic loss of CD24 restores clearance of senescent neutrophils, reduces emperipolesis and active TGF-b. Consequently, CD24 blockade improves thrombocytosis and prevents myelofibrosis in MPN mice. Taken together, these findings reveals defective neutrophil clearance as a cause of pathogenic microenvironmental interactions of inflammatory neutrophils with megakaryocytes, associated with myelofibrosis in MPN. Our study postulate CD24 as a candidate innate immune checkpoint in MPN.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"5 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065831","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":"Sustained bone marrow and imaging MRD negativity for 3 years drives discontinuation of maintenance post-ASCT in myeloma.","authors":"Evangelos Terpos, Panagiotis Malandrakis, Ioannis Ntanasis-Stathopoulos, Ioannis V Kostopoulos, Evangelos Eleutherakis-Papaiakovou, Nikolaos Kanellias, Vasiliki Spiliopoulou, Magdalini Migkou, Despina Fotiou, Foteini Theodorakakou, Efstathios Kastritis, Maria Gavriatopoulou, Ourania E Tsitsilonis, Meletios-Athanasios Dimopoulos","doi":"10.1182/blood.2024027686","DOIUrl":"10.1182/blood.2024027686","url":null,"abstract":"<p><strong>Abstract: </strong>Discontinuation of lenalidomide maintenance after autologous stem cell transplantation is a burning question within the multiple myeloma (MM) community, especially after the inclusion of minimal residual disease (MRD) in the disease response criteria. In this prospective study, we evaluated the conversion to MRD positivity, the treatment-free survival (TFS), and the progression-free survival (PFS) in 52 patients with MM who discontinued lenalidomide maintenance after achieving sustained bone marrow and imaging MRD negativity for 3 years. Patients who developed MRD positivity after lenalidomide discontinuation restarted lenalidomide maintenance at the same dose. The median follow-up from lenalidomide discontinuation was 3 years. Overall, 12 (23%) patients obtained MRD positivity and restarted lenalidomide maintenance. Only 4 (7.6%) patients progressed; 3 had a biochemical progression and 1 had a clinical progression. The overall median PFS was not reached, whereas the 7-year PFS from diagnosis was 90.2%. The 1-, 2-, and 3-year TFS rates were 93.9%, 91.6%, and 75.8%, respectively, whereas the 1-, 2-, and 3-year landmark PFS rates from maintenance discontinuation (study entrance) were 96.0%, 96.0%, and 92.9%, respectively. There were no statistically significant associations among age, sex, Second Revision International Staging System, type of induction therapy, and use of consolidation therapy and the effect outcomes of PFS and TFS. We conclude that maintenance discontinuation after 3 years of sustained marrow and imaging MRD negativity is associated with low rates of MRD conversion and progressive disease. Thus, in the era of modern antimyeloma treatments, a subgroup of patients may remain treatment free while in complete remission without jeopardizing disease response.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2353-2360"},"PeriodicalIF":21.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514610","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":"A phase 2 Trial of CHOP with Anti-CCR4 Antibody Mogamulizumab for older Patients with Adult T-Cell Leukemia/Lymphoma.","authors":"Makoto Yoshimitsu, Ilseung Choi, Shigeru Kusumoto, Mototsugu Shimokawa, Atae Utsunomiya, Youko Suehiro, Tomonori Hidaka, Kisato Nosaka, Hidenori Sasaki, Shinya Rai, Shinobu Tamura, Satsuki Owatari, Ki-Ryang Koh, Daisuke Nakamura, Masahito Tokunaga, Masaaki Sekine, Yuma Sakamoto, Hiroshi Inagaki, Takashi Ishida, Kenji Ishitsuka","doi":"10.1182/blood.2024027902","DOIUrl":"https://doi.org/10.1182/blood.2024027902","url":null,"abstract":"<p><p>No standard of care for elderly patients with aggressive adult T-cell leukemia/lymphoma (ATL) has been established. We evaluated the efficacy of CHOP every 2 weeks with mogamulizumab (Moga) (Moga-CHOP-14) for untreated elderly patients with ATL. In this multicenter phase 2 trial, patients aged ≥66 years and those aged 56-65 years ineligible for transplantation received 6 cycles of Moga-CHOP-14, followed by 2 cycles of Moga monotherapy. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints were the complete response (CR) rate, overall response rate (ORR), overall survival (OS), 1-year event-free survival (EFS), and safety. We also investigated the impact of CCR4 mutation and Moga-associated cutaneous adverse events (cAEs) on PFS and OS. The study protocol was amended to allow the dosing interval to be extended to 21 days at the physician's discretion. Among 48 evaluable patients, the 1-year PFS was 36.2% (90% confidence interval [CI], 24.9-47.6), with a median follow-up of 1.6 years. One-year OS and EFS were 66.0% (95% CI, 50.6-77.6) and 29.9% (95% CI, 17.6-43.2), respectively. CR and ORR were 64.6% (95%CI, 49.5-77.8) and 91.7% (95% CI, 80.0-97.7). No unexpected toxicities were observed. Of the 47 patients who received ≥2 cycles of CHOP, 20 (42.6%) received CHOP-14, among whom 12 (25.5%) completed 6 cycles. CCR4 mutation and Moga-associated cAE were associated with better OS. This study showed that Moga-CHOP significantly improved PFS, though the optimal interval for CHOP remains undetermined. Moga-CHOP is now considered a preferable first-line treatment for these patients. Clinical Trial Identifier: jRCTs041180130.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075845","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":"Efficacy and safety of azacitidine for VEXAS syndrome: a large-scale retrospective study from the FRENVEX group.","authors":"Vincent Jachiet,Olivier Kosmider,Maxime Beydon,Jerome Hadjadj,Lin-Pierre Zhao,Vincent Grobost,Valentin Lacombe,Guillaume Le Guenno,Yann Nguyen,Jean Benoit Arlet,Jeremie Dion,Mael Heiblig,Alice Garnier,Maxime Samson,Achille Aouba,Sylvain Thepot,Sophie Dimicoli-Salazar,Fabien Dutasta,Benoit Faucher,Estibaliz Lazaro,Veronique Morel,Antoine Neel,Roderau Outh,Holy Bezanahary,Julien Rossignol,Anne-Sophie Alary,Audrey Bidet,Pauline Blateau,Anne Bouvier,Guilaine Boursier,Matthieu Decamp,Benjamin Lebecque,Yannick Le Bris,Pierre Sujobert,Alice Marceau-Renaut,Cedric Pastoret,David Rizzo,Nathalie Boiret-Dupré,Lara Boucher,Stéphanie Dulucq,Franck Genevieve,Cassandra Jadeau,Pierre Lemaire,Romain Vazquez,Jean Baptiste Rieu,Olivier Fain,Sophie Anne Georgin-Lavialle,Lucie Rigolot,Lise Larcher,Pierre Hirsch,Benjamin Terrier,Pierre Fenaux,Arsène M Mékinian,Thibault Comont","doi":"10.1182/blood.2024028133","DOIUrl":"https://doi.org/10.1182/blood.2024028133","url":null,"abstract":"VEXAS (Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic) syndrome is a severe monogenic disorder caused by somatic UBA1 mutations, characterized by inflammation, cytopenias and frequent association with myelodysplastic neoplasms (MDS). Steroid dependence is common, and targeted therapies have demonstrated limited efficacy. Azacitidine (AZA), a hypomethylating agent used in MDS, has shown potential in VEXAS but data remain limited. This multicenter retrospective study assessed AZA efficacy and safety in 88 genetically confirmed VEXAS patients from the FRENVEX (French VEXAS) group, 80% meeting WHO 2022 MDS criteria. Inflammatory response rates were 41% at 6 months and 54% at 12 months, regardless of MDS status. A total of 50 (61%) patients achieved inflammatory response, with 70% occurring at 6 months, suggesting a delayed median response. Among responders, relapse-free survival on AZA was 90% at 1 year and 85% at 5 years. Of the 12 responders who discontinued AZA, 9 relapsed after a median of 3.1 years (range: 0.4-5.6), with effective re-exposure in 4 of 5 patients. Hematological responses included red blood cell transfusion independence in 65% and platelet improvement in 77% of patients. Molecular response, defined as a ≥25% reduction in UBA1 variant allele frequency (VAF), was observed in 65% of patients, all of whom achieved inflammatory and hematological responses; and VAF dropped below 2% in 43% of cases. Infections (34%) and cytopenias (36%) were common, particularly during the first three cycles. This study establishes AZA as an effective therapy for VEXAS, improving inflammation, cytopenias, and UBA1 clonal burden, warranting larger prospective trials.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"3 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065834","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":"FLT3 is genetically essential for ITD-mutated leukemic stem cells but dispensable for human hematopoietic stem cells.","authors":"Joana L Araújo, Elvin Wagenblast, Veronique Voisin, Jessica McLeod, Olga I Gan, Suraj Bansal, Liqing Jin, Amanda Mitchell, Blaise Gratton, Sarah Cutting, Andrea Arruda, Monica Doedens, Anthea Travas, Dennis Kim, Jose-Mario Capo-Chichi, Sagi Abelson, Mark D Minden, Jean C Y Wang, Manuel A Sobrinho-Simões, Perpétua Pinto-do-Ó, Eric Lechman, John E Dick","doi":"10.1182/blood.2024025886","DOIUrl":"10.1182/blood.2024025886","url":null,"abstract":"<p><strong>Abstract: </strong>Leukemic stem cells (LSCs) fuel acute myeloid leukemia (AML) growth and relapse, but therapies tailored toward eradicating LSCs without harming normal hematopoietic stem cells (HSCs) are lacking. FMS-like tyrosine kinase 3 (FLT3) is considered an important therapeutic target due to frequent mutation in AML and association with relapse. However, there has been limited clinical success with FLT3 drug targeting, suggesting either that FLT3 is not a vulnerability in LSC or that more potent inhibition is required, a scenario where HSC toxicity could become limiting. We tested these possibilities by ablating FLT3 using CRISPR/Cas9-mediated FLT3 knockout (FLT3-KO) in human LSCs and HSCs followed by functional xenograft assays. FLT3-KO in LSCs from FLT3-internal tandem duplication (ITD)-mutated but not FLT3-wild-type AMLs resulted in short-term leukemic grafts of FLT3-KO edited cells that disappeared by 12 weeks. By contrast, FLT3-KO in HSCs from the fetal liver, cord blood, and adult bone marrow did not impair multilineage hematopoiesis in primary and secondary xenografts. Our study establishes FLT3 as an ideal therapeutic target where ITD-positive LSCs are eradicated upon FLT3 deletion whereas HSCs are spared. These findings support the development of more potent FLT3-targeting drugs or gene-editing approaches for LSC eradication to improve clinical outcomes.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2361-2373"},"PeriodicalIF":21.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999746","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":"Therapeutic switch from plasma to recombinant ADAMTS13 for patients with congenital TTP from Japanese real-world data.","authors":"Kazuya Sakai, Atsushi Hamamura, Yoshiko Yoshimura, Miyuki Abe, Yoshiyuki Ogawa, Kazuki Tanaka, Norimichi Hattori, Tazuko Tokugawa, Rie Kanai, Fumiyoshi Ikejiri, Masahiro Takeyama, Teruhisa Taoka, Naoki Fujita, Minoru Kanaya, Katsuyoshi Koh, Hiroshi Shiragami, Hidekazu Azumi, Kenki Saito, Masanori Matsumoto","doi":"10.1182/blood.2024027516","DOIUrl":"10.1182/blood.2024027516","url":null,"abstract":"<p><strong>Abstract: </strong>Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultrarare disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and ischemic organ damage caused by pathogenic ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) variants. ADAMTS13-containing product, including fresh-frozen plasma (FFP), and plasma-derived factor VIII concentrates are commonly used to supply ADAMTS13; however, frequent hospital visits and allergic reactions are major drawbacks. A recombinant ADAMTS13 (rADAMTS13) was recently developed to address these issues. However, real-world evidence has not been reported owing to the rarity of this condition. This study compared the efficacy and safety of FFP and rADAMTS13 in 14 Japanese patients, including 5 patients with end-stage renal disease who were excluded from the phase 3 trial. The median peak level of ADAMTS13 activity 15 minutes after rADAMTS13 administration was significantly higher than that after FFP (68.4% vs 15.9%; P < .001). ADAMTS13 activity 1 week after rADAMTS13 administration was well maintained compared with FFP infusion (11.6% vs 5.1%; P < .001). Patients reported no allergic reactions after rADAMTS13 administration and appreciated the convenience of a single infusion of rADAMTS13, suggesting that rADAMTS13 is a safe and effective alternative to FFP in patients with cTTP. To our knowledge, this is the first publication of patients with cTTP who switched FFP to novel rADAMTS13 from Japanese real-world data.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2390-2395"},"PeriodicalIF":21.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639671","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":"Right time: stopping multiple myeloma maintenance.","authors":"Philip McCarthy,Hemn Mohammadpour","doi":"10.1182/blood.2025028814","DOIUrl":"https://doi.org/10.1182/blood.2025028814","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"30 1","pages":"2241-2242"},"PeriodicalIF":20.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991972","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":"Introduction to a How I Treat series on transfusion medicine.","authors":"Erica M Wood","doi":"10.1182/blood.2025028947","DOIUrl":"https://doi.org/10.1182/blood.2025028947","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"5 1","pages":"2233-2234"},"PeriodicalIF":20.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991973","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}