Blood最新文献_第3页

How I individualize treatment for chronic-phase CML. 我如何个体化治疗慢性粒细胞白血病。

IF 20.3 1区医学

Blood Pub Date : 2025-04-16 DOI: 10.1182/blood.2024026508

Ariel Monet Leyte-Vidal,Neil P Shah

引用次数: 0

International Consensus Statement on Diagnosis, Evaluation, and Research of Richter Transformation: the ERIC Recommendations. 里克氏转化诊断、评估和研究的国际共识声明：ERIC建议。

IF 20.3 1区医学

Blood Pub Date : 2025-04-16 DOI: 10.1182/blood.2024028064

Adam S Kittai,Monia Marchetti,Othman Al-Sawaf,Ohad Benjamini,Alexey V Danilov,Matthew S Davids,Barbara F Eichhorst,Toby A Eyre,Anna Maria Frustaci,Michael J Hallek,Paul Joseph Hampel,Yair Herishanu,Rodney John Hicks,Arnon P Kater,Rebecca L King,José-Ignacio Ignacio Martín-Subero,Carolyn Owen,Erin M Parry,Maurilio Ponzoni,Davide Rossi,Tanya Siddiqi,Stephan Stilgenbauer,Constantine S Tam,Elisa Ten Hacken,Philip A Thompson,William G Wierda,Gianluca Gaidano,Jennifer A Woyach,Paolo Ghia

{"title":"International Consensus Statement on Diagnosis, Evaluation, and Research of Richter Transformation: the ERIC Recommendations.","authors":"Adam S Kittai,Monia Marchetti,Othman Al-Sawaf,Ohad Benjamini,Alexey V Danilov,Matthew S Davids,Barbara F Eichhorst,Toby A Eyre,Anna Maria Frustaci,Michael J Hallek,Paul Joseph Hampel,Yair Herishanu,Rodney John Hicks,Arnon P Kater,Rebecca L King,José-Ignacio Ignacio Martín-Subero,Carolyn Owen,Erin M Parry,Maurilio Ponzoni,Davide Rossi,Tanya Siddiqi,Stephan Stilgenbauer,Constantine S Tam,Elisa Ten Hacken,Philip A Thompson,William G Wierda,Gianluca Gaidano,Jennifer A Woyach,Paolo Ghia","doi":"10.1182/blood.2024028064","DOIUrl":"https://doi.org/10.1182/blood.2024028064","url":null,"abstract":"Richter transformation (RT) is defined as an aggressive lymphoma emerging in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Despite novel therapeutics developed in CLL, RT is associated with poor outcomes. In light of recent progress regarding the diagnostic procedures and therapeutic concepts of RT, an international group of experts, under the coordination of the European Research Initiative on CLL (ERIC), has developed consensus recommendations for clinical procedures and future research on this disease. Patients with RT typically present with a rapid clinical decline, worsening B-symptoms, elevated LDH, and/or rapidly enlarging lymphadenopathy. Workup should include a PET-CT for patients with suspected RT. An excisional biopsy should be taken from an accessible lesion, preferably with the highest FDG avidity, and analyzed for the presence of aggressive lymphoma. The molecular relationship to the original CLL clone(s) should be defined. As no effective standard treatment for RT exists, patients should be treated in a clinical trial. Response of both RT and CLL should be assessed at an early time point, and survival endpoints should be prioritized in trial design. We hope that these recommendations can help to harmonize clinical and translational research and improve outcomes for patients with RT.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"7 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846363","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}

引用次数: 0

The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy. ENHANCE-3研究：venetoclax和阿扎胞苷联合麦格罗单抗或安慰剂治疗不适合强化治疗的未治疗AML。

IF 20.3 1区医学

Blood Pub Date : 2025-04-15 DOI: 10.1182/blood.2024027506

Naval G Daver,Paresh Vyas,Gerwin A Huls,Hartmut Döhner,Sebastien Maury,Jan Novak,Cristina Papayannidis,Carmen Martinez Chamorro,Pau Montesinos,Rabin Niroula,Pierre Fenaux,Jordi Esteve,Shang-Ju Wu,Adrien De Voeght,Jiri Mayer,Peter J M Valk,Lisa Johnson,Mei Dong,Ke Liu,Sowmya Banda Kuwahara,Kenneth Caldwell,Guru Subramanian Guru Murthy

{"title":"The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy.","authors":"Naval G Daver,Paresh Vyas,Gerwin A Huls,Hartmut Döhner,Sebastien Maury,Jan Novak,Cristina Papayannidis,Carmen Martinez Chamorro,Pau Montesinos,Rabin Niroula,Pierre Fenaux,Jordi Esteve,Shang-Ju Wu,Adrien De Voeght,Jiri Mayer,Peter J M Valk,Lisa Johnson,Mei Dong,Ke Liu,Sowmya Banda Kuwahara,Kenneth Caldwell,Guru Subramanian Guru Murthy","doi":"10.1182/blood.2024027506","DOIUrl":"https://doi.org/10.1182/blood.2024027506","url":null,"abstract":"Patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC) have limited treatment options. The phase 3 ENHANCE-3 study aimed to determine whether magrolimab (magrolimab arm) was superior to placebo (control arm) when either was combined with venetoclax and azacitidine. Adults with previously untreated AML who were ineligible for IC were randomized to receive magrolimab (1 mg/kg on days 1 and 4, 15 mg/kg on day 8, 30 mg/kg on days 11 and 15, then weekly for 5 weeks, then every 2 weeks) or placebo, venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter), and azacitidine (75 mg/m2 days 1-7) in 28-day cycles. The primary endpoint was overall survival (OS); key secondary endpoints included complete remission (CR) rate and safety. After randomization of 378 patients, the trial was stopped at a prespecified interim analysis due to futility. At final analysis, with median follow-up of 7.6 months (magrolimab arm) vs 7.4 months (control arm), median OS was 10.7 vs 14.1 months (HR, 1.178 [95% CI, 0.848-1.637]). The CR rate within 6 cycles was 41.3% vs 46.0%. Addition of magrolimab to venetoclax and azacitidine resulted in more fatal adverse events (19.0% vs 11.4%), primarily driven by grade 5 infections (11.1% vs 6.5%) and respiratory events (2.6% vs 0%). There were similar incidences of any-grade infections, febrile neutropenia, and neutropenia between arms. These results highlight the difficulty in improving outcomes for patients with AML ineligible for IC. This trial was registered at www.clinicaltrials.gov as #NCT05079230.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"17 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841202","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}

引用次数: 0

Breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria throughout clinical trials: from definition to clinical practice. 突破溶血在阵发性夜间血红蛋白尿贯穿临床试验：从定义到临床实践。

IF 20.3 1区医学

Blood Pub Date : 2025-04-15 DOI: 10.1182/blood.2024027574

Bruno Fattizzo,Francesco Versino,Wilma Barcellini

{"title":"Breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria throughout clinical trials: from definition to clinical practice.","authors":"Bruno Fattizzo,Francesco Versino,Wilma Barcellini","doi":"10.1182/blood.2024027574","DOIUrl":"https://doi.org/10.1182/blood.2024027574","url":null,"abstract":"Breakthrough hemolysis (BTH) is the hemolytic exacerbation occurring in a patient with paroxysmal nocturnal hemoglobinuria (PNH) on treatment with anti-complement therapies. In this review article we analysed the definition, frequency and severity of BTH events across phase 3 clinical trials with terminal (anti-C5 ravulizumab and crovalimab) and complement inhibitors upstream C5 (anti-C3 pegcetacoplan, alternative-pathway inhibitors iptacopan and danicopan), as well as from real-world reports. Furthermore, we reviewed the impact of the various compounds on quality of life and patients reported outcomes. In particular, BTH may occur with all complement inhibitors, with a frequency of 10-15% over 6 months with eculizumab, crovalimab, and pegcetacoplan, and <5% with ravulizumab, iptacopan, and danicopan plus anti-C5. By prolonging the follow-up, the frequency of BTH appeared increased in pegcetacoplan treated patients (nearly 24% at 1 year) as compared to both anti-C5, iptacopan, and double inhibition with danicopan plus anti-C5. BTH risk appears associated with patients' features, particularly suboptimal response/failure of previous complement inhibitor. Transfusions were required in about half of cases and modifications of anti-complement therapy included anticipation of the next anti-C5 dose and addition of eculizumab in patients on proximal inhibitors. Breakthrough thromboses were rare, though anti-coagulant prophylaxis should be considered during severe episodes. Complement amplifying conditions were observed in about half of cases and were more frequently infections. Treatment adherence, optimization of the administration schedule, anticoagulant prophylaxis, as well as education of patients and physicians remain important factors to prevent BTH and its complications.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"26 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841255","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}

引用次数: 0

Maternal Tmprss6 is required for hepcidin suppression and fetal health. 母体Tmprss6是抑制hepcidin和胎儿健康所必需的。

IF 20.3 1区医学

Blood Pub Date : 2025-04-15 DOI: 10.1182/blood.2024027563

Katherine Louise Fielding,Cavan Bennett,Anne Pettikiriarachchi,Naomi Jones,Rebecca Harding,Alistair R D McLean,Louise M Randall,Ute Schaeper,Alberto Martinez,Ricardo Ataide,Sant-Rayn Pasricha

引用次数: 0

Outcomes of PLAT-02 and PLAT-03: Evaluating CD19 CAR T-Cell Therapy and CD19-expressing T-APC Support in Pediatric B-ALL. platt -02和platt -03的结果：评估CD19 CAR - t细胞治疗和CD19表达T-APC对儿童B-ALL的支持

IF 20.3 1区医学

Blood Pub Date : 2025-04-15 DOI: 10.1182/blood.2025028359

Colleen Annesley,Kristy D Seidel,Qian Wu,Corinne Summers,Alan S Wayne,Michael A Pulsipher,Anurag K Agrawal,Christopher T Brown,Stephanie Mgebroff,Catherine G Lindgren,Stephanie D Rawlings-Rhea,Wenjun Huang,Ashley Wilson,Michael C Jensen,Julie R Park,Rebecca A Gardner

{"title":"Outcomes of PLAT-02 and PLAT-03: Evaluating CD19 CAR T-Cell Therapy and CD19-expressing T-APC Support in Pediatric B-ALL.","authors":"Colleen Annesley,Kristy D Seidel,Qian Wu,Corinne Summers,Alan S Wayne,Michael A Pulsipher,Anurag K Agrawal,Christopher T Brown,Stephanie Mgebroff,Catherine G Lindgren,Stephanie D Rawlings-Rhea,Wenjun Huang,Ashley Wilson,Michael C Jensen,Julie R Park,Rebecca A Gardner","doi":"10.1182/blood.2025028359","DOIUrl":"https://doi.org/10.1182/blood.2025028359","url":null,"abstract":"This study reports outcomes of PLAT-02, a phase 2 trial of SCRI-CAR19, a second-generation CAR T-cell product with FMC63 scFv and 41BB costimulation, in pediatric and young adult patients with B-cell acute lymphoblastic leukemia; and PLAT-03, a companion study evaluating exogenous CD19 antigen stimulation with serial infusions of T cells expressing truncated CD19, T-cell antigen presenting cells (T-APCs). The efficacy cohort of PLAT-02 (n=72 patients, median age 12.5 years) received fludarabine/cyclophosphamide lymphodepletion followed by a dose of 1X106 CAR+ T cells/kg. MRD-negative complete remission rate was 89%. Leukemia free survival (LFS) with 95% CI at 1 and 2 years was 0.71 (0.58, 0.81) and 0.64 (0.51, 0.75). Patients with low disease burden had significantly higher 1-year LFS (0.91 vs. 0.42). Rapid in vivo contraction of CAR T cells after infusion was associated with CAR loss within six months compared to those without rapid contraction (57% vs. 19%, respectively). Most common grade 3/4 adverse events included cytokine release syndrome in 13% and neurotoxicity in 16%. The companion pilot, PLAT-03, enrolled 26 patients, and 19 received T-APCs. Neither cytokine-release syndrome nor neurotoxicity were observed after T-APC infusion. T-APC infusion in patients improved persistence (P=0.03) with rapid CAR T-cell contraction was associated with decreased early CAR loss (20% with T-APC vs. 57% without). Further exploration of serial artificial CD19 antigen exposure is warranted based on these pilot results. PLAT-02 (NCT02028455) and PLAT-03 (NCT03186118).","PeriodicalId":9102,"journal":{"name":"Blood","volume":"108 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841198","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}

引用次数: 0

The evolving landscape of hereditary stomatocytosis. 遗传性口细胞增多症的演变景观。

IF 20.3 1区医学

Blood Pub Date : 2025-04-15 DOI: 10.1182/blood.2024024294

Immacolata Andolfo,Achille Iolascon,Roberta Russo

{"title":"The evolving landscape of hereditary stomatocytosis.","authors":"Immacolata Andolfo,Achille Iolascon,Roberta Russo","doi":"10.1182/blood.2024024294","DOIUrl":"https://doi.org/10.1182/blood.2024024294","url":null,"abstract":"Hereditary stomatocytosis represents a heterogeneous group of inherited erythrocyte membrane defects characterized by hemolytic anemia of variable degree, with alterations in cellular salt and water, ranging from dehydration to overhydration, and the presence of stomatocytes on peripheral blood smear. This condition encompasses various subtypes, each with distinct clinical and genetic features. The pathophysiology underlying these conditions involves altered red blood cell membrane properties, leading to impaired deformability, alterations in cation permeability and volume, causing increased susceptibility to hemolysis. Advancements in genetic testing have enabled the identification of some causative genes in the last years, such as PIEZO1, KCNN4, and ABCB6. These genetic discoveries have facilitated a deeper understanding of the molecular mechanisms underlying the pathogenesis and have paved the way for improved diagnostic accuracy and genetic counseling. This review provides an overview of the clinical presentation, pathophysiology, molecular genetics, diagnosis, and management strategies of hereditary stomatocytosis, highlighting recent advancements in the field of dehydrated hereditary stomatocytosis, or hereditary xerocytosis, and hepatic iron overload. This latter is directly associated with the physiological role of PIEZO1, the causative gene of DHS, at hepatic and macrophagic levels. Particularly, gain-of-function mutations in PIEZO1 account for a pleiotropic syndrome characterized by different phenotypes depending on the expression of PIEZO1 at multiple cells and tissues.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"3 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841258","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}

引用次数: 0

DNMT3A mutations are unlikely to affect interferon alfa treatment outcomes in patients with polycythemia vera. DNMT3A突变不太可能影响真性红细胞增多症患者的干扰素治疗结果。

IF 20.3 1区医学

Blood Pub Date : 2025-04-15 DOI: 10.1182/blood.2024027528

Ghaith Abu-Zeinah,Katie Erdos,Neville Lee,Yara Ganom,Christoph Klade,Kurt Krejcy,Heinz Gisslinger,Richard T Silver,Joseph Michael Scandura

引用次数: 0

SMAC mimetics in action in chronic myeloid leukemia. SMAC模拟物在慢性髓性白血病中的作用。

IF 20.3 1区医学

Blood Pub Date : 2025-04-10 DOI: 10.1182/blood.2024027994

Ali G Turhan

引用次数: 0

CD3×CD20 bispecifics + chemotherapy: good news for R/R DLBCL. CD3×CD20双特异性+化疗：R/R DLBCL的好消息。