Blood最新文献

{"title":"Impact of immunochemotherapy regimens on outcomes of patients with primary mediastinal B-cell lymphoma in the IELSG37 trial.","authors":"Emanuele Zucca,Luca Ceriani,Giovannino Ciccone,Alice Di Rocco,Maria Cristina Pirosa,Iryna Kriachok,Barbara Botto,Monica Balzarotti,Alessandra Tucci,Sara Veronica Usai,Vittorio Ruggero Zilioli,Elsa Pennese,Luca Arcaini,Anna P Dabrowska-Iwanicka,Andrés J M Ferreri,Francesco Merli,Wei-Li Zhao,Luigi Rigacci,Claudia Cellini,David Hodgson,Codruta Ionescu,Carla Minoia,Elisa Lucchini,Michele Spina,Alexander Fosså,Andrea Janikova,Kate Cwynarski,N George Mikhaeel,Mats Jerkeman,Anastasios Stathis,Kelly S Cozens,Nicoletta Ielmini,Iolanda De Martino,Jan Walewski,Marek Trněný,Franco Cavalli,Umberto Ricardi,Peter W M Johnson,Andrew J Davies,Maurizio Martelli","doi":"10.1182/blood.2025028823","DOIUrl":"https://doi.org/10.1182/blood.2025028823","url":null,"abstract":"The IELSG37 trial enrolled 545 patients with primary mediastinal B-cell lymphoma (PMBCL) and demonstrated that consolidation radiotherapy (RT) can be omitted in patients with complete metabolic response (CMR), defined by the Lugano classification as Deauville score (DS) 1-3. This report evaluates outcomes following different frontline rituximab- and doxorubicin-based immunochemotherapy regimens chosen according to local practice. Patients treated with R-CHOP21 showed a significantly higher percentage of DS 5 than those on other regimens (23.8% vs. 8.2% average, P< 0.001) as well as a trend toward additional unplanned treatments (53.2% vs. 46.9%, P=0.30). The increased risk of poor response was confirmed in a multinomial logistic regression analysis adjusted for age, sex, IPI score, and performance status. R-CHOP21 was also associated with smaller reductions in MTV and less pronounced decreases in SUVmax. Patients with DS 5 more often received additional treatment (RT and/or salvage chemotherapy with or without autologous consolidation) after induction immunochemotherapy (96% vs. 41%, P< 0.001) and experienced significantly poorer outcomes. Although differences in progression-free and overall survival between R-CHOP21 and more aggressive regimens were not statistically significant, R-CHOP21 may increase the risk of additional treatments and may be inadvisable as frontline therapy for PMBCL. NCT01599559.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"53 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043519","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":"Human herpesvirus 6 viremia and encephalitis in CAR T-cell recipients.","authors":"Stephanie Teresa Isaac,David C Bishop,Fahad Shaikh,Kenneth P Micklethwaite,David J Gottlieb,Emily Blyth","doi":"10.1182/blood.2025029057","DOIUrl":"https://doi.org/10.1182/blood.2025029057","url":null,"abstract":"HHV-6 reactivation in CAR T-cell recipients is reported to be rare. Our patient cohort (n=119) experienced a seven-fold higher incidence of viraemia than a previous study and 2 encephalitis cases. Further studies are needed to determine risk factors for infection.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"77 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043520","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":"Targeting STK17B kinase activates ferroptosis and suppresses drug resistance in multiple myeloma.","authors":"Zhibo Yan,Zhannan Han,Yihui Wang,Maja Beus,Yu Zhang,Alfredo Picado,Carrow I Wells,Jian Wu,Loren B Weidenhammer,Karla M Pires,Elizabeth A Leibold,Liang Liu,David M Gooden,Ivan Spasojevic,Erik Soderblom,Yubin Kang,Lawrence H Boise,Timothy M Willson,Mikhail A Nikiforov","doi":"10.1182/blood.2025029950","DOIUrl":"https://doi.org/10.1182/blood.2025029950","url":null,"abstract":"The progression of multiple myeloma (MM), an incurable malignancy of plasma cells, is often associated with the suppression of ferroptosis, a type of cell death driven by iron-dependent lipid peroxidation. The mechanisms underlying this suppression remain largely unknown. Here, we identified STK17B kinase as a critical suppressor of ferroptosis in MM. Elevated levels of STK17B are associated with poor overall survival in MM patients and STK17B expression is significantly higher in relapsed vs newly diagnosed MM cases. We found that inhibiting STK17B in MM cells increased the labile iron pool, enhanced lipid peroxidation, and sensitized cells to conventional anti-MM therapies. Notably, an orally available, in-house-generated STK17B inhibitor induced ferroptosis and significantly reduced tumor growth in MM xenograft mouse models. Mechanistically, proximity labeling assay combined with the phospho-proteomic analysis identified two major regulators of iron uptake and transport as direct targets of STK17B: iron-responsive element binding protein 2 (IREB2) and heat shock protein family B member 1 (HSPB1). We demonstrated that STK17B phosphorylates critical regulatory sites on IREB2 (S157) and HSPB1 (S15), thereby modulating the balance between IREB2 and HSPB1 downstream effectors, pro-ferropototic transferrin receptor and anti-ferroptotic ferritin heavy chain proteins. Furthermore, we demonstrated that STK17B indirectly maintains activating phosphorylation of STAT3, a ferroptosis suppressor and a major driver of MM pathobiology. Our findings uncovered a clinically relevant and targetable STK17B-pIREB2S157/pHSPB1S15 signaling axis that suppresses ferroptosis and contributes to drug resistance in MM.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"37 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068367","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":"Good flatmates: immature neutrophils protect bone integrity.","authors":"Matthias Gunzer","doi":"10.1182/blood.2025030147","DOIUrl":"https://doi.org/10.1182/blood.2025030147","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"22 1","pages":"1259-1260"},"PeriodicalIF":20.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032142","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":"Chavez JC, Dickinson M, Munoz J, et al. Three-year follow-up analysis of first-line axicabtagene ciloleucel for high-risk large B-cell lymphoma: the ZUMA-12 study. Blood. 2025;145(20):2303-2311.","authors":"","doi":"10.1182/blood.2025031033","DOIUrl":"https://doi.org/10.1182/blood.2025031033","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"27 1","pages":"1374"},"PeriodicalIF":20.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032061","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":"Immune dysfunction after cancer remission: scar or disease?","authors":"Michael D Jain,Jonathan Cools-Lartigue","doi":"10.1182/blood.2025029648","DOIUrl":"https://doi.org/10.1182/blood.2025029648","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"9 1","pages":"1255-1257"},"PeriodicalIF":20.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032063","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":"ELEVATE-ing clinical trial reporting in CLL.","authors":"Florian Simon,Othman Al-Sawaf","doi":"10.1182/blood.2025029318","DOIUrl":"https://doi.org/10.1182/blood.2025029318","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"25 1","pages":"1253-1254"},"PeriodicalIF":20.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032062","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":"Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN.","authors":"Jeff P Sharman, Miklos Egyed, Wojciech Jurczak, Alan Skarbnik, Krish Patel, Ian W Flinn, Manali Kamdar, Talha Munir, Renata Walewska, Marie Hughes, Laura Maria Fogliatto, Yair Herishanu, Versha Banerji, George Follows, Patricia Walker, Paolo Ghia, Ann Janssens, John C Byrd, Emmanuelle Ferrant, Alessandra Ferrajoli, William G Wierda, Catherine Wangui Wachira, Batul T Suterwala, Paulo Miranda, Veerendra Munugalavadla, Chuan-Chuan Wun, Jennifer A Woyach","doi":"10.1182/blood.2024024476","DOIUrl":"10.1182/blood.2024024476","url":null,"abstract":"<p><strong>Abstract: </strong>Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia. We present results from ELEVATE-TN after a median follow-up of 74.5 months. Overall, 535 patients were randomized (acalabrutinib-obinutuzumab, n = 179; acalabrutinib, n = 179; chlorambucil-obinutuzumab, n = 177). Median age was 70 years, 63.0% had unmutated immunoglobulin heavy chain variable region gene (uIGHV), 13.6% had del(17p) and/or mutated TP53, and 17% had complex karyotype (CK; ≥3 chromosomal abnormalities). Median progression-free survival (PFS) was not reached (NR) for acalabrutinib-obinutuzumab and acalabrutinib vs 27.8 months for chlorambucil-obinutuzumab (both P < .0001); estimated 72-month overall PFS rates were 78.0%, 61.5%, and 17.2%, respectively. Acalabrutinib-obinutuzumab resulted in improved PFS vs acalabrutinib monotherapy (hazard ratio [HR], 0.58; P = .0229). Patients with uIGHV, del(17p) and/or mutated TP53, or CK had significantly improved PFS with acalabrutinib ± obinutuzumab vs chlorambucil-obinutuzumab (P < .0001, P ≤ .0009, and P < .0001 for both acalabrutinib-containing arms, respectively). Median overall survival (OS) was NR for all treatments, with significantly longer OS for acalabrutinib-obinutuzumab than chlorambucil-obinutuzumab (HR, 0.62; P = .0349). Estimated 72-month OS rates were 83.9%, 75.5%, and 74.7% for acalabrutinib-obinutuzumab, acalabrutinib, and chlorambucil-obinutuzumab, respectively. Adverse events (AEs) occurring after >4 years were mostly grade 1 to 2. Rates of AEs, serious AEs, and events of clinical interest were similar between acalabrutinib-containing arms and consistent with the known safety profiles of acalabrutinib and obinutuzumab. Efficacy and safety of acalabrutinib-containing arms were maintained, with longer PFS in both acalabrutinib arms than chlorambucil-obinutuzumab including in patients with high-risk features. This trial was registered at www.ClinicalTrials.gov as #NCT02475681.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1276-1285"},"PeriodicalIF":23.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810460","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":"Chauhan D, Li G, Hideshima T, et al. Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance. Blood. 2003;102(9):3379-3386.","authors":"","doi":"10.1182/blood.2025031044","DOIUrl":"https://doi.org/10.1182/blood.2025031044","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"42 1","pages":"1375"},"PeriodicalIF":20.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032064","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":"TE-PARPi as a precision weapon against hematologic cancers.","authors":"Eirini Trompouki","doi":"10.1182/blood.2025030226","DOIUrl":"https://doi.org/10.1182/blood.2025030226","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"35 1","pages":"1257-1259"},"PeriodicalIF":20.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032141","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}