Blood advances最新文献

{"title":"Flow MRD pre-blinatumomab consolidation, despite subsequent clearance, is associated with inferior survival in Ph+ B-ALL.","authors":"Benjamin F Frost, Yannis K Valtis, Yael Flamand, Emilie W Baxter, Shai Shimony, Jacqueline S Garcia, Martha Wadleigh, Eric S Winer, Virgina O Volpe, Maximilian Stahl, Richard M Stone, Daniel J DeAngelo, Christopher B Hergott, David Nemirovsky, Andriy Derkach, Kuo-Kai Chin, Meira Yisraeli Salman, Leora Boussi, Natalia Tijaro Ovalle, Eytan M Stein, Mark B Geyer, Yanming Zhang, Andrew M Brunner, Hanno Hock, Amir T Fathi, Rupa Narayan, Jae H Park, Marlise R Luskin, Evan C Chen","doi":"10.1182/bloodadvances.2026020724","DOIUrl":"https://doi.org/10.1182/bloodadvances.2026020724","url":null,"abstract":"<p><p>Although adults with Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (B-ALL) may achieve a measurable residual disease-negative (MRD-) complete response (CR) after frontline treatment and blinatumomab (blina) consolidation, survival outcomes are heterogeneous, and known prognostic factors are limited. We conducted a retrospective, multicenter study of 81 adults with Ph+ B-ALL in MRD- (<10-4) CR1 after blina consolidation and stratified them by pre-blina MRD status as determined by multiparametric flow cytometry (flow). Patients who were pre-blina flow MRD- (n = 56) and flow MRD+ (n = 25) had similar baseline characteristics. With a median follow-up of 31.0 months, pre-blina flow MRD- patients had superior disease-free (DFS) and overall survival (OS) on univariate (p = 0.049 and p = 0.045, respectively) and multivariable analyses (HR 0.27, 95% CI 0.08-0.87 and HR 0.17, 95% CI 0.03-0.90, respectively) relative to pre-blina flow MRD+ patients. Inferior DFS was seen with the IKZF1-plus genotype (HR 3.51, 95% CI 1.08-11.44) and extramedullary disease at diagnosis (HR 3.90, 95% CI 1.19-12.73). In exploratory analyses, pre-blina flow MRD+ status remained associated with inferior DFS (p = 0.0005) and OS (p < 0.0001) for patients who did not receive a subsequent hematopoietic cell transplant (HCT) in CR1, but not in patients who did (p = 0.55 and p = 0.99, respectively). In summary, flow MRD+ status before blina consolidation was associated with inferior survival in patients with Ph+ B-ALL in CR1 despite subsequent clearance, and consolidative HCT may reduce this prognostic effect.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191090","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":"Lipidomic reprogramming links VEGF-dependent CNS adaptation to ferroptosis sensitivity in acute lymphoblastic leukemia.","authors":"Vera Muench, Rolf Koehler, Alireza Abaei, Volker Rasche, Shuo Liu, Alexandra Niedermayer, Stefanie Enzenmüller, Aigerim Zkrina, Gudrun Strauss, Daniel Tews, Pamela Fischer-Posovszky, Johann Michael Kraus, Hans A Kestler, Klaus-Michael Debatin, Lüder Hinrich Meyer","doi":"10.1182/bloodadvances.2026020816","DOIUrl":"https://doi.org/10.1182/bloodadvances.2026020816","url":null,"abstract":"<p><p>While central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) remains a major cause of treatment failure, underlying molecular mechanisms are not fully understood. Based on previous work implicating vascular endothelial growth factor A (VEGF), we dissected its contribution to VEGF receptor 2 (VEGFR2)-mediated CNS entry versus niche-dependent survival and evaluated VEGF-targeted strategies in translational xenograft models. Using the NOD/SCID/huALL model enabling temporally defined intervention before and after CNS dissemination, bevacizumab consistently reduced established CNS ALL but had only minor effects on CNS entry, indicating a predominant contribution of VEGF in CNS ALL survival. Consistently, neither genetic depletion nor pharmacologic inhibition of murine Vegfr2 impaired transendothelial migration (TEM) in vitro. To further substantiate the role of VEGF in CNS ALL, manifest disease was treated in vivo with the multi-kinase inhibitor Sorafenib that was previously shown effective in refractory CNS leukemia patients. Sorafenib reduced CNS ALL with the highest efficacy in this compartment. In vitro, Sorafenib decreased TEM but also induced lipid peroxidation in ALL cells accompanied by ferroptosis induction. Importantly, lipidomic profiling of CNS-derived ALL cells revealed enhanced peroxidizability linked to increased ferroptosis susceptibility, providing a mechanistic link for lipid peroxidation-driven cell death in the CNS. Collectively, our findings identify VEGF signaling and lipidomic remodeling as complementary mechanisms of CNS adaptation in ALL. While VEGF supports CNS persistence, lipidomic remodeling generates a highly peroxidizable state associated with increased ferroptosis susceptibility. These findings suggest that inhibiting VEGF signaling and simultaneously inducing ferroptosis may represent a therapeutic strategy for CNS ALL.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191157","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":"Prognosis and treatment-related toxicities in Down syndrome acute lymphoblastic leukemia in JCCG ALL-B12.","authors":"Shunsuke Yamamoto, Motohiro Kato, Yuka Iijima-Yamashita, Masashi Sanada, Toshihiko Imamura, Akiko Kada, Akiko M Saito, Katsuyoshi Koh, Yasuhiro Okamoto","doi":"10.1182/bloodadvances.2026021259","DOIUrl":"https://doi.org/10.1182/bloodadvances.2026021259","url":null,"abstract":"<p><p>Children with Down syndrome (DS) have an increased risk of acute lymphoblastic leukemia (ALL). Although recent reports describe some improvement, survival in DS-ALL remains inferior to that of non-DS-ALL. This study evaluated the prognosis, relapse patterns, and treatment-related toxicities of DS-ALL in the Japan Children's Cancer Group ALL-B12 trial, a nationwide prospective study using risk-adapted therapy. A total of 1,804 patients, including 44 DS-ALL, were analyzed. Risk classification used standardized criteria. The 5-year event-free survival and overall survival in DS-ALL were 70.5% and 81.8%, respectively, lower than 85.6% and 94.6% in non-DS-ALL (P < 0.001). Survival differences were most pronounced in standard-risk patients. DS-ALL showed fewer favorable genetics and relapse patterns dominated by isolated bone marrow events, with no CNS relapse. CRLF2 rearrangement was assessable in 43 of 44 DS-ALL cases; 15 of 43 (34.9%) were positive. In an exploratory analysis excluding canonical favorable or unfavorable subtypes (n = 36), the 5-year EFS in DS-ALL with and without CRLF2 rearrangement were 57.1% and 81.8%, respectively (P = 0.300), and the corresponding 5-year OS were 78.6% and 86.4%, respectively (P = 0.331). Treatment-related toxicities were more frequent in DS-ALL, including mucositis (27.3% vs. 7.1%), hyperglycemia (25.0% vs. 6.9%), and pulmonary infections (20.5% vs. 7.4%). Among DS-ALL patients with TP2 MRD ≥ 10-4 (n = 3), all relapsed and died within three years. No treatment-related death was recorded after induction, but one death of undetermined cause occurred. These findings highlight the continuing need to optimize DS-ALL therapy to reduce relapse and toxicity. UMIN CT Registry (UMIN000009339) and JCT (jRCTs041180101).</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191250","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":"Loncastuximab and Rituximab in Elderly Unfit/Frail Patients With Previously Untreated Diffuse Large B-Cell Lymphoma.","authors":"Ranjit Nair, Abhijeet Kumar, Andrew E Chapman, Moshe Yair Levy, Jeff P Sharman, Yuvraj Choudhary, Waqas Jehangir, Jason M Melear, Andrzej Urban, Andrew Niewarowski, Luqiang Wang, Marie Toukam, John M Burke, Jason R Westin","doi":"10.1182/bloodadvances.2026020494","DOIUrl":"https://doi.org/10.1182/bloodadvances.2026020494","url":null,"abstract":"<p><p>Diffuse large B-cell lymphoma (DLBCL) therapy is typically treated with multi-agent chemotherapy with curative intent but is often challenging or poorly tolerated in patients who are elderly, frail, or have significant comorbidities. LOTIS-9 was a phase 2 trial of loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]) plus rituximab (Lonca-R) in patients with newly diagnosed DLBCL who were unfit (cohort A) or frail with or without cardiac comorbidities (cohort B), the majority of whom typically would be ineligible for trials. Patients received Lonca (150 µg/kg during cycles 1-2, 75 µg/kg for subsequent cycles) and R (375 mg/m2) intravenously Q3W for 3-6 cycles, adapted based on response after cycle 3. The primary endpoint of cohort A was complete response (CR) rate; coprimary endpoints of cohort B were CR rate and proportion of patients who completed treatment per protocol. The median age was 84 years (range, 80-91) in cohort A (n=17) and 80 years (range, 67-92) in cohort B (n=24). The CR rates were 52.9% (A: 9/17) and 41.7% (B: 10/24), respectively. In cohort B, 8 (33.3%) patients completed treatment. Grade ≥3 adverse events occurred in 31 (75.6%) patients, including 11 fatal events. Due to toxicity concerns in this medically fragile population, LOTIS-9 was voluntarily terminated prematurely though meaningful efficacy was demonstrated in patients who typically would be ineligible for clinical trials and/or standard of care therapies. These findings provide important insights for future trials. Additional investigation of targeted therapies in vulnerable unfit and frail patients with DLBCL is warranted. (ClinicalTrials.gov Identifier: NCT05144009).</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191115","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":"American Society of Hematology 2026 Guidelines for the Management of Myelofibrosis in Adults.","authors":"Brady L Stein, Maya M Abdallah, Gregory A Abel, Ghaith Abu-Zeinah, Rupali Roy Bhave, Francisca Ferrer-Marin, Arpita Gandhi, Vikas Gupta, Juan Carlos Hernandez-Boluda, Anthony Michael Hunter, Donal P McLornan, Olatoyosi Odenike, Kristen M Pettit, William Shomali, Shireen Sirhan, Andrew Srisuwananukorn, Natasha Szuber, Roni Tamari, Douglas Tremblay, Alessandro M Vannucchi, Kelley Clark, Lisa Jenkins, Bashar Hasan, Mohammad Hassan Murad","doi":"10.1182/bloodadvances.2026021650","DOIUrl":"https://doi.org/10.1182/bloodadvances.2026021650","url":null,"abstract":"<p><strong>Background: </strong>Myelofibrosis (MF) is a myeloid bone marrow malignancy with a progressive clinical course marked by disease-related symptoms, splenomegaly, cytopenias, thrombosis/hemorrhage, and a risk for blast phase transformation. Treatment recommendations are based on the burden of symptoms, prognosis of the disease, and benefits/risks of each treatment modality.</p><p><strong>Methods: </strong>ASH formed a multidisciplinary guideline panel that included specialists in myelofibrosis and hematopoietic cell transplantation, as well 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Mayo Clinic Evidence-based Practice Center supported the guideline development process, including updating or performing systematic evidence reviews (up to January 31, 2025). The panel prioritized clinical questions and outcomes according to their importance for patients and clinicians. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.</p><p><strong>Results: </strong>The panel agreed on 10 recommendations regarding prognostic testing, indications for interferon and JAK inhibitor therapy, management of MF-associated anemia, timing of transplantation, anti-platelet therapy, and iron chelation.</p><p><strong>Conclusions: </strong>Key recommendations of these guidelines include suggestions for extended molecular genetic testing; use of JAK-inhibition in symptomatic, lower risk MF patients; therapeutic strategies for patients with MF-anemia and JAK-inhibitor induced anemia; and considerations regarding hematopoietic cell transplantation including timing of referral and optimization prior to the procedure. Key future research agendas were identified for all recommendations.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179512","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":"Cost comparison of pdVWF/FVIII prophylaxis and on-demand therapy in type 3 von Willebrand disease in the United States.","authors":"Robert F Sidonio, Nathan T Connell, Fernando F Corrales-Medina, Roberta Longo, Wei-Shi Yeh, Caroline Malcolmson","doi":"10.1182/bloodadvances.2026019994","DOIUrl":"10.1182/bloodadvances.2026019994","url":null,"abstract":"<p><strong>Abstract: </strong>Von Willebrand factor (VWF) concentrate prophylaxis is recommended for patients with severe von Willebrand disease (VWD) or VWD with frequent bleeding symptoms but remains underused due, in part, to the high direct cost associated with regular concentrate administration. Robust cost-effectiveness data for VWF prophylaxis are limited, with most analyses relying on literature-based assumptions rather than prospective clinical data. A trial-based cost-effectiveness analysis was developed to estimate the long-term economic impact of plasma-derived VWF/factor VIII (Wilate) prophylaxis vs on-demand therapy in patients with type 3 VWD in the United States, from both payer and societal perspectives. Clinical inputs were derived directly from phase 3 clinical studies, whereas health care costs were obtained from published sources. Productivity losses during bleeding events were incorporated into the societal analysis. Subgroup analyses were performed for adults and adult women with type 3 VWD, and evaluations were conducted for both 1-year and lifetime horizons. The payer analysis highlighted potential cost savings with Wilate prophylaxis across all groups, with estimated annual savings of $10 898 per individual in the overall type 3 VWD cohort, $53 264 among adults, and $125 712 among women. Savings were higher in the societal perspective, with the largest benefit observed in women ($148 555 per individual annually). The primary cost drivers were bleeding rates and treatment costs during on-demand therapy. In addition to its established clinical efficacy, these findings demonstrate a potential substantial economic advantage of Wilate prophylaxis and support broader adoption of VWF-based prophylaxis for individuals with type 3 VWD in the United States.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"6719-6728"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel humanized FIX/FX hemophilia A mouse model for preclinical evaluation of FVIIIa-mimetic bispecific antibodies.","authors":"Tomoyuki Watanabe, Asuka Sakata, Naoki Matsumoto, Suguru Harada, Satoshi Yamamoto, Otoya Ueda, Tetsuhiro Soeda, Kohei Tatsumi, Midori Shima, Keiji Nogami","doi":"10.1182/bloodadvances.2025018528","DOIUrl":"10.1182/bloodadvances.2025018528","url":null,"abstract":"<p><strong>Abstract: </strong>The use of nonfactor products such as emicizumab, a bispecific antibody that mimics the cofactor function of activated factor VIII (FVIIIa) by bridging FIXa and FX, has significantly reduced bleeding episodes in people with hemophilia A (HA). However, emicizumab high species specificity in its FVIIIa-mimetic cofactor activity has limited in vivo functional evaluation to an acquired HA nonhuman primate model or congenital HA mouse model with infusion of human FIX (hFIX) and hFX proteins. To overcome the limitations of existing models, we generated hFIX/hFX double-knockin congenital HA model (humanized HA [HuHA]) mice. HuHA mice were established by the replacement of mouse FIX/FX genes with their human homologs and by the disruption of mouse FVIII. In HuHA mice, functional hFIX and hFX are constitutively expressed at levels equivalent to, or higher than, human plasma concentrations. Thrombin generation assays demonstrated dose dependently improved peak thrombin generation by both recombinant hFVIII (rhFVIII) and emicizumab. These HuHA mice were found to express sufficient levels of hFIX and hFX to support functional evaluation of rhFVIII and emicizumab activities. Furthermore, the tail-clip assay suggested potential hemostatic effects of both therapeutic agents in vivo, although the findings should be interpreted with caution given the limitations of the model. This novel mouse model, in which functional hFIX and hFX are constitutively expressed on an FVIII-deficient background, may provide a new platform for the preclinical evaluation of human-specific therapeutics for HA.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"6685-6693"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CC-486 plus venetoclax: another step toward oral AML therapy.","authors":"Kimberly Seymour, Marina Konopleva","doi":"10.1182/bloodadvances.2026021747","DOIUrl":"10.1182/bloodadvances.2026021747","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"10 19","pages":"6683-6684"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The roots run deep in therapy-related myeloid neoplasms.","authors":"Maria Creignou, Elsa Bernard","doi":"10.1182/bloodadvances.2026021682","DOIUrl":"10.1182/bloodadvances.2026021682","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"10 19","pages":"6768-6770"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMA + venetoclax triplet regimens for the initial treatment of AML in adults.","authors":"Maximilian Stahl, Richard M Stone","doi":"10.1182/bloodadvances.2025018556","DOIUrl":"10.1182/bloodadvances.2025018556","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"6637-6640"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}