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Characterization of hematopoietic stem cell-derived microglia-like cells in nonhuman primates. 非人灵长类动物造血干细胞衍生的小胶质样细胞的表征。
IF 7.7 1区 医学
Blood advances Pub Date : 2026-10-13 DOI: 10.1182/bloodadvances.2025019337
Nicholas E Petty, Carl B Wolf, Greta Kanestrom, Mark Mendoza, Kyle Swing, Robert Murnane, Alvin Tong, Marlena Starrs, Emily Fields, Ravishankar Madhu, Veronica Nelson, Frederick C Bennett, Scott Furlan, Keith Loeb, Stefan Radtke, Hans-Peter Kiem
{"title":"Characterization of hematopoietic stem cell-derived microglia-like cells in nonhuman primates.","authors":"Nicholas E Petty, Carl B Wolf, Greta Kanestrom, Mark Mendoza, Kyle Swing, Robert Murnane, Alvin Tong, Marlena Starrs, Emily Fields, Ravishankar Madhu, Veronica Nelson, Frederick C Bennett, Scott Furlan, Keith Loeb, Stefan Radtke, Hans-Peter Kiem","doi":"10.1182/bloodadvances.2025019337","DOIUrl":"10.1182/bloodadvances.2025019337","url":null,"abstract":"<p><strong>Abstract: </strong>Hematopoietic stem cell transplantation (HSCT) is the current standard of care for several neurotrophic lysosomal storage disorders. The therapeutic mechanism of HSCT is believed to be mediated by the engraftment of hematopoietic stem cell progeny into the brain as microglia-like cells (MLCs). However, the engraftment of MLCs and their transcriptomic identity relative to endogenous microglia remain poorly understood. In this study, we used an autologous nonhuman primate (NHP) HSCT model to investigate the engraftment of MLCs after gene-modified autologous HSCT. We observed engraftment of gene-marked MLCs across a cohort of 5 NHPs. MLCs engrafted throughout diverse brain regions, adopted a homeostatic ramified morphology, and upregulated core microglial transcripts. We then used single-cell RNA sequencing to more rigorously evaluate the transcriptome of MLCs, revealing a border-associated macrophage-like phenotype. Our findings offer critical insights into the engraftment and behavior of MLCs after HSCT, laying the groundwork for their future use as a directed therapeutic option.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"6359-6365"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276209","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}
引用次数: 0
Burkitt lymphoma: current understanding, unmet needs, and research directions. 伯基特淋巴瘤:目前的认识,未满足的需求和研究方向。
IF 7.7 1区 医学
Blood advances Pub Date : 2026-10-13 DOI: 10.1182/bloodadvances.2024015620
Adiba Khan, Cristina López, Suzanne D Turner, Sam M Mbulaiteye
{"title":"Burkitt lymphoma: current understanding, unmet needs, and research directions.","authors":"Adiba Khan, Cristina López, Suzanne D Turner, Sam M Mbulaiteye","doi":"10.1182/bloodadvances.2024015620","DOIUrl":"10.1182/bloodadvances.2024015620","url":null,"abstract":"<p><strong>Abstract: </strong>Burkitt lymphoma (BL) is an aggressive B-cell lymphoma historically classified into endemic, sporadic, or immunodeficiency-associated BL based on clinical and epidemiological features. Recent genomic and epigenomic studies have refined this framework, distinguishing Epstein-Barr virus (EBV)-positive and EBV-negative BL molecular subtypes that cut across traditional clinical and epidemiological categories and exhibit distinct biological profiles. In high-income countries (HICs), BL is highly curable with intensive multiagent chemotherapy and antibody-based therapy. In contrast, survival in sub-Saharan Africa rarely exceeds 50%, reflecting diagnostic delays, limited access to effective treatment, and challenges in supportive care. This review summarizes the advances in BL epidemiology, molecular biology, diagnosis, and treatment, highlighting how genomic insights have identified novel biomarkers for earlier detection and monitoring, as well as potential targeted therapies with reduced toxicity. These advances present opportunities to develop scalable diagnostic tools and tailored therapeutic strategies to narrow survival disparities, particularly in resource-limited settings, where most patients occur, and among adults and patients with relapsed or refractory BL in HICs. We also outline key unanswered questions in BL epidemiology and pathogenesis, discuss opportunities for translational research, and emphasize the need for improved model systems to study therapeutic resistance to close the survival gap.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"6796-6811"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444584","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}
引用次数: 0
Rapid and reproducible karyotyping with long-read sequencing in patients with AML. AML患者的长读序列快速可重复核型分析。
IF 7.7 1区 医学
Blood advances Pub Date : 2026-10-13 DOI: 10.1182/bloodadvances.2026019960
Michael Heuser, Anna Dolnik, Isabell Arnhardt, Courteney K Lai, Ekaterina Jahn, Mustafa Salim, Gudrun Göhring, Yvonne Lisa Behrens, Jonathan L Lühmann, Doris Steinemann, Martin Wichmann, Jens Florian Schrezenmeier, Yasmine Alwie, Arnold Kloos, Gesa Baurmann, Jörg Westermann, Frederik Damm, Hartmut Döhner, Arnold Ganser, Felicitas R Thol, Olga Blau, Konstanze Döhner, Lars Bullinger, Razif Gabdoulline, Jan Eric Sträng
{"title":"Rapid and reproducible karyotyping with long-read sequencing in patients with AML.","authors":"Michael Heuser, Anna Dolnik, Isabell Arnhardt, Courteney K Lai, Ekaterina Jahn, Mustafa Salim, Gudrun Göhring, Yvonne Lisa Behrens, Jonathan L Lühmann, Doris Steinemann, Martin Wichmann, Jens Florian Schrezenmeier, Yasmine Alwie, Arnold Kloos, Gesa Baurmann, Jörg Westermann, Frederik Damm, Hartmut Döhner, Arnold Ganser, Felicitas R Thol, Olga Blau, Konstanze Döhner, Lars Bullinger, Razif Gabdoulline, Jan Eric Sträng","doi":"10.1182/bloodadvances.2026019960","DOIUrl":"10.1182/bloodadvances.2026019960","url":null,"abstract":"<p><strong>Abstract: </strong>Acute myeloid leukemia (AML) is characterized by recurrent chromosomal abnormalities that form the basis of the European LeukemiaNet risk classification and serve as essential determinants of prognosis and therapeutic decision-making. Conventional metaphase karyotyping remains the diagnostic gold standard for detecting these abnormalities; however, its utility is limited by longer turnaround times, often delaying critical clinical management. Here, we present a long-read, low-coverage whole-genome sequencing (lcWGS) approach using Oxford Nanopore Technology as a rapid and scalable alternative for cytogenetic profiling. A total of 100 diagnostic AML samples were analyzed, comprising 50 retrospectively selected patients with known adverse-risk cytogenetics and 50 prospectively enrolled patients with clinically defined de novo AML. LcWGS demonstrated robust analytical performance, identifying chromosomal aberrations with 93% sensitivity, specificity, and overall accuracy, respectively. Complex karyotypes were reliably detected, with an area under the curve of 0.971. Reproducibility was validated through replicate sequencing at 2 independent laboratories (R = 0.99). LcWGS-derived estimates of clone size showed moderate correlation with conventional cytogenetic assessments (R = 0.54). Patients with complex karyotypes identified by lcWGS exhibited significantly shorter overall and relapse-free survival, closely mirroring outcomes defined by conventional karyotyping and underscoring the value of lcWGS for risk stratification. The median turnaround time from sample receipt to bioinformatics interpretation was ∼34 hours, enabling delivery of actionable karyotype results within 72 hours. These findings establish lcWGS as a rapid, reproducible, and accurate platform for detecting clinically relevant chromosomal abnormalities, addressing a critical need for timely risk stratification and treatment initiation in AML.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"6774-6784"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148326817","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}
引用次数: 0
In vivo and ex vivo impact of THBD and PROCR polymorphisms on the anticoagulant response of the protein C pathway. 体内和体外THBD和PROCR多态性对蛋白C途径抗凝反应的影响。
IF 7.7 1区 医学
Blood advances Pub Date : 2026-10-13 DOI: 10.1182/bloodadvances.2025018733
Sara Reda, Nadine Schwarz, Sebastian F Eckert, Jens Müller, Johannes Oldenburg, Bernd Pötzsch, Behnaz Pezeshkpoor, Heiko Rühl
{"title":"In vivo and ex vivo impact of THBD and PROCR polymorphisms on the anticoagulant response of the protein C pathway.","authors":"Sara Reda, Nadine Schwarz, Sebastian F Eckert, Jens Müller, Johannes Oldenburg, Bernd Pötzsch, Behnaz Pezeshkpoor, Heiko Rühl","doi":"10.1182/bloodadvances.2025018733","DOIUrl":"10.1182/bloodadvances.2025018733","url":null,"abstract":"<p><strong>Abstract: </strong>Venous thromboembolism (VTE) is multifactorial, and established hereditary risk factors explain only part of heritable risk. The protein C (PC) pathway is central to anticoagulant control, and common variants in thrombomodulin and endothelial PC receptor genes (THBD, PROCR) have been proposed as modulators. In 73 participants, we used standardized in vivo coagulation activation with recombinant activated factor VII (15 μg/kg) and measured thrombin markers and activated PC (APC) over 8 hours. Endothelial colony-forming cell-based ex vivo experiments were performed in 43 participants. In vivo, the ratio of APC area under the curve (AUC) to thrombin-antithrombin complex (TAT) AUC, which reflects the endogenous anticoagulant response relative to thrombin generation, provided the best model fit (adjusted R2 = 0.345). The APC response was lower in individuals with previous VTE (median, 0.13 vs 0.26) and PROCR 655A>G carriers (0.11 vs 0.26), but higher in factor V Leiden (FVL) carriers (0.32 vs 0.14) and THBD 1418C>T carriers (0.38 vs 0.13). The THBD 1418C>T effect was driven by reduced TAT AUC (30.6 vs 82.7 pmol × h/L), whereas the PROCR 655A>G effect reflected a lower APC AUC (8.6 vs 10.7 pmol × h/L). Ex vivo, the APC AUC/thrombin AUC ratio was lower with previous VTE and PROCR 655A>G, higher with FVL, and not associated with THBD 1418C>T. No in vivo or ex vivo association was observed for PROCR 4678C>G. This study provides in vivo evidence that common THBD and PROCR variants modulate PC pathway function, establishing the APC response as a sensitive end point for subtle genetic effects beyond FVL.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"6818-6827"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547980","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}
引用次数: 0
Hydroxyurea reduces hyperadhesion measured by a VLA-4-targeting PET tracer in sickle transgenic Townes mice. 羟基脲降低了镰刀转基因Townes小鼠的高黏附,用一种靶向PET示踪剂测定。
IF 7.7 1区 医学
Blood advances Pub Date : 2026-10-13 DOI: 10.1182/bloodadvances.2025019423
Nishi Yadav, Qin Zhu, Lynda Little-Ihrig, Joseph D Latoche, Kathryn E Day, Kanishka Sikligar, Sina Tavakoli, Enrico M Novelli, Carolyn J Anderson
{"title":"Hydroxyurea reduces hyperadhesion measured by a VLA-4-targeting PET tracer in sickle transgenic Townes mice.","authors":"Nishi Yadav, Qin Zhu, Lynda Little-Ihrig, Joseph D Latoche, Kathryn E Day, Kanishka Sikligar, Sina Tavakoli, Enrico M Novelli, Carolyn J Anderson","doi":"10.1182/bloodadvances.2025019423","DOIUrl":"10.1182/bloodadvances.2025019423","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"6764-6767"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509138","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}
引用次数: 0
Germ line landscape stratification defines distinct molecular and prognostic groups in therapy-related myeloid neoplasms. 种系景观分层在治疗相关髓系肿瘤中定义了不同的分子和预后组。
IF 7.7 1区 医学
Blood advances Pub Date : 2026-10-13 DOI: 10.1182/bloodadvances.2026020704
Oriol Calvete, Julia Mestre, Lorea Chaparro-González, Lucía Ruiz Pérez-Hita, Alba Mesa, Blanca Xicoy, Lurdes Zamora, Isabel Granada, Mar Mallo, Emili Cid, Estefania Mancini, Claudia Lozano, Laura Palomo, Pamela Acha, María Julia Montoro, Koji Sasaki, Courtney DiNardo, Guillermo Garcia-Manero, Guillermo Montalban-Bravo, Neus Torres-Hernández, Marta Santiago-Balsera, José Cervera, Gonzalo Maortua, Raquel de Paz, Martí Mascaró, Alfonso García Da Vila, Sara García-Ávila, Juan José Rodriguez-Sevilla, Leonor Arenillas, Beatriz Bellosillo, Rashmi Kanagal-Shamanna, Francesc Solé
{"title":"Germ line landscape stratification defines distinct molecular and prognostic groups in therapy-related myeloid neoplasms.","authors":"Oriol Calvete, Julia Mestre, Lorea Chaparro-González, Lucía Ruiz Pérez-Hita, Alba Mesa, Blanca Xicoy, Lurdes Zamora, Isabel Granada, Mar Mallo, Emili Cid, Estefania Mancini, Claudia Lozano, Laura Palomo, Pamela Acha, María Julia Montoro, Koji Sasaki, Courtney DiNardo, Guillermo Garcia-Manero, Guillermo Montalban-Bravo, Neus Torres-Hernández, Marta Santiago-Balsera, José Cervera, Gonzalo Maortua, Raquel de Paz, Martí Mascaró, Alfonso García Da Vila, Sara García-Ávila, Juan José Rodriguez-Sevilla, Leonor Arenillas, Beatriz Bellosillo, Rashmi Kanagal-Shamanna, Francesc Solé","doi":"10.1182/bloodadvances.2026020704","DOIUrl":"10.1182/bloodadvances.2026020704","url":null,"abstract":"<p><strong>Abstract: </strong>Exposure to chemotherapy (CT) and/or radiotherapy increases the risk of therapy-related myeloid neoplasms (t-MN), a heterogeneous group of disorders currently classified by treatment history rather than molecular features. Although germ line predisposition has been suggested in ∼20% of patients, its prevalence and clinical impact remain insufficiently defined. To address this, we analyzed 100 patients with t-MN by integrating clinical characteristics, prior treatment regimens, and genomic profiling. Somatic and germ line variants were identified using targeted next-generation sequencing (n = 33) or whole-exome sequencing (n = 67). Somatic abnormalities, including cytogenetic and/or molecular alterations, were detected in 89.8% of patients. Germ line variants were identified in 32.3% of patients, including mutations in cancer predisposition genes (19.8%) and myeloid disease-related genes (14.6%). Patient stratification by germ line landscape and gene category defined 2 prognostic scenarios and 3 subgroups with distinct clinical outcomes. Patients harboring germ line cancer predisposition variants were enriched for TP53 mutations and complex karyotypes and had an adverse prognosis. In contrast, patients with germ line myeloid-related variants and those without detectable germ line variants exhibited recurrent mutations in TET2, DNMT3A, SF3B1, SRSF2, RUNX1, and ASXL1, were associated with normal karyotypes, and had favorable outcomes. These findings underscore the importance of the germ line landscape in t-MN pathogenesis and support its incorporation into disease classification and risk stratification. Notably, CT exposure was associated with complex karyotypes and poor prognosis in patients with germ line cancer predisposition variants, highlighting a subgroup that may benefit from targeted surveillance and preventive strategies.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"6703-6718"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418920","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}
引用次数: 0
Are statins interferon's best friends? Mechanistic insights. 他汀类药物是干扰素最好的朋友吗?机械的见解。
IF 7.7 1区 医学
Blood advances Pub Date : 2026-10-13 DOI: 10.1182/bloodadvances.2026020672
Giacomo Maria Cerreto, Cecilia Carubbi, Marco Vitale, Elena Masselli
{"title":"Are statins interferon's best friends? Mechanistic insights.","authors":"Giacomo Maria Cerreto, Cecilia Carubbi, Marco Vitale, Elena Masselli","doi":"10.1182/bloodadvances.2026020672","DOIUrl":"10.1182/bloodadvances.2026020672","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"6845-6848"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155179","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}
引用次数: 0
Canadian emicizumab registry: a blueprint for the future. 加拿大emicizumab注册:未来的蓝图。
IF 7.7 1区 医学
Blood advances Pub Date : 2026-10-13 DOI: 10.1182/bloodadvances.2026021680
Cedric Hermans
{"title":"Canadian emicizumab registry: a blueprint for the future.","authors":"Cedric Hermans","doi":"10.1182/bloodadvances.2026021680","DOIUrl":"10.1182/bloodadvances.2026021680","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"10 19","pages":"6860-6861"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179464","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}
引用次数: 0
Chronic graft-versus-host disease after PTCy-based prophylaxis vs non-PTCy prophylaxis. 基于环磷酰胺(PTCy)预防与非PTCy预防的移植后慢性移植物抗宿主病
IF 7.7 1区 医学
Blood advances Pub Date : 2026-10-13 DOI: 10.1182/bloodadvances.2026020655
Joseph Pidala, Jongphil Kim, Jose Laborde, Samantha Knott, Krishnakar Mogili, Justin Zinn, Alicia Monroe, Rawan Faramand, Reshma Ramlal, Farhad Khimani, Doris K Hansen, Nancy Torres-Luna, Michael D Jain, Lia E Perez, Asmita Mishra, Nima Ghalehsari, Omar Castaneda-Puglianini, Melissa Alsina, Fabiana Perna, Michael Nieder, Abu-Sayeef Mirza, Hien Liu, Taiga Nishihori, Alaa Ali, Deepak Chellapandian, Frederick L Locke, Nelli Bejanyan, Claudio Anasetti, Aleksandr Lazaryan
{"title":"Chronic graft-versus-host disease after PTCy-based prophylaxis vs non-PTCy prophylaxis.","authors":"Joseph Pidala, Jongphil Kim, Jose Laborde, Samantha Knott, Krishnakar Mogili, Justin Zinn, Alicia Monroe, Rawan Faramand, Reshma Ramlal, Farhad Khimani, Doris K Hansen, Nancy Torres-Luna, Michael D Jain, Lia E Perez, Asmita Mishra, Nima Ghalehsari, Omar Castaneda-Puglianini, Melissa Alsina, Fabiana Perna, Michael Nieder, Abu-Sayeef Mirza, Hien Liu, Taiga Nishihori, Alaa Ali, Deepak Chellapandian, Frederick L Locke, Nelli Bejanyan, Claudio Anasetti, Aleksandr Lazaryan","doi":"10.1182/bloodadvances.2026020655","DOIUrl":"10.1182/bloodadvances.2026020655","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic graft-versus-host disease (GVHD) is less frequent after posttransplant cyclophosphamide (PTCy)-based prophylaxis, but its clinical characteristics and outcomes compared with chronic GVHD after non-PTCy approaches remain understudied. We addressed this through a single-center retrospective study of 1534 consecutive adult transplant recipients (PTCy, n = 477; non-PTCy, n = 1057) who received grafts from matched related or matched/mismatched unrelated donors. The cumulative incidence of National Institutes of Health (NIH) moderate/severe chronic GVHD was significantly lower after PTCy (17% vs 46%; P< .001). Among patients with chronic GVHD (PTCy, n = 163; non-PTCy, n = 656), chronic GVHD after PTCy involved fewer organ sites, had lower severity scores, and had less NIH moderate/severe disease overall. However, this profile did not translate into improved survival. Univariate analysis demonstrated higher nonrelapse mortality (NRM; 24-month NRM, 22% vs 13%; P = .014) for the PTCy group, whereas multivariate analysis showed that NRM was associated with increased age, NIH overall moderate/severe chronic GVHD severity, prior grade III/IV acute GVHD, reduced platelet count, and increased bilirubin. Chronic GVHD after PTCy was associated with increased infectious complications despite reduced immunosuppressive (IS) therapy and higher rates of complete IS discontinuation. Overall, PTCy-based prophylaxis was associated with a lower incidence and severity of chronic GVHD, and after adjustment for established prognostic factors, mortality after chronic GVHD diagnosis was comparable to that observed with non-PTCy prophylaxis approaches. Multicenter validation of these findings and novel strategies to mitigate NRM in chronic GVHD are warranted.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"6598-6609"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547906","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}
引用次数: 0
A phase 1b/2 study of ceralasertib, a selective inhibitor of ATR, in patients with relapsed or refractory MDS and CMML. 一项针对复发或难治性MDS和CMML患者的选择性ATR抑制剂ceralasertib Ib/II期研究。
IF 7.7 1区 医学
Blood advances Pub Date : 2026-10-13 DOI: 10.1182/bloodadvances.2026019848
Andrew M Brunner, Yiwen Liu, Jacqueline S Garcia, Lourdes Mendez, Catherine Gutierrez Moore, Sridhar Nonavinkere Srivatsan, Jin Shao, Brandon J Aubrey, Philip Amrein, Rupa Narayan, Rahul Vedula, Eliana Friedman, Donna Neuberg, Marcio Andrade-Campos, Simon A Smith, Richard Stone, Amir T Fathi, Matthew J Walter, Timothy A Graubert, Meagan A Jacoby
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