Blood advances最新文献

{"title":"Immune cells display an abnormal maturation and a pro-inflammatory profile in telomere biology disorders.","authors":"Willian R Gomes, Shan Hama, Giorgio Napolitani, Amandine Tan, Luiz Fernando B Catto, Flavia S Donaires, Barbara A Santana, Vinicius S Carvalho, Edson Z Martinez, Antonio Condino-Neto, Mohammad M Karimi, Ghulam J Mufti, Rodrigo T Calado","doi":"10.1182/bloodadvances.2025015976","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025015976","url":null,"abstract":"<p><p>Pathogenic germline variants causing excessive telomere shortening may result in bone marrow failure, hematopoietic malignancy, and extramedullary complications, such as pulmonary fibrosis, liver cirrhosis, and solid tumors. Patients with short telomeres also develop immunodeficiency with low CD4+ T cells and impaired general immunosurveillance, particularly against solid neoplasms. We investigated a broad spectrum of lymphocyte subsets and myeloid immune cells from human patients with telomere biology disorders (TBDs) and matched healthy volunteers to understand further how the immune system is affected by telomere dysfunction. We employed mass cytometry (CyTOF) for deep-immunophenotyping peripheral blood mononuclear cells (PBMCs), followed by high-dimensional data analysis. Cytokines, chemokines, and growth factors were assessed in serum. Our results showed profound immune alterations in TBD beyond those observed in aging, with low naïve lymphocytes and thymic hypofunction. We further observed that T helper subsets were markedly skewed, with an inverted TH2/TH1 ratio and low TH17 and TH17.1 levels. T cell activation and exhaustion markers were upregulated, whereas circulating mucosal-associated invariant T (MAIT) cells were significantly decreased and overactivated. Several serum cytokine levels were positively correlated with telomere length and blood counts, suggesting an association with marrow function. In aggregate, these findings suggest a pro-inflammatory profile in TBDs. Our data provide new details on how TBD affects immune cells, particularly lymphocytes, which may contribute to the clinical phenotypes.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648537","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":"Estimating efficacy of favezelimab plus pembrolizumab relative to pembrolizumab in anti-PD-1-refractory Hodgkin lymphoma.","authors":"Philippe Armand, Pier Luigi Zinzani, John M Timmerman, Nathalie A Johnson, David Lavie, Kannan Thiagarajan, Brian Topp, Pallavi M Pillai, Alex F Herrera","doi":"10.1182/bloodadvances.2024014654","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014654","url":null,"abstract":"<p><p>Favezelimab plus pembrolizumab had promising efficacy in anti-PD-1-refractory classical Hodgkin lymphoma in MK-4280-003; however, the contribution of favezelimab was unclear. Here, we assessed the relative contribution of favezelimab by comparison with data from participants treated with only pembrolizumab beyond progression in KEYNOTE-087. Participants in MK-4280-003 had received ≥2 doses of anti-PD-1 therapy and progressed <12 weeks of last dose. Participants eligible from KEYNOTE-087 had received >2 doses of pembrolizumab beyond progression and progressed <12 weeks of last dose. Participants received pembrolizumab 200 mg plus favezelimab 200 mg or 800 mg or pembrolizumab 200 mg intravenously every 3 weeks. Change in target lesion size and response per International Working Group 2007 criteria were assessed. Baseline tumor size was reset at first progression for KEYNOTE-087. A bootstrapping method compared change in target lesion size between groups. Twenty-seven participants from MK-4280-003 and 81 from KEYNOTE-087 were included. Objective response rates were 37% (95% CI, 15-51) for favezelimab plus pembrolizumab and 2% (95% CI, 0-6) for pembrolizumab alone. A clinically meaningful reduction (≥50%) in target lesion size was observed in 13 (48%) vs 4 (5%) participants, respectively. Mean change from baseline in target lesion size was -49% and -0.4%. In the bootstrapping analysis, 99.4% of samples showed greater decrease in tumor burden with favezelimab plus pembrolizumab. Favezelimab plus pembrolizumab had a higher response rate and greater reduction in tumor burden vs pembrolizumab alone in anti-PD-1-refractory classical Hodgkin lymphoma, suggesting favezelimab contributed substantially to efficacy in MK-4280-003. NCT03598608, NCT02453594.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648535","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":"TAFASITAMAB PLUS LENALIDOMIDE AS SALVAGE THERAPY IN DIFFUSE LARGE B-CELL LYMPHOMA: REAL-WORLD EXPERIENCE FROM GELTAMO.","authors":"Antonio Gutierrez, Izaskun Zeberio, Francisco Javier Penalvar, Pilar Martinez-Barranco, Sandra Perez, Daniel Morillo, Xabier Martin, Concepción Nicolás, Ainara Ferrero, Ana Jiménez-Ubieto, Mariana Bastos-Oreiro, Julio Davila-Valls, Maria Victoria Calle Gordo, María Pérez Sala, Guillermo Rodriguez, Aranzazu Alonso, Ana Garcia-Noblejas, Diana Sanchez-Arguello, Teresa Knight, Angeles Fernandez, Javier López-Marín, Jaime Perez de Oteyza, Sonia Gonzalez de Villambrosia, Elena Pérez, Alejandro Marin, Maria Belen Navarro, Rubén Fernández, Pilar Gómez-Prieto, Jose Antonio Hueso, Maria Jesus Peñarrubia, Pilar Bravo, Daniel García Belmonte, Haridian De la Nuez, Sara Nistal, Pau Abrisqueta, Fernanda Ibañez, Luis Palomera Bernal, Eva Donato, Andrea Provencio, Maria Stefania Infante, Eva González Barca","doi":"10.1182/bloodadvances.2025016661","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016661","url":null,"abstract":"<p><p>Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) remains challenging to treat, especially in patients ineligible for intensive therapy or CAR-Ts. Tafasitamab plus lenalidomide (T/L) is an effective option based on the phase 2 L-MIND trial findings, although real-world evidence studies have not consistently confirmed these results. We aimed to describe real-world outcomes of R/R DLBCL treated with T/L in Spain. A total of 99 patients received at least one dose of tafasitamab (ITT cohort), with 83 completing at least one full cycle of T/L (efficacy cohort). Respectively for ITT and efficacy cohorts, at a median follow-up of 19.2 and 21.6 months, the overall response rate was 51% and 61% (CR: 35% and 42%). Median duration of response was not reached, and patients achieving a CR had excellent outcomes. The median PFS were 4.9 and 10.9 months, and overall survival (OS) were 12.2 and 21.8 months, respectively for both ITT and efficacy cohorts. Neither age nor CIRS influenced survival. Better PFS was obtained in first/second relapse but only poor ECOG PS 2-4 (HR 2.1), double-hit lymphoma (HR 2.5) and those with refractory/progressing disease after the previous therapy (HR 2.1), were independently associated with worse PFS. Treatment was generally well-tolerated, with manageable toxicity. Relative dose-intensity (RDI) of lenalidomide significantly affected response, PFS and OS. In summary, T/L is both well-tolerated and effective, irrespective of age or comorbidities. Our findings provide valuable insights into the real-world application of T/L and reinforce its role as a key treatment option for patients with R/R DLBCL.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641845","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":"The immune receptor FcRg-chain mediates CD36-induced platelet activation and thrombosis by oxidised low-density lipoproteins.","authors":"Katie S Wraith, Jawad S Khalil, Ahmed Aburima, Lih Tyng Cheah, Matthew S Hindle, Martin Berger, Romez Uddin, Hoor Ayub, Mary McKay, Rui-Gang Xu, Robert A S Ariëns, Mark T Kearney, Michael G Tomlinson, Khalid M Naseem","doi":"10.1182/bloodadvances.2024015652","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015652","url":null,"abstract":"<p><p>The scavenger receptor CD36 links atherogenic dyslipidaemia to platelet hyperactivity and accelerated thrombosis through the binding of oxidised low-density lipoproteins (oxLDL). The signalling mechanism(s) that facilitates CD36 translation of oxidative lipid stress into platelet activation is unclear. We examined the role of immunoreceptor tyrosine-based activation motif (ITAM) adaptor proteins in CD36-mediated platelet activity. OxLDL induced the phosphorylation of the ITAM-containing adaptor FcRg-chain (FcRg) in human and murine platelets. Phosphorylation of FcRg was blocked by Src Family Kinase (SFK) inhibitors, mimicked by CD36-specific oxidised phospholipids and ablated in CD36-/- murine platelets. Under basal conditions, a pool of CD36 formed a multiprotein complex that included FcRg and the SFKs Lyn and Fyn. CD36 ligation by oxLDL resulted in the recruitment, phosphorylation and activation of the tyrosine kinase Syk. To explore the functional cooperativity of this CD36-FcRg complex, we used murine platelets deficient in FcRg. The genetic ablation of FcRg prevented oxLDL-induced tyrosine phosphorylation of Syk and downstream adapter SLP-76, but not SFKs. Moreover, platelet aggregation, in vitro thrombosis, and in vivo carotid thrombosis stimulated by oxLDL were lost in the absence of FcRg. This study establishes FcRg as a first functional co-receptor for CD36 in platelets, which enables lipid platelet hyperactivity and arterial thrombosis.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641847","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":"Dietary Tryptophan Augments Cancer-Associated Venous Thrombosis Mitigated by Indoleamine 2,3-Dioxygenase 1 Inhibition.","authors":"Saran Lotfollahzadeh, Asha Jose, Xiaosheng Yang, Tanvi Bathla, Adam Lazowski, Isaac Hoekstra, Kashvi Sethuraman, Sowmya Potluri, Karlynn Dulberger, Jennifer La, Nathanael Fillmore, Maria Del Carmen Piqueras, Norman Lee, Howard J Cabral, Katya Ravid, Vipul Chitalia","doi":"10.1182/bloodadvances.2025017079","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025017079","url":null,"abstract":"<p><p>Studies related to cardio-oncology remain of high priority, considering that venous thromboembolism (VTE) in cancer survivors is the second most common cause of death. While diet-derived metabolites are emerging contributors to VTE, the influence of specific dietary components, their underlying mechanisms, and means to mitigate cancer-associated VTE remain poorly investigated. This point is important as population studies point to a protein-rich diet associated with VTE. Leveraging a new colon cancer-VTE mouse model, we show that an imbalanced protein-rich diet augments venous thrombogenicity in tumor-bearing mice. Further probing showed that tryptophan in the diet induces a procoagulant venous wall characterized by the upregulation of tissue factor, plasminogen activator inhibitor-1 and von Willebrand Factor, and downregulation of thrombomodulin. Targeted metabolomics of sera from tumor-bearing mice revealed a pattern consistent with increased biogenesis of kynurenine (Kyn) and its suppressed catabolism, despite equal diet consumption in all groups. Kyn levels positively correlated with venous clots. Indolamine-2,3-dioxygenase (IDO1) is a key rate-limiting enzyme converting tryptophan to Kyn. Sera and the inferior vena cava of tumor-bearing mice showed greater IDO1 activity and protein level, respectively. A specific IDO1 inhibitor reduced serum levels of Kyn, restored the balance of pro- and anti-coagulant factors in the venous endothelium, and significantly suppressed venous thrombogenicity in tumor-bearing mice. Taken together, our results uncovered a prothrombotic effect of a protein or tryptophan-rich diet in a syngeneic colon cancer model, which is significantly attenuated by an IDO1 inhibitor.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641771","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":"Population-based validation of the CAR-HEMATOTOX for hematotoxicity, infections and survival after CART in R/R LBCL.","authors":"Janneke W de Boer, Kylie Keijzer, Suzanne van Dorp, Pim G N J Mutsaers, Anne Gh Niezink, Jaap A van Doesum, Yasmina Im Serroukh, Louise W Muntendam, Astrid E Pulles, Esther J Kret, Aniko Sijs-Szabo, Jesse Oomen, Astrid Mp Demandt, Wendy Bc Stevens, Maria T Kuipers, Elise Ra Pennings, Anne Mea Spanjaart, Marie José Kersten, Margot Jak, Lisanne Vania van Dijk, Marjolein Wm van der Poel, Joost Sp Vermaat, Tom van van Meerten","doi":"10.1182/bloodadvances.2025016689","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016689","url":null,"abstract":"<p><p>Early identification of patients at risk for immune effector cell-associated hematotoxicity (ICAHT) is essential to minimize non-relapse mortality. The CAR-HEMATOTOX (HT) score is an implemented risk-stratification tool for ICAHT, infections and survival in relapsed/refractory large B-cell lymphoma (R/R LBCL) patients receiving CAR T-cell therapy (CART). Although validated in its defining study, the HT score was developed in a small cohort, necessitating independent external validation. This study externally validates the HT score in a real-world population-based cohort of adults with R/R LBCL receiving CART. The HT score, based on absolute neutrophil count, hemoglobin, platelets, C-reactive protein, and ferritin, was calculated before lymphodepleting chemotherapy. Of 245 consecutive patients, 171 (70%) had a HT score ≥2 (HThigh). The initial endpoint, clinically significant neutropenia (ANC < 500/µL for ≥14 days), occurred in 21% of patients. The binary HT score was associated with clinically significant neutropenia (OR 2.94 [95%CI 1.27-6.80]; P = 0.012) with a good predictive performance (AUC = 0.73). Similar results were achieved for early and late ICAHT ≥ grade 3 (OR 2.92, [95% CI 1.19 - 7.14]; P = 0.019; OR 2.42 [95% CI 1.31 - 4.47]; P = 0.005). A trend towards an association with severe infections was observed (OR 2.02 [95%CI 0.91-4.48], P = 0.085). HThigh patients had a lower progression-free and overall survival (HRs 1.84 [95%CI 1.15-2.93]; P = 0.011, and 2.83 [95%CI 1.64-4.87]; P < 0.001, respectively). The HT score identified CART-treated R/R LBCL patients at risk for clinically significant neutropenia, poor survival outcomes, and potentially severe infections.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641844","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":"Estimation of Benefit to Bispecific Antibodies in US Patients with Lymphoma and Multiple Myeloma.","authors":"Fausto Alfredo Rios-Olais, Talal Hilal","doi":"10.1182/bloodadvances.2025016176","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016176","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648536","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 bone marrow mesenchymal stromal cells-derived IL-6 to overcome acute myeloid leukemia chemoresistance.","authors":"Diyu Hou, Danni Cai, Wei Dai, Xinai Liao, Maoqing Tan, Xiaoming Zheng, Liuhuan Wang, Jingru Liu, Jin Wang, Xiaoting Wang, Qiang Fu, Huifang Huang","doi":"10.1182/bloodadvances.2024015496","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015496","url":null,"abstract":"<p><p>In acute myeloid leukemia (AML), elevated IL-6 levels in the bone marrow (BM) are linked to poor prognosis. However, the mechanisms driving this elevation and its role in chemoresistance remain unclear. Using the Prrx1-Cre system, we selectively deleted Il6 in BM mesenchymal stromal cells (MSCs) and established an AML mouse model. Our results show that MSCs are a major source of IL-6 in AML BM. Importantly, Il6 deletion in MSCs reduced oxidative phosphorylation (OXPHOS) activity in AML cells, slowed disease progression, and enhanced the chemosensitivity to cytarabine (Ara-C). Similarly, the OXPHOS inhibitor IACS-010759 improved chemosensitivity in AML mice. Exogenous recombinant IL-6 reversed the chemosensitivity gains from Il6 deletion, confirming its role in chemoresistance. We further demonstrated that Il6 absence in MSCs inhibits mitochondria transfer to AML cells, dampening OXPHOS and enhancing Ara-C efficacy. In summary, our study underscores the critical role of Il6 from MSCs in AML progression and chemoresistance. Targeting IL-6 in MSCs may offer a promising therapeutic strategy for AML. NCT06486350.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641846","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":"Older matched sibling donor versus young haplo-identical donor for elderly patients with acute myeloid leukemia.","authors":"Xavier Poire, Myriam Labopin, Emmanuelle Polge, Didier Blaise, Patrice Chevallier, Johan A Maertens, Nicolaus Kröger, Caroline Besley, Stephanie Nguyen, Cristina Castilla-Llorente, Gérard Socié, Edouard Forcade, Anne Huynh, Igor Wolfgang Blau, Arnon Nagler, Jaime Sanz, Simona Piemontese, Mohamad Mohty, Fabio Ciceri","doi":"10.1182/bloodadvances.2024015582","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015582","url":null,"abstract":"<p><p>Selection of a suitable donor for allogeneic hematopoietic stem cell transplantation (allo-HCT) has mainly relied on human leukocyte antigen matching, and to date, a matched sibling donor (MSD) remains the first choice. However, patients with acute myeloid leukemia (AML) are older and therefore, have older siblings. Haplo-identical donors (HID) are easily available, and offspring are younger than siblings. As donor age has been associated with worse outcomes, a younger HID might be a better choice than an older MSD for older AML transplanted in first complete remission (CR1). We selected from the EBMT registry database, patients with AML, aged ≥60 years and transplanted in CR1, either from MSD aged ≥50 years or HID £ 40 years. All HID received post-transplant cyclophosphamide as graft-versus-host disease (GvHD) prophylaxis and MSD receiving in vivo T-cell depletion were included. A total of 1247 patients were identified, including 721 MSD and 526 HID. In univariate analysis, HID was associated with lower relapse incidence (p=0.01), higher non-relapse mortality (NRM) (p=0.01) and higher incidence of grade II-IV acute GvHD (p=0.01). The 2-year probability of overall survival (OS), leukemia-free survival (LFS) and GvHD-free and relapse-free survival (GRFS) were 62.5%, 56% and 47%, respectively, without any significant difference between groups. In multivariate analysis, we confirmed that HID was associated with less relapse but more NRM, which translated into similar OS, LFS and GRFS. Based on this retrospective study, young HID led to less relapse but higher NRM than older MSD after allo-HCT in an older AML population in CR1.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648538","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":"Outcomes and survival prediction in adults with sickle cell disease treated with extracorporeal membrane oxygenation.","authors":"Alison Grazioli, Michael Edward Plazak, Kate Willsey, Joseph Rabin, Raymond P Rector, Leonid Belyayev, Allison S Lankford, Thomas M Scalea, Aakash Shah, Bradley S Taylor, Mark T Gladwin","doi":"10.1182/bloodadvances.2025016368","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016368","url":null,"abstract":"<p><p>The utility of extracorporeal membrane oxygenation (ECMO) support for adult patients with sickle cell disease (SCD) remains poorly understood. We aimed to characterize a cohort of adult individuals with SCD in the Extracorporeal Life Support Organization (ELSO) registry who underwent venoarterial (VA) or venovenous (VV) ECMO treatment, assess clinical outcomes for each modality and determine predictors of mortality. This multicenter, retrospective study evaluated in-hospital mortality and clinical outcomes such as bleeding and thrombotic events (BTE) of adult VA and VV ECMO ELSO registry patients with SCD associated ICD-9/10-CM codes. Post hoc multivariable logistic regression model was developed assessing predictors of mortality. Of 206 included patients, 126 and 80 were cannulated for VA ECMO or VV ECMO, respectively. Eighty-three patients (40.3%) were discharged alive; In-hospital survival was 25.5% and 61.1% for VA and VV ECMO, respectively (p<0.001). BTE was common during VA (45.6%) and VV (33.8%) ECMO support. There was significant increase in BTE incidence for non-survivors compared to survivors with VA ECMO (55.4% vs. 26.5%, p<0.001) and VV ECMO (58.1% vs. 18.4%, p=0.01). Male sex, increased age, pre-ECLS cardiac arrest, cannulation for eCPR, and elevated lactate were predictive of in-hospital mortality in the VA ECMO cohort. In adult patients with SCD, in-hospital survival was significantly lower with VA ECMO compared to VV ECMO. Male sex, increased age, eCPR support, elevated lactate and pre-ECLS arrest were strongest indicators of VA ECMO mortality. Bleeding and thrombotic complications have an association with in-patient mortality for those treated with ECMO.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612104","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}