Blood advances最新文献

{"title":"Cutaneous dysbiosis characterizes the post-allogeneic hematopoietic stem cell transplantation period.","authors":"Adela R Cardones, Akintunde Emiola, Russell P Hall, Anthony D Sung, Jennifer Zhang, Amy J Petty, Charles Puza, Lauren M Bohannon, Amy T Bush, Meagan V Lew, Elizabeth Fleming, Yingai J Jin, Krista Rowe Nichols, Vaibhav Jain, Simon G Gregory, Keith M Sullivan, Nelson J Chao, Julia Oh","doi":"10.1182/bloodadvances.2021004792","DOIUrl":"10.1182/bloodadvances.2021004792","url":null,"abstract":"<p><strong>Abstract: </strong>Gut dysbiosis is linked to mortality and the development of graft-versus-host disease after hematopoietic stem cell transplantation (HSCT), but the impact of cutaneous dysbiosis remains unexplored. We performed a pilot observational study, obtained retroauricular and forearm skin swabs from 12 adult patients before conditioning chemotherapy/radiation and at 1 week, 1 month, and 3 months after allogeneic HSCT, and performed shotgun metagenomic sequencing. The cutaneous microbiome among HSCT patients was enriched for gram-negative bacteria such as Escherichia coli and Pseudomonas, fungi, and viruses. Enrichment with bacteriophages and Polyomavirus species was observed among patients who died within 1 year. We observed longitudinal stability of the cutaneous microbiome at the 3-month time point among those who survived beyond 1 year after HSCT, although these may simply be a reflection of the overall medical status of the patients. There was no association with fungal abundance and any of the outcomes observed. The cutaneous microbiome may be a reservoir of pathobionts among allogeneic HSCT patients. Our findings suggest that cutaneous dysbiosis exists after HSCT, but the ultimate implication of this to patient outcomes remains to be seen through larger studies.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"2173-2182"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032284","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":"DNMT3A regulates murine megakaryocyte-biased hematopoietic stem cell fate decisions.","authors":"Sarah M Waldvogel, Virginia Camacho, Dandan Fan, Anna G Guzman, Alejandra Garcia-Martell, Elmira Khabusheva, Jacey Rodriguez Pridgen, Josephine De La Fuente, Rachel Rau, Ashlyn G Laidman, Maria N Barrachina, Estelle Carminita, Justin A Courson, Michael R Williamson, Joanne I Hsu, Chun-Wei Chen, Jaime Reyes, Subhashree Pradhan, Rolando E Rumbaut, Alan R Burns, Benjamin Deneen, Jianzhong Su, Kellie R Machlus, Margaret A Goodell","doi":"10.1182/bloodadvances.2024015061","DOIUrl":"10.1182/bloodadvances.2024015061","url":null,"abstract":"<p><strong>Abstract: </strong>Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to be epigenetically encoded, but few differential regulatory mechanisms have been identified. In this work, we explored the role of DNA methyltransferase 3A (DNMT3A) in the megakaryocyte-biased HSC population, which is thought to reside at the top of the hematopoietic hierarchy. We demonstrate that heterozygous loss of DNMT3A (Dnmt3a+/-) in these megakaryocyte-biased HSCs has distinct consequences compared with the rest of the HSC pool. These megakaryocyte-biased HSCs become delayed in their lymphoid-repopulating ability but can ultimately regenerate all lineages. We further demonstrate that Dnmt3a+/- mice have increased numbers of megakaryocytes in the bone marrow. Analysis of DNA methylation differences between wild-type (WT) and Dnmt3a+/- HSC subsets, megakaryocyte-erythroid progenitors, and megakaryocytes revealed that DNA methylation is eroded in the mutants in a cell type-specific fashion. Although transcriptional differences between WT and Dnmt3a+/- megakaryocyte-biased HSCs are subtle, the pattern of DNA methylation loss in this HSC subset is almost completely different from that in non-megakaryocyte-biased HSCs. Together, our findings establish the role of epigenetic regulation in the fate of megakaryocyte-biased HSCs and their downstream progeny and suggest that the outcomes of DNMT3A loss might vary depending on the identity of the HSC that acquires the mutation.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"2285-2299"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572165","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":"Single-cell dynamics of breakthrough toxicities after anakinra prophylaxis for axicabtagene ciloleucel in lymphoma.","authors":"Matthew J Frigault, Ning Yao, Trisha R Berger, Marc Wehrli, Kathleen M E Gallagher, Nora Horick, Charlotte E Graham, Caron A Jacobson, Yi-Bin Chen, Mark B Leick, Zachariah DeFilipp, Areej R El-Jawahri, P Connor Johnson, Maria Dolaher, Katelin Katsis, Austin I Kim, Jennifer Crombie, Reid W Merryman, Daniella Cook, Michael Trailor, Hana Cho, Richard Jeffrey, Rhine Shen, Simone Filosto, Jenny Nater, Gad Getz, Nicholas J Haradhvala, Marcela V Maus","doi":"10.1182/bloodadvances.2024015161","DOIUrl":"10.1182/bloodadvances.2024015161","url":null,"abstract":"<p><strong>Abstract: </strong>Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy is limited by cytokine release syndrome (CRS) and neurotoxicity (NT). We sought to use once-daily prophylactic anakinra, an interleukin-1 (IL-1) receptor antagonist, to prevent CRS/NT that would require hospitalization (grade ≥2) in patients receiving axicabtagene ciloleucel for large-cell lymphoma, with the goal of facilitating outpatient therapy and management. Our study, in line with others, demonstrates that once-daily prophylactic anakinra is insufficient to prevent the development of toxicities that would require hospitalization in most patients. As part of the initial study design, we prospectively incorporated single-cell RNA sequencing to gain insight into the molecular immune signaling associated with breakthrough CRS and NT despite anakinra prophylaxis. In patients who developed breakthrough CRS or NT, we found that interferon gamma (IFN-γ) pathways and ligand-receptor activities were significantly enriched, as were cytokine levels of IFN-γ and CXCL10 in CD14+ monocytes. This correlated with increased IFN-γ and other cytokines in the peripheral blood. In infused CAR-T products, IL-4 and IL-10 anti-inflammatory pathways were negatively associated with grade ≥2 toxicities, regardless of anakinra treatment. These data identify IFN-γ as a potential key mechanism in CAR-T-associated toxicities, which is not inhibited by anakinra but may be otherwise targetable. This trial was registered at www.ClinicalTrials.gov as #NCT04150913.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"2122-2135"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389916","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":"Phase 1 trial of durvalumab (anti-PD-L1) combined with lenalidomide in relapsed/refractory cutaneous T-cell lymphoma.","authors":"Christiane Querfeld, Joycelynne Palmer, Zhen Han, Xiwei Wu, Yate-Ching Yuan, Min-Hsuan Chen, Chingyu Su, Ni-Chun Tsai, D Lynne Smith, Samantha N Hammond, Liliana Crisan, Joo Y Song, Raju Pillai, Steven T Rosen, Jasmine Zain","doi":"10.1182/bloodadvances.2024014655","DOIUrl":"10.1182/bloodadvances.2024014655","url":null,"abstract":"<p><strong>Abstract: </strong>Selective targeting of the functionally exhausted malignant T cells in cutaneous T-cell lymphoma (CTCL) and distinct cells within the tumor microenvironment (TME) via programmed cell death 1/programmed cell death ligand 1 blockade (durvalumab) may restore an antitumor immune response. The oral immunomodulator lenalidomide, which has activity in CTCL, may enhance durvalumab immune checkpoint blockade. Our phase 1/2 clinical trial of durvalumab and lenalidomide in patients with refractory/advanced CTCL sought to assess the safety and tolerability and to identify the maximum tolerated dose and recommended phase 2 dose (RP2D) of lenalidomide plus fixed-dose durvalumab. Secondary and tertiary objectives were to investigate the efficacy and effects on the TME. Thirteen patients were evaluable for toxicities and 12 for dose decisions and response. No serious adverse events (AEs) or dose-limiting toxicities (DLTs) were observed during cycles 1 to 3 (DLT evaluation period), and dose level 3 was identified as the RP2D. The most frequent AEs were tumor flare, fatigue, neutropenia, and leukopenia. Three patients developed grade 1 or 2 autoimmune thyroiditis that resolved with treatment. Best overall and skin response rates were 58.3% (95% confidence interval (95% CI), 27.7-84.8%) and 75% (95% CI: 42.8-94.5%), respectively. The median cycles of treatment were 11, and the median duration of response was 25.5 months. The combination showed clinical activity with 7 partial responses and 4 stable disease. Potentially predictive immune signatures were downregulation of -α signaling via NF-κB, interferon gamma, and phosphoinositide 3 kinase-AKT-mammalian target of rapamycin signaling pathways in responders and upregulation of MYC targets and proinflammatory pathways in nonresponders. Profiling of immune cell compositions revealed changes in individual immune cell clusters based on treatment response. This trial was registered at www.ClinicalTrials.gov as #NCT03011814.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"2247-2260"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416681","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":"BR or R-CHOP induction with rituximab maintenance in untreated, transplant-ineligible patients with mantle cell lymphoma.","authors":"Katja Gutmair, Diego Villa, Nicholas Cunningham, Elisabeth Silkenstedt, Lisa Rimsza, Colleen Ramsower, David W Scott, Alina S Gerrie, Hanneke C Kluin-Nelemans, Martin Dreyling, Eva Hoster","doi":"10.1182/bloodadvances.2024015292","DOIUrl":"10.1182/bloodadvances.2024015292","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"2302-2306"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472296","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":"A pharmacokinetic and safety study of oral arsenic trioxide in patients with acute promyelocytic leukemia.","authors":"Farhad Ravandi, Sravanti Rangaraju, Hagop Kantarjian, Guillermo Garcia-Manero, Musa Yilmaz, Kristen Baker, Terence Hall, Joy Grabenstein, Pourab Roy, Beth A Zamboni, William C Zamboni, Erica Warlick, Michael Kelly, David A Roth, Gabriel Ghiaur","doi":"10.1182/bloodadvances.2024015453","DOIUrl":"10.1182/bloodadvances.2024015453","url":null,"abstract":"<p><strong>Abstract: </strong>SY-2101 is a novel oral formulation of arsenic trioxide (ATO). Although IV ATO in combination with all trans retinoic acid is highly efficacious in treating acute promyelocytic leukemia (APL), there remains a significant unmet need due to the treatment burden associated with receiving daily ATO infusions for nearly a year and the risk of complications associated with indwelling central catheters. The pharmacokinetics (PK), safety, and tolerability of SY-2101 and ATO IV after single- and multiple-dose administration and the impact of food on PK for SY-2101 were evaluated in this phase 1 study in 15 participants with APL. SY-2101 in the fasted state demonstrated comparable systemic exposure to ATO IV based on the active metabolite arsenious acid [As(III)], with geometric mean ratios (GMRs) of SY-2101 to ATO IV of 1.00 for area under the plasma concentration (AUC) from 0 hour to last time point (AUC0-last) and from 0 hour to infinity (AUC0-inf). The GMR of SY-2101 to ATO IV maximum concentration (Cmax) was 0.76, as was expected due to the different routes of administration. Comparisons of SY-2101 in fed to fasted states demonstrated similar exposure with GMRs of AUC0-last, AUC0-inf, and Cmax at 1.08, 1.12, and 0.85, respectively, allowing for SY-2101 administration with or without food. SY-2101 was well tolerated. Most adverse events were of low grade. This study provides the first intrapatient PK crossover results directly comparing SY-2101 with ATO IV and supports the likelihood of clinical equivalence between the 2 formulations. This trial was registered at www.ClinicalTrials.gov as #NCT04996030.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"2136-2143"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527866","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":"Factors associated with early quality-of-life response to palliative care during hematopoietic cell transplantation.","authors":"Richard Newcomb, Hermioni L Amonoo, Alison R Kavanaugh, Kristin C Wharton, Michaela Rowland, James Fausto, Jason Webb, Vicki Jackson, Joseph A Greer, Jennifer S Temel, Porsha Lark, Dustin J Rabideau, Karen O'Brien, Thomas W LeBlanc, Stephanie J Lee, Areej El-Jawahri","doi":"10.1182/bloodadvances.2024014574","DOIUrl":"10.1182/bloodadvances.2024014574","url":null,"abstract":"<p><strong>Abstract: </strong>Limited data exist on factors associated with early quality-of-life (QOL) response to palliative care (PC) in patients undergoing hematopoietic cell transplantation (HCT). We conducted a secondary analysis from 2 randomized clinical trials of PC vs usual care in adults with hematologic malignancies undergoing HCT. We measured patient-reported QOL, physical and psychological symptoms, and coping (categorized as approach-oriented and avoidant) at the time of HCT admission and 2 weeks, 3 months, and 6 months after HCT. PC clinicians completed weekly surveys documenting PC domains addressed. We defined early QOL response to PC as the change in Functional Assessment of Cancer Therapy-Bone Marrow Transplant total score from HCT admission to week 2, using the median split to define \"high\" responders. A total of 252 participants were included in analyses. The median change in QOL from HCT admission to week 2 was -10.7 (range, -77.0 to +52.0). Minoritized race (odds ratio [OR], 3.2; P < .001), lower baseline QOL (OR, 0.97; P < .001), and higher physical (OR, 1.02; P = .004) and posttraumatic stress disorder symptoms (OR, 1.04; P = .008) were associated with being a high PC responder. High PC responders reported greater use of approach-oriented coping at week 2 (Δ = 2.5; P = .002) and 3 months (Δ = 1.7; P = .04) and 6 months after HCT (Δ = 2.6; P = .003). Based on PC clinician surveys during HCT, high responders' PC visits focused on coping, illness/HCT education, and symptom education, whereas low responders' visits focused on symptom management. These findings provide insights into factors associated with early QOL response to PC in HCT and help identify those most likely to benefit in real-world practice. These trials were registered at www.ClinicalTrials.gov as #NCT02207322 and #NCT03641378.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"2033-2043"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254798","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":"Treatment holidays in patients with Erdheim-Chester disease receiving vemurafenib: a prospective pilot study.","authors":"Francesco Pegoraro, Francesco Catamerò, Federica Allegretta, Giulia Palazzini, Francesco Peyronel, Eli L Diamond, Augusto Vaglio","doi":"10.1182/bloodadvances.2024015399","DOIUrl":"10.1182/bloodadvances.2024015399","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"2119-2121"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944980","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":"Finding the right fit: assessment of fitness in AML.","authors":"Nicholas Chornenki, Lee Mozessohn","doi":"10.1182/bloodadvances.2025016114","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016114","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 9","pages":"2300-2301"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980741","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":"Paudel BB, Tan S-F, Fox TE, et al. Acute myeloid leukemia stratifies as 2 clinically relevant sphingolipidomic subtypes. Blood Adv. 2024;8(5):1137-1142.","authors":"","doi":"10.1182/bloodadvances.2025016279","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016279","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 9","pages":"2231"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980769","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}