American Journal of Hematology最新文献

{"title":"MDS/MPN With SF3B1 Mutation and Thrombocytosis but Without Ring Sideroblasts","authors":"Biswadip Hazarika, Barbara J. Bain","doi":"10.1002/ajh.70040","DOIUrl":"https://doi.org/10.1002/ajh.70040","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"27 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899305","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":"Partial Nuclear Extrusion in Chronic Lymphocytic Leukemia Observed to Be an In Vitro Artefact","authors":"Rima Chatila, Guillaume Beziat, Laure Pirovano, Clément Bouyssie, Jean‐Baptiste Rieu, Barbara J. Bain","doi":"10.1002/ajh.70041","DOIUrl":"https://doi.org/10.1002/ajh.70041","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"17 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899170","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 Evolution and Recent Advances in Diagnostic Criteria for Idiopathic Multicentric Castleman Disease","authors":"FNU Alnoor, Nicholas C. Spies, Jyoti Kumar, Peyman Samghabadi, Oscar Silva, Matt X. Luo, Karen M. Chisholm, Jingjing Zhang, Alexandra Rangel, David Ng, Peng Li, Robert S. Ohgami","doi":"10.1002/ajh.70039","DOIUrl":"https://doi.org/10.1002/ajh.70039","url":null,"abstract":"Idiopathic multicentric Castleman disease (iMCD) is a rare cytokine‐driven disorder characterized by systemic inflammation, organ dysfunction, and altered lymph node microscopic architecture. Over the past decade, diagnostic criteria have evolved significantly, integrating clinical, histopathological, and molecular biomarker advancements. Key drivers of iMCD pathogenesis, such as interleukin‐6 dysregulation and other dysfunctional cytokine signaling, have been identified and led to the development of targeted therapies like siltuximab and tocilizumab. Histopathologic refinements have highlighted distinct subtypes, such as hypervascular, plasmacytic, and mixed histologic patterns, while molecular discoveries have unveiled potential paraneoplastic and clonal processes. Emerging technologies, including single‐cell sequencing, spatial transcriptomics, and digital pathology, offer promise in refining diagnostic precision and advancing personalized medicine. This review synthesizes historical frameworks, recent breakthroughs, and future directions in iMCD diagnostics, emphasizing the importance of multidisciplinary approaches for improved patient outcomes.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"22 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899093","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":"Outpatient Brexucabtagene Autoleucel in B-Cell Acute Lymphoblastic Leukemia and Mantle Cell Lymphoma","authors":"Tamer Othman, John H. Baird, Yan Wang, Stacy Pak, Hannah Zhong, Ibrahim Aldoss, Ji-Lian Cai, Alexey Danilov, Tycel J. Phillips, Vaibhav Agrawal, Karamjeet S. Sandhu, Matthew Mei, Paul B. Koller, Joycelynne Palmer, Stephen J. Forman, Lihua E. Budde, Ahmed Aribi","doi":"10.1002/ajh.70038","DOIUrl":"10.1002/ajh.70038","url":null,"abstract":"<p>Brexucabtagene autoleucel (brexu-cel) is an effective therapeutic option for relapsed/refractory (R/R) mantle cell lymphoma (MCL) and B-cell acute lymphoblastic leukemia (ALL) based on the results of the ZUMA-2 and ZUMA-3 trials, respectively [<span>1, 2</span>]. Several reports describe the feasibility of outpatient administration of chimeric antigen receptor (CAR)-T cell therapy [<span>3</span>]. However, there is limited data supporting outpatient administration of brexu-cel [<span>4, 5</span>], a CAR product associated with higher reported rates of toxicity compared to others in clinical trials [<span>2</span>]. Here, we report our experience with outpatient administration of brexu-cel infusion as compared to inpatient.</p><p>We conducted a retrospective study of adults who received commercial brexu-cel for B-ALL and MCL at City of Hope (COH) during November 1, 2020–March 31, 2024. The study was approved by the COH institutional review board (#23837). Prior to implementing our COH outpatient-CAR program in July 2022, all patients received CAR-T infusion as inpatient. Since July 2022, patients received CAR-T as outpatient but could still receive it as inpatient based on the treating physician's discretion. Tables S1–S3 describe outpatient procedures for brexu-cel selection and administration. In this study, patients were divided into two groups, the inpatient group and the outpatient group, based on their initial brexu-cel infusion setting assignment. To improve the comparability between groups, we applied propensity score (PS) nearest matching method (ratio = 1, caliper = 0.1) with ECOG performance status, Severe4 comorbidity index [<span>6</span>], and disease burden as the matching variables. These were selected because of their relationship with the tendency of receiving CAR-T inpatient and worse post-infusion prognosis based on clinical experience. The presence of severe comorbidities was defined as a Severe4 score ≥ 1 [<span>6</span>]. Disease burden was categorized as bulky for bone marrow blasts ≥ 5% and/or the presence of extramedullary or CNS disease for B-ALL or intermediate/high MIPIb for MCL at the time of LD. Outcome analyses were performed on the post-matching cohort. The primary endpoint was cumulative incidence of 100-day non-relapse mortality (NRM). Secondary endpoints included best complete response (CR) rate, overall survival (OS), progression-free survival (PFS), incidence of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), incidence and timing of inpatient admission in the outpatient group, grade ≥ 3 infections within the first 100 days, grade ≥ 3 cytopenias, and hospital resource utilization (HRU). More statistical method details are described in Table S4.</p><p>Sixty-six patients received brexu-cel, including 35 inpatient and 31 outpatient per the initial treatment setting assignment. After PS matching, the final sample included in the outcome analyses consisted of 52 p","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 10","pages":"1916-1919"},"PeriodicalIF":9.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899169","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":"Promise, Pitfalls, and Precision: Standardizing Clinical Framework for Hereditary Hemorrhagic Telangiectasia and a Call for Cost-Conscious Innovation","authors":"Magdalena Lewandowska","doi":"10.1002/ajh.70036","DOIUrl":"10.1002/ajh.70036","url":null,"abstract":"<p>Despite its prevalence as the second most common inherited bleeding disorder affecting 1 in 5000 individuals, research and therapeutic development in Hereditary hemorrhagic telangiectasia (HHT) has historically lagged in momentum as compared with hemophilia. The recent decade has ushered in a new era of treatment, including repurposing of existing anti-VEGF agents and development of HHT-specific therapeutics [<span>1</span>]. The economic burden of HHT has not been well described. The pivotal study by Dr. Al-Samkari et al. [<span>2</span>] published in this issue of the <i>American Journal of Hematology</i> provides a comprehensive analysis of healthcare resource utilization and direct medical costs associated with HHT.</p><p>The cornerstone of HHT management over the past decade has evolved from procedural interventions alone to the emergence of disease-modifying medical therapies. With randomized controlled trials evaluating antifibrinolytics, antiangiogenic agents, and other novel therapeutics, there is growing urgency for harmonized outcome measures. The consensus report by Dr. Al-Samkari and colleagues offers a robust framework to support future clinical trials, cohort studies, and regulatory submissions [<span>3</span>].</p><p>HHT has long been underrepresented in health economics literature. The study by Dr. Al-Samkari and colleagues provides a comprehensive analysis of United States health insurance claims data (Medicare, Medicaid, and commercial insurance), representing 92% of the population [<span>2</span>]. The study's findings are striking, demonstrating that HHT surpasses direct medical costs associated with sickle cell disease by ~20%, with a mean per-patient-per year (PPPY) cost of $19 386 compared with $16 538. For patients who are anemic and have HHT, that PPPY cost escalates to $27 147, rivaling that of muscular dystrophy. Most notably, patients requiring hematologic support, such as intravenous iron or red blood cell transfusion, incur costs nearing $40 298 annually.</p><p>The authors discuss the growing use of systemic pharmacologic interventions, including antiangiogenic (bevacizumab and pazopanib) [<span>4, 5</span>] and immunomodulatory (pomalidomide) [<span>6</span>] agents for management of HHT-related epistaxis and gastrointestinal bleeding. This therapy, albeit costly, are promising in efficacy in reducing bleeding and anemia.</p><p>The greatest limitation of the study is that the claims data are collected for patients with confirmed HHT, excluding individuals who have not yet been diagnosed. Unfortunately, diagnostic delay is not uncommon in HHT. As this was a claims-based analysis, there is absence of detailed clinical outcome data to correlate with treatment efficacy.</p><p>The sobering reality is that bleeding and its sequelae is the primary cost driver in HHT, and it is indeed very expensive.</p><p>This study serves as a clarion call for clinicians, researchers, and policymakers. HHT is a high-cost, high-need co","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 10","pages":"1719-1721"},"PeriodicalIF":9.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851257","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":"Known Prognostic Models Fail to Predict Outcomes for Venetoclax and Azacitidine in Relapsed/Refractory Acute Myeloid Leukemia: A Single-Center Retrospective Analysis.","authors":"Jason S Gilbert,Megan Connor,Grace Bosma,Jingjing Zhang,Christine M McMahon,Maria L Amaya,Jonathan Gutman,Marc Schwartz,Andrew Kent,Diana Abbott,Daniel A Pollyea","doi":"10.1002/ajh.70034","DOIUrl":"https://doi.org/10.1002/ajh.70034","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"12 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850870","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":"Double Bite Cells in Oxidative Hemolytic Anemia.","authors":"Jacob R Anderson,Marie A Hollenhorst","doi":"10.1002/ajh.70035","DOIUrl":"https://doi.org/10.1002/ajh.70035","url":null,"abstract":"Double bite cells on a peripheral blood smear help to establish the diagnosis of oxidant hemolysis due to recreational alkyl nitrite use in a man with normal G6PD.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"21 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825455","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":"CD19 CAR T-Cell Therapy for Primary Mediastinal Large B-Cell Lymphoma: A CIBMTR Analysis","authors":"Jordan Gauthier,&nbsp;Kwang W. Ahn,&nbsp;Jinalben Patel,&nbsp;Qinghua Lian,&nbsp;Sherif Badawy,&nbsp;Mitchell S. Cairo,&nbsp;Julio Delgado,&nbsp;Natalie Grover,&nbsp;Bradley Haverkos,&nbsp;Marcos de Lima,&nbsp;Adriana Malone,&nbsp;Alberto Mussetti,&nbsp;Yago Nieto,&nbsp;Attaphol Pawarode,&nbsp;Laurie Pearson,&nbsp;Melhem Solh,&nbsp;Anna Sureda,&nbsp;Aung M. Tun,&nbsp;Kitsada Wudhikarn,&nbsp;Samuel Yamshon,&nbsp;Mazyar Shadman,&nbsp;Cameron J. Turtle,&nbsp;Mehdi Hamadani,&nbsp;Alex F. Herrera","doi":"10.1002/ajh.70033","DOIUrl":"10.1002/ajh.70033","url":null,"abstract":"<div>\u0000 \u0000 <p>T cells engineered with CD19-directed chimeric antigen receptors (CD19 CAR) T cells have become standard treatment for patients with high risk, relapsed or refractory (R/R) large B-cell lymphomas (LBCL). However, outcomes in patients with rare subsets of LBCL, such as primary mediastinal large B-cell lymphoma (PBMCL), have not been well characterized. The impact of prior immune checkpoint inhibitor (ICI) treatment, commonly used to treat R/R PMBCL, is also unknown. To address these gaps, we retrospectively analyzed CIBMTR registry data including PMBCL patients undergoing CD19 CAR T-cell therapy per standard-of-care. A total of 135 PMBCL adults from 66 centers were included. Median age at the time of CAR T-cell therapy was 32. Thirty-nine patients (28.9%) had received an ICI prior to CAR T-cell therapy. The best overall and complete response (CR) rates after CD19 CAR T-cell therapy were 79% and 67.7%, respectively. The 2-year progression-free (PFS) and overall survival (OS) were 58.6% (95% CI, 49.7–67.3) and 80.8% (95% CI, 72.6–87.8), respectively. The 2-year cumulative incidence (CI) of relapse and non-relapse mortality (NRM) were 36% (95% CI, 27.8–44.7) and 5.4% (95% CI, 1.9–10.5), respectively. We observed grade ≥ 3 CRS and ICANS in 6.1% and 14.7%, respectively. Prior ICI exposure was associated with lower 2-year CI of relapse (ICI-exposed, 21.7%; ICI-naïve, 41.6%; <i>p</i> = 0.03) and higher 2-year NRM (ICI-exposed, 11.7%; ICI-naïve, 2.8%; <i>p</i> = 0.03). We could not confirm statistically different PFS (<i>p</i> = 0.19) or OS (<i>p</i> = 0.26) between ICI-exposed and ICI-naïve patients. CD19 CAR T-cell therapy led to high rates of durable responses in PMBCL patients with low rates of severe toxicities.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 10","pages":"1792-1802"},"PeriodicalIF":9.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812958","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":"Association of Pre-Diagnostic Clonal Hematopoiesis of Indeterminate Potential With Prognosis Among Patients With Cancer.","authors":"Xinyuan Liu,Hans-Olov Adami,Tove Wästerlid,Huiwen Xue,Maria Feychting,Karin E Smedby,Fang Fang,Qianwei Liu","doi":"10.1002/ajh.70028","DOIUrl":"https://doi.org/10.1002/ajh.70028","url":null,"abstract":"Clonal hematopoiesis of indeterminate potential (CHIP) might impair prognosis of several cancer types. Since previous studies predominantly focused on CHIP after cancer diagnosis, little is known about whether CHIP prior to cancer diagnosis predicts outcome. We performed a prospective cohort study, including 63 486 patients with cancer during 2006 to 2022 in the UK Biobank, to evaluate the association between pre-diagnostic CHIP and survival of cancer patients. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models. We identified 2860 patients with cancer and pre-diagnostic CHIP, and 60 626 cancer patients without CHIP. During a median follow-up of 4.2 years, 1162 patients died in the CHIP group (921 cancer-specific deaths), and 17 825 in the reference group (14 785 cancer-specific deaths). Cancer patients with pre-diagnostic CHIP exhibited a higher rate of overall death (HR 1.18, 95% CI: 1.11-1.25) and cancer-specific death (HR 1.17, 95% CI: 1.09-1.25) compared with the reference group. A significant association of both overall death and cancer-specific death was observed for myeloproliferative neoplasms, multiple myeloma, breast cancer, non-Hodgkin lymphoma, and acute myeloid leukemia/myelodysplastic syndromes. The increased rate of both overall death and cancer-specific death was noted for CHIP with TET2, SRSF2, or JAK2 mutation. These findings suggested extended clinical awareness in cancer patients with pre-diagnostic CHIP.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"12 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812957","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":"Characterization of Breakthrough Hemolysis in Patients With Paroxysmal Nocturnal Hemoglobinuria: An International Multicenter Experience.","authors":"Bruno Fattizzo,Giacinto Luca Pedone,Elisabetta Metafuni,Eloise Beggiato,Valentina Giai,Esther Natalie Oliva,Antony Ricchiuti,Marta Bortolotti,Simona Raso,Daniela Carlino,Mara Memoli,Sofia Vecchi,Jennifer Vidler,Sukanya Gogoi,Shreya Goel,Anna Corby,Roochi Trikha,Sneha Balakrishnan,Francesco Passamonti,Anna Paola Iori,Simona Sica,Shreyans Gandhi,Wilma Barcellini,Austin Kulasekararaj","doi":"10.1002/ajh.70032","DOIUrl":"https://doi.org/10.1002/ajh.70032","url":null,"abstract":"Breakthrough hemolysis (BTH) is defined as a hemolytic exacerbation in a patient with paroxysmal nocturnal hemoglobinuria (PNH) treated with complement inhibitors (CIs). In the current era of several terminal and proximal inhibitors, there are no guidelines for defining BTH and its severity, and clinical management is not standardized. This retrospective, observational, and multicentric study evaluated BTH frequency and severity in PNH patients treated with complement inhibitors from 2007 until February 2025 at 10 centers across Italy (9 centers) and the United Kingdom (1 center). A total of 271 BTH events occurred in 102 out of 198 patients (51%), with 36/198 (18%) patients experiencing 3 or more BTH episodes over the 18-year follow-up. Most events (55%) were prompted by infections, and 24 (10%) were linked to poor compliance with oral alternative pathway inhibitors. BTH was clinically severe in about half of patients, requiring transfusion in 46%, CI dosing adjustment in 17%, and anticoagulant prophylaxis in 16%. Overall, 5 (2%) breakthrough thrombotic events occurred in patients not on prophylaxis, all during an infection. BTH incidence was 0.19 events per patient-year, maximal with proximal inhibitors (0.4 events per patient-year), and lower for anti-C5 (0.18 per patient-year). By logistic regression analysis, the main predictors of BTH were more severe disease at diagnosis (increased LDH and a shorter time to first complement inhibitor), treatment with proximal inhibitors, and poorer EBMT response category.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"11 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812959","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}