American Journal of Hematology最新文献

{"title":"NOTCH1 Mutations Are Associated With Therapy-Resistance in Patients With B-Cell Lymphoma Treated With CD20xCD3 Bispecific Antibodies","authors":"Emil R. Kyvsgaard, Morten Grauslund, Lene Sjø, Linea Cecilie Melchior, Trine Lønbo Grantzau, Lise Mette Rahbek Gjerdrum, Trine Trab, Lærke Sloth Andersen, Anne Ortved Gang, Marie Breinholt, Michael Boe Møller, Jacob Haaber Christensen, Thomas Stauffer Larsen, Michael Roost Clausen, Caroline H. Riley, Carsten U. Niemann, Kirsten Grønbæk, Martin Hutchings, Simon Husby","doi":"10.1002/ajh.27601","DOIUrl":"10.1002/ajh.27601","url":null,"abstract":"<p>CD20 × CD3 bispecific antibodies such as glofitamab, epcoritamab, and mosunetuzumab are novel T cell engaging antibodies which have all shown convincing results and obtained FDA and EMA approval for the treatment of relapsed/refractory diffuse large B cell lymphomas (DLBCL) or follicular lymphoma (FL) with ≥ 2 prior lines of treatment [<span>1</span>]. However, approximately 50% of patients do not achieve remission when treated with single agent CD20 × CD3 bispecific antibodies.</p><p>Subgroup analysis of pivotal phase I/II trials have identified elevated LDH > 250 U/L, high tumor burden, and refractory disease as risk factors for lack of response to bispecific antibodies for refractory/relapsed DLBCL [<span>1</span>]. Downregulated TP53 target signatures, upregulated expression of MYC target genes, truncating mutations in <i>MS4A1</i> (the gene encoding CD20), and loss of CD20 antigen have been identified as predictive factors for lack of response [<span>2-5</span>]. Previously, tumor mutations in <i>TP53</i> have been associated with poor response to both immunochemotherapy (i.e. R-CHOP) and CD19 CAR-T cell therapy in patients with B-cell lymphoma, but have not yet been examined thoroughly with long-term follow-up in patients treated with CD20 × CD3 bispecific antibodies.</p><p>In this retrospective study, we included patients from Rigshospitalet, Copenhagen, and Vejle University Hospital, both in Denmark, who received CD20 × CD3 bispecific antibodies between 2017 and 2023 as part of phase 1 or phase 2 clinical trials. The full list of regimens used are shown in Table S1. For exhaustive methods used, refer to the Supporting Information S1.</p><p>We collected pre-treatment formalin-fixed and paraffin-embedded (FFPE) archival specimens from 106 patients, of which 56 had sufficient DNA quantity and tumor involvement for clinical grade diagnostic next-generation sequencing (NGS). NGS was performed with a custom lymphoma panel designed in-house covering 59 commonly mutated genes in lymphoid malignancies.</p><p>We examined pre-treatment tumors from 56 patients with B-cell NHL, who received CD20 × CD3 bispecific antibodies between 2017 and 2023 and had sufficient tissue for NGS sequencing. The median age at first administration of CD20 × CD3 bispecific antibody was 70 years, 60.7% were male, and the median number of prior lines of therapy was three (Table S1). Median follow-up time was 24.2 months. Mutational profiling was additionally performed on 14 paired post-CD20 × CD3 bispecific antibody relapse samples.</p><p>Of all mutations found in pre-CD20 × CD3-treatment biopsies <i>NOTCH1</i> (detected in 4/56 [7%] of patients, Figure S1), along with <i>BRAF</i> and <i>EZH2,</i> had the strongest association with inferior PFS in a univariate Cox model (HR: 3.46, 95% CI 1.16–10.3, <i>p</i> = 0.026, Tables S2 and S4, Figure S8). Furthermore, pre-CD20 × CD3-treatment <i>NOTCH1</i> mutated tumors conferred significantly worse outcomes in Kaplan–Meier an","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"712-716"},"PeriodicalIF":10.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031075","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":"Exploring the Clinical Diversity of Castleman Disease and TAFRO Syndrome: A Japanese Multicenter Study on Lymph Node Distribution Patterns","authors":"Mizuna Otsuka,&nbsp;Tomohiro Koga,&nbsp;Remi Sumiyoshi,&nbsp;Shoichi Fukui,&nbsp;Yuko Kaneko,&nbsp;Takayuki Shimizu,&nbsp;Atsushi Katsube,&nbsp;Shingo Yano,&nbsp;Yasufumi Masaki,&nbsp;Makoto Ide,&nbsp;Hajime Yoshifuji,&nbsp;Masayasu Kitano,&nbsp;Yasuharu Sato,&nbsp;Naoki Sawa,&nbsp;Hiroaki Niiro,&nbsp;Naoya Nakamura,&nbsp;David C. Fajgenbaum,&nbsp;Frits van Rhee,&nbsp;Atsushi Kawakami","doi":"10.1002/ajh.27612","DOIUrl":"10.1002/ajh.27612","url":null,"abstract":"<p>Individuals diagnosed with Castleman disease (CD) and TAFRO syndrome (characterized by thrombocytopenia, anasarca, fever, bone marrow fibrosis, and organomegaly) displays a wide range of clinical symptoms, including varying patterns of lymph node enlargement, systemic inflammation, and impaired organ function. Some patients may present with both CD and TAFRO syndrome concurrently. A retrospective study conducted across multiple centers in Japan examined 321 cases to determine if the quantity and position of swollen lymph nodes could forecast the clinical progression and intensity of these conditions. Interestingly, the study revealed that patients with TAFRO syndrome exhibited lymphadenopathy across all ranges of lymph node region counts. Moreover, no specific clinical patterns were associated with the number of affected lymph node regions in CD patients, regardless of whether they also had TAFRO syndrome. These results enhance our understanding of the clinical variability in CD and TAFRO syndrome, suggesting that a comprehensive clinical evaluation, rather than relying solely on lymph node count, is crucial for effectively managing these conditions. Additional studies are required to establish reliable diagnostic markers and to predict disease severity at the time of diagnosis, ultimately improving patient outcomes.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"592-605"},"PeriodicalIF":10.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031074","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":"Combination of Biological Aging and Genetic Susceptibility Helps Identifying At-Risk Population of Venous Thromboembolism: A Prospective Cohort Study of 394 041 Participants","authors":"Zhensheng Hu,&nbsp;Jiatang Xu,&nbsp;Runnan Shen,&nbsp;Liling Lin,&nbsp;Yangfan Su,&nbsp;Chaoyu Xie,&nbsp;Guochang You,&nbsp;Yi Zhou,&nbsp;Kai Huang","doi":"10.1002/ajh.27605","DOIUrl":"10.1002/ajh.27605","url":null,"abstract":"<div>\u0000 \u0000 <p>Phenotypic age acceleration (PhenoAgeAccel) is a novel clinical aging indicator. This study was carried out to investigate the relationship between PhenoAgeAccel and the incidence of VTE, as well as to integrate PhenoAgeAccel with genetic susceptibility to improve risk stratification of VTE. The study included 394 041 individuals from the UK Biobank. Phenotypic age was calculated based on actual age and clinical biomarkers. PhenoAgeAccel presents the residual obtained from a linear regression of phenotypic age against actual age, reflecting the rate of aging. Significant associations were observed between PhenoAgeAccel and higher risk of VTE (Hazard ratio [HR] 1.37, 95% CI: 1.32–1.42), deep vein thrombosis (DVT, HR 1.35, 95% CI: 1.29–1.42), and PE (pulmonary embolism, HR 1.41, 95% CI: 1.34–1.48) in the findings. PhenoAgeAccel exhibited a significant additive interaction with genetic susceptibility. Biologically older participants with high genetic risk have a 3.83 (95% CI: 3.51–4.18) folds risk of VTE, a 3.59 (95% CI: 3.21–4.03) folds risk of DVT, and 4.39 (95% CI: 3.88–4.98) folds risk of PE, in comparison to biologically younger participants with low genetic risk. Mediation analyses indicated that PhenoAgeAccel mediated approximately 6% of the association between cancer and VTE, and about 20% of the association between obesity and VTE. Our study indicated that PhenoAgeAccel is significantly associated with higher risk of VTE, and can be combined with genetic risk to improve VTE risk stratification. Additionally, PhenoAgeAccel holds promise as a clinical biomarker for guiding targeted prevention and treatment strategies for VTE.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"575-583"},"PeriodicalIF":10.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992003","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":"CM313 Monotherapy in Patients With Relapsed/Refractory Multiple Myeloma or Marginal Zone Lymphoma: A Multicenter, Phase 1 Dose-Escalation and Dose-Expansion Trial","authors":"Huixing Zhou,&nbsp;Zhongxia Huang,&nbsp;Baijun Fang,&nbsp;Hongmei Jing,&nbsp;Zhongjun Xia,&nbsp;Yuqin Song,&nbsp;Zhen Cai,&nbsp;Gang An,&nbsp;Ling Qin,&nbsp;Li Bao,&nbsp;Xin Li,&nbsp;Yuzhang Liu,&nbsp;Yanrong Wang,&nbsp;Ling Li,&nbsp;Wenming Chen","doi":"10.1002/ajh.27573","DOIUrl":"10.1002/ajh.27573","url":null,"abstract":"&lt;p&gt;Multiple myeloma (MM) accounts for approximately one-tenth of all hematological malignancies. Although immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have significantly prolonged survival of MM patients, relapses are almost inevitable [&lt;span&gt;1&lt;/span&gt;]. Patients refractory to IMiDs and PIs have a poor prognosis, highlighting the urgency to develop new agents with target specificity in patients with relapsed/refractory MM (RRMM). CD38 is a type 2 transmembrane glycoprotein highly expressed in hematological malignancies and low in normal tissues, permitting CD38-targeting antibody a novel therapeutic option for RRMM. Currently, two anti-CD38 monoclonal antibodies, daratumumab and isatuximab, have been approved for the treatment of RRMM [&lt;span&gt;2-4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;CM313 is a novel humanized monoclonal antibody with a unique complementarity-determining region sequence that facilitates its high affinity to a spectrum of CD38-positive cells. Preclinical studies showed its comparable in vitro killing activities in target cells and anti-tumor activities with daratumumab, without obvious off-target toxicity [&lt;span&gt;5&lt;/span&gt;]. CM313 also demonstrated encouraging efficacy and favorable safety in patients with immune thrombocytopenia [&lt;span&gt;6&lt;/span&gt;]. Here, we report the first-in-human phase 1 trial of CM313 monotherapy in patients with RRMM and marginal zone lymphoma (MZL).&lt;/p&gt;&lt;p&gt;This was a multicenter, open-label phase 1 trial consisting of a dose-escalation phase and a dose-expansion phase (NCT04818372). Eligible RRMM patients had a confirmed diagnosis of MM based on the International Myeloma Working Group guidelines, measurable disease, an Eastern Cooperative Oncology Group performance-status score of ≤ 2 points, and prior treatment with IMiDs and PIs. Key exclusion criteria were primary refractory MM, diagnosis of amyloidosis, plasma-cell leukemia, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome, confirmed central nervous system metastases, and prior therapy with anti-CD38 monoclonal antibodies. Detailed eligibility criteria for RRMM and MZL patients are presented in the Supporting Information. Patients in the dose-escalation phase received 9 escalating doses of CM313 intravenously (0.006, 0.06, 0.3, 1.0, 2.0, 4.0, 8.0, 16, and 24 mg/kg) once in a 21-day observation period for dose-limiting toxicities (DLTs), then once weekly (QW) for the next 7 doses, then every 2 weeks (Q2W) for 8 doses, and then every 4 weeks (Q4W) onwards until disease progression or unacceptable toxicities. In the dose-expansion phase, CM313 was administered intravenously at doses of 4.0 and 16 mg/kg QW for 8 doses, then Q2W for 8 doses, and then Q4W thereafter until disease progression or unacceptable toxicities (Figure S1A).&lt;/p&gt;&lt;p&gt;Primary endpoints were safety and tolerability in the dose-escalation phase and overall response rate (ORR) in the dose-expansion phase. Secondary endpoints included clinical benefit r","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 3","pages":"531-534"},"PeriodicalIF":10.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27573","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992000","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":"Erdheim-Chester Disease With Significant Response of Large Vessel Disease to Cobimetinib Monotherapy","authors":"Nehaal Ahmed, Jithma P. Abeykoon, Angela Collie, Matthew J. Koster","doi":"10.1002/ajh.27606","DOIUrl":"https://doi.org/10.1002/ajh.27606","url":null,"abstract":"<h2> Conflicts of Interest</h2>\u0000<p>The authors declare no conflicts of interest.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"32 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992001","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":"Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia: Phase 2 Part B Study","authors":"Nichola Cooper,&nbsp;A. J. Gerard Jansen,&nbsp;Robert Bird,&nbsp;Jiří Mayer,&nbsp;Michelle Sholzberg,&nbsp;Michael D. Tarantino,&nbsp;Mamta Garg,&nbsp;Paula F. Ypma,&nbsp;Vickie McDonald,&nbsp;Charles Percy,&nbsp;Milan Košťál,&nbsp;Isaac Goncalves,&nbsp;Lachezar H. Bogdanov,&nbsp;Terry B. Gernsheimer,&nbsp;Remco Diab,&nbsp;Mengjie Yao,&nbsp;Ahmed Daak,&nbsp;David J. Kuter","doi":"10.1002/ajh.27539","DOIUrl":"10.1002/ajh.27539","url":null,"abstract":"<p>Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count &lt; 30 × 10⁹/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017–004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 10⁹/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 10⁹/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 10⁹/L or ≥ 30 × 10⁹/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet &gt; 80 × 10⁹/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients.</p><p>\u0000 <b>Trial Registration:</b> NCT03395210, EudraCT 2017-004012-19</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 3","pages":"439-449"},"PeriodicalIF":10.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27539","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021097","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":"Association Between Anticoagulant-Related Bleeding and Mortality in Patients With Solid Tumors and Cancer-Associated Venous Thromboembolism","authors":"Amir Mahmoud,&nbsp;Suhong Luo,&nbsp;Brian F. Gage,&nbsp;Amber Afzal,&nbsp;Kenneth Carson,&nbsp;Su-Hsin Chang,&nbsp;Martin Schoen,&nbsp;Tzu-Fei Wang,&nbsp;Kristen M. Sanfilippo","doi":"10.1002/ajh.27588","DOIUrl":"10.1002/ajh.27588","url":null,"abstract":"<p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 3","pages":"535-538"},"PeriodicalIF":10.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27588","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991281","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":"Impact of Pre-Treatment Comorbidity Burden on Survival in Patients Receiving Venetoclax Plus Hypomethylating Agents","authors":"Giovanni Marconi,&nbsp;Elisabetta Petracci,&nbsp;Giuseppe Lanzarone,&nbsp;Calogero Vetro,&nbsp;Maria Paola Martelli,&nbsp;Cristina Papayannidis,&nbsp;Ernesta Audisio,&nbsp;Paola Minetto,&nbsp;Carola Riva,&nbsp;Fabio Guolo,&nbsp;Gianluca Martini,&nbsp;Patrizia Zappasodi,&nbsp;Federico Vincenzo,&nbsp;Federica Gigli,&nbsp;Davide Griguolo,&nbsp;Michela Rondoni,&nbsp;Giulia Ciotti,&nbsp;Erika Borlenghi,&nbsp;Nadia Ciccone,&nbsp;Fanny Erika Palumbo,&nbsp;Jacopo Nanni,&nbsp;Daniele Mattei,&nbsp;Massimo Bernardi,&nbsp;Alessandro Cignetti,&nbsp;Chiara Zingaretti,&nbsp;Bernadette Vertogen,&nbsp;Claudio Cerchione,&nbsp;Francesco Lanza,&nbsp;Daniela Cilloni,&nbsp;Lorenzo Brunetti,&nbsp;Raffaele Palmieri,&nbsp;Antonio Curti,&nbsp;Maria Benedetta Giannini,&nbsp;Elisabetta Todisco,&nbsp;AVALON research group,&nbsp;Nicola Fracchiolla,&nbsp;Giovanni Martinelli","doi":"10.1002/ajh.27591","DOIUrl":"10.1002/ajh.27591","url":null,"abstract":"<p>Expectation of survival of patients receiving HMA + VEN is influenced by pre-treatment comorbidity burden.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"708-711"},"PeriodicalIF":10.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27591","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990541","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":"Therapeutic Errors Associated With Antithrombotic Medications Reported to United States Poison Centers","authors":"Emma N. Cravo,&nbsp;Hannah L. Hays,&nbsp;Jaahnavi Badeti,&nbsp;Henry A. Spiller,&nbsp;Natalie I. Rine,&nbsp;Motao Zhu,&nbsp;Gary A. Smith","doi":"10.1002/ajh.27595","DOIUrl":"10.1002/ajh.27595","url":null,"abstract":"<p>The objective of this study was to investigate the characteristics and trends of therapeutic errors in non-healthcare facility settings associated with antithrombotic medications reported to United States Poison Centers by analyzing data from the National Poison Data System from 2000 to 2021. There were 57 288 reported therapeutic error-related exposures involving antithrombotic medications as the primary substance. The rate of therapeutic errors increased by 590.9% during this 22-year period. Although most (90.1%) therapeutic errors were clinically inconsequential and did not receive treatment at a healthcare facility, 2.3% were medically admitted, and 2.1% experienced a serious medical outcome, including 16 fatalities. Three-fourths (74.9%) of therapeutic errors were among &gt; 59-year-olds, and females represented 58.0% of exposures. Warfarin was the most commonly involved antithrombotic medication (37.5%), followed by direct oral anticoagulants (DOACs, 28.7%) and clopidogrel (23.3%). Therapeutic errors involving warfarin were more likely to be associated with a medical admission (odds ratio [OR] = 2.23; 95% confidence interval [CI]: 1.99–2.49) or a serious medical outcome (OR = 2.99; 95% CI: 2.65–3.37), and DOACs were less likely to be associated with a medical admission (OR = 0.53, 95% CI: 0.46–0.61) or a serious medical outcome (OR = 0.45; 95% CI: 0.38–0.53) than therapeutic errors involving other antithrombotic medications. The rate of therapeutic errors involving warfarin significantly increased by 187.0% during 2000–2011, followed by a 57.6% significant decrease during 2011–2021. The rate of therapeutic errors involving DOACs increased significantly by 1118.2% during 2011–2021. The scenario “inadvertently took/given medication twice” accounted for 56.3% of all therapeutic errors. Increased risk reduction efforts are needed to prevent antithrombotic-related therapeutic errors.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"561-574"},"PeriodicalIF":10.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27595","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987507","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":"Clinical Validation of Optical Genome Mapping in Multiple Myeloma Without Plasma Cell Enrichment","authors":"Jung Yoon,&nbsp;Jung Ah Kwon,&nbsp;Soo-Young Yoon","doi":"10.1002/ajh.27589","DOIUrl":"10.1002/ajh.27589","url":null,"abstract":"&lt;p&gt;Cytogenetic alterations are important in risk stratification for multiple myeloma (MM). Translocations involving the immunoglobulin heavy chain (IGH), such as t(4;14), t(14;16), as well as del(17p) and gain(1q), are recognized as high-risk cytogenetic markers in staging systems [&lt;span&gt;1&lt;/span&gt;]. Fluorescence in situ hybridization (FISH) is the primary method for detecting these genetic alterations. However, cytogenetic testing in MM is challenging owing to the lower proportion of plasma cells in bone marrow (BM) aspirates, which may arise from sample variability or suboptimal sample quality. To address these challenges, clinical laboratories employ CD138+ plasma cell enrichment procedures, such as cytoplasmic immunoglobulin FISH or cell sorting using either flow cytometry or magnetic beads. Although these techniques can increase the analytical sensitivity of FISH, they also come with drawbacks, such as the need for additional steps, associated costs, the time required, and the need for larger volumes of BM samples.&lt;/p&gt;&lt;p&gt;Optical genome mapping (OGM) is an emerging cytogenetic technology that offers advantages in detecting genome-wide structural variations and copy number variants with high sensitivities in hematologic malignancies [&lt;span&gt;2&lt;/span&gt;]. In MM, OGM has revealed promising results compared with the conventional cytogenetic methods, such as karyotyping and FISH [&lt;span&gt;3, 4&lt;/span&gt;]. Moreover, with its ability to perform high-resolution, genome-wide analysis, OGM facilitates the classification and detection of genetic alterations not identified by conventional methods, including those involving the &lt;i&gt;MYC&lt;/i&gt; gene [&lt;span&gt;3, 5&lt;/span&gt;]. Compared with whole-genome sequencing, OGM may be more cost-effective while achieving higher coverage, directly improving the detection of variants with low variant allele frequencies (VAFs). With the 300× coverage, OGM is reported to be capable of detecting VAF ≥ 5%.&lt;/p&gt;&lt;p&gt;In this study, we evaluated the clinical application of OGM for detecting cytogenetic alterations, which are routinely performed using FISH. Based on promising results from a pilot study using OGM on BM aspirate samples with a plasma cell percentage &gt; 50% without CD138+ plasma cell enrichment [&lt;span&gt;3&lt;/span&gt;], we aimed to evaluate the performance of OGM in samples with varying plasma cell percentages without CD138+ plasma cell enrichment. We also aimed to identify optimal plasma cell percentages to enable routine application of OGM in clinical settings.&lt;/p&gt;&lt;p&gt;This study included 25 BM aspirate samples obtained from patients with newly diagnosed MM between January 2023 and June 2024 at the Guro Hospital, Korea University (Table S1). All patients had ≥ 10% plasma cells in BM aspirates. Samples with concurrent results of plasma cell percentages obtained using flow cytometry and FISH results were included. This study was approved by the Institutional Review Board of Korea University (2024GR0240), Guro Hospital, and conducted in accordance","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"700-703"},"PeriodicalIF":10.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27589","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987524","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}