Tzu-Fei Wang, Erik Yeo, Peter L. Gross, Chantal Séguin, Cynthia Wu, Sudeep Shivakumar, Ranjeeta Mallick, Aurélien Delluc, Julien D'Astous, Miriam Kimpton, Guillaume Roberge, Deborah M. Siegal, Tobias Tritschler, Grégoire Le Gal, Marc Carrier
Patients with cancer-associated thrombosis (CAT) are commonly treated with low-molecular-weight heparin (LMWH), but whether dose capping is needed in patients over 90 kg is unclear. We conducted the WAVe study, a multicenter prospective cohort study in adult patients (≥ 18 years) with acute CAT and a weight of over 90 kg starting anticoagulation. Patients received weight-adjusted dalteparin at 200 IU/kg per day (up to 33 000 IU) for 30 (± 4) days, after which anticoagulation was continued per clinician discretion and followed for 6 months. The primary outcome was major bleeding (MB) at 30 days. Secondary outcomes included objectively confirmed recurrent venous thromboembolism (VTE) at 30 days and trough anti-Xa levels. The cumulative incidences of outcomes were estimated by time-to-event analysis, with death as a competing risk. The study stopped early due to recruitment challenges after 91 patients. Median weight and daily dose of dalteparin were 107.5 kg and 22 500 IU, respectively. Three patients had a MB episode for a cumulative incidence of 5.3% (95% CI 1.1%–14.8%) at 30 days. One patient had recurrent VTE for a cumulative incidence of 1.2% (95% CI 0.1%–5.7%) at 30 days. No significant bioaccumulation noted up to Day 30 based on trough anti-Xa levels. The median Day 7 trough anti-Xa levels were higher in those with bleeding events within 30 days compared to those without (0.6 vs. 0.2 IU/mL, p = 0.01). Our results suggest that weight-adjusted dosing of dalteparin in patients over 90 kg is associated with acceptable rates of bleeding and thrombosis.
Trial Registration: NCT03297359
癌症相关性血栓（CAT）患者通常使用低分子肝素（LMWH）治疗，但对于体重超过90公斤的患者是否需要剂量上限尚不清楚。我们进行了WAVe研究，这是一项多中心前瞻性队列研究，研究对象是患有急性CAT且体重超过90kg开始抗凝治疗的成年患者（≥18岁）。患者接受体重调整后的达特帕林治疗，剂量为每天200 IU/kg（最高33,000 IU），持续30（±4）天，之后根据临床医生的判断继续抗凝治疗，随访6个月。主要结局为30天大出血（MB）。次要结果包括客观确认的30天静脉血栓栓塞复发（VTE）和抗xa水平谷底。结果的累积发生率通过事件时间分析估计，死亡是一个竞争风险。由于91名患者的招募挑战，该研究提前停止。dalteparin的中位体重和日剂量分别为107.5 kg和22 500 IU。3例患者在30天发生MB发作，累计发生率为5.3% （95% CI 1.1%-14.8%）。1例患者30天静脉血栓栓塞复发，累计发生率为1.2% （95% CI 0.1%-5.7%）。根据抗xa谷底水平，在第30天没有发现显著的生物积累。30天内有出血事件的患者第7天抗xa水平中位数高于无出血事件的患者（0.6 vs. 0.2 IU/mL, p = 0.01）。我们的研究结果表明，体重超过90公斤的患者的体重调整剂量与可接受的出血和血栓发生率相关。试验注册：NCT03297359。
{"title":"A Multicenter Prospective Cohort Study on the Use of Weight-Adjusted Dalteparin in Patients Over 90 kg With Acute Cancer-Associated Venous Thromboembolism—The WAVe Study","authors":"Tzu-Fei Wang, Erik Yeo, Peter L. Gross, Chantal Séguin, Cynthia Wu, Sudeep Shivakumar, Ranjeeta Mallick, Aurélien Delluc, Julien D'Astous, Miriam Kimpton, Guillaume Roberge, Deborah M. Siegal, Tobias Tritschler, Grégoire Le Gal, Marc Carrier","doi":"10.1002/ajh.70127","DOIUrl":"10.1002/ajh.70127","url":null,"abstract":"<p>Patients with cancer-associated thrombosis (CAT) are commonly treated with low-molecular-weight heparin (LMWH), but whether dose capping is needed in patients over 90 kg is unclear. We conducted the WAVe study, a multicenter prospective cohort study in adult patients (≥ 18 years) with acute CAT and a weight of over 90 kg starting anticoagulation. Patients received weight-adjusted dalteparin at 200 IU/kg per day (up to 33 000 IU) for 30 (± 4) days, after which anticoagulation was continued per clinician discretion and followed for 6 months. The primary outcome was major bleeding (MB) at 30 days. Secondary outcomes included objectively confirmed recurrent venous thromboembolism (VTE) at 30 days and trough anti-Xa levels. The cumulative incidences of outcomes were estimated by time-to-event analysis, with death as a competing risk. The study stopped early due to recruitment challenges after 91 patients. Median weight and daily dose of dalteparin were 107.5 kg and 22 500 IU, respectively. Three patients had a MB episode for a cumulative incidence of 5.3% (95% CI 1.1%–14.8%) at 30 days. One patient had recurrent VTE for a cumulative incidence of 1.2% (95% CI 0.1%–5.7%) at 30 days. No significant bioaccumulation noted up to Day 30 based on trough anti-Xa levels. The median Day 7 trough anti-Xa levels were higher in those with bleeding events within 30 days compared to those without (0.6 vs. 0.2 IU/mL, <i>p</i> = 0.01). Our results suggest that weight-adjusted dosing of dalteparin in patients over 90 kg is associated with acceptable rates of bleeding and thrombosis.</p><p>\u0000 <b>Trial Registration:</b> NCT03297359</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 1","pages":"79-88"},"PeriodicalIF":9.9,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477557","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}
Francesco Pegoraro, Francesco Peyronel, Matthias Papo, Riccardo Sutera, Francesco Catamerò, Francesco Poeta, Jerome Razanamahery, Emmanuel Ledoult, Tanguy Le Scornet, Mathilde de Menthon, Etienne Riviere, Elena Sieni, Stephane Barete, Ahmed Idbaih, Fleur Cohen-Aubart, Zahir Amoura, Jean-François Emile, Augusto Vaglio, Julien Haroche
<p>Erdheim-Chester disease (ECD) is a rare myeloid neoplasm driven by somatic mutations in genes of the MAPK pathway [<span>1</span>]. The <i>BRAF</i> <sup> <i>V600E</i> </sup> mutation is found in ~60% of ECD patients and can be targeted by specific inhibitors (BRAFi), such as vemurafenib, dabrafenib, and encorafenib [<span>1</span>]. The introduction in 2013 of BRAFi—and more recently of MEK inhibitors (MEKi)—revolutionized the management of patients with ECD [<span>2-4</span>]. These treatments induce rapid and sustained responses, but relapses occur in most cases upon discontinuation, which is usually prompted by their toxicity [<span>2</span>].</p><p>In a recent report on 64 ECD patients treated with BRAFi, discontinuations were very frequent (61%) and mostly induced by adverse events, with poor health-related quality of life and high symptom burden [<span>5</span>]. In contrast, our routine clinical experience suggests a more favorable tolerability profile, with fewer discontinuations and generally manageable toxicities. We herein investigated the real-life efficacy and tolerability of BRAFi monotherapy in a large cohort of patients with ECD.</p><p>Patients were diagnosed according to the latest consensus guidelines on ECD [<span>6</span>], and followed in France (Pitié-Salpêtrière Hospital, Paris; Dijon University Hospital, Dijon; Lille University Hospital, Lille; Nantes University Hospital, Nantes; Bicêtre Hospital, Le Kremlin Bicêtre; Haut-Lévèque University Hospital, Bordeaux) and Italy (Meyer Children's Hospital IRCCS, Florence).</p><p>We assessed response to treatment, tolerability (according to the CTCAE criteria) [<span>7</span>], and potential predictors of response. Response was defined as a composite endpoint including clinical, radiologic, and metabolic features, as previously described [<span>8-10</span>]. The event-free survival was defined as the time to treatment discontinuation due to progression or toxicity, or death, and was estimated using a Kaplan–Meier survival analysis. Dose modifications were not considered events. Predictors of response to BRAFi were investigated through univariable and multivariable logistic regression models. A two-sided <i>p</i> value ≤ 0.05 was considered to indicate statistical significance. The study was approved by the Ethics committee of the Ile de France III (#2011-A00447-34) and the Institutional Review Board of the Meyer Children's Hospital IRCCS (#139/2020) and was conducted in accordance with the Declaration of Helsinki and its later amendments [<span>11</span>].</p><p>We identified 172 patients with ECD, all harboring the <i>BRAF</i> <sup> <i>V600E</i> </sup> mutation, who received BRAFi monotherapy since 2012 (Figure 1A). The clinical presentation is detailed in Table 1. Their median age at ECD diagnosis was 59 years (IQR 49–69), and 119 were men (69%). A hundred and twenty-nine patients (75%) had mult
{"title":"Real-Life Efficacy and Safety of BRAF Inhibitors in Erdheim-Chester Disease","authors":"Francesco Pegoraro, Francesco Peyronel, Matthias Papo, Riccardo Sutera, Francesco Catamerò, Francesco Poeta, Jerome Razanamahery, Emmanuel Ledoult, Tanguy Le Scornet, Mathilde de Menthon, Etienne Riviere, Elena Sieni, Stephane Barete, Ahmed Idbaih, Fleur Cohen-Aubart, Zahir Amoura, Jean-François Emile, Augusto Vaglio, Julien Haroche","doi":"10.1002/ajh.70137","DOIUrl":"10.1002/ajh.70137","url":null,"abstract":"<p>Erdheim-Chester disease (ECD) is a rare myeloid neoplasm driven by somatic mutations in genes of the MAPK pathway [<span>1</span>]. The <i>BRAF</i>\u0000 <sup>\u0000 <i>V600E</i>\u0000 </sup> mutation is found in ~60% of ECD patients and can be targeted by specific inhibitors (BRAFi), such as vemurafenib, dabrafenib, and encorafenib [<span>1</span>]. The introduction in 2013 of BRAFi—and more recently of MEK inhibitors (MEKi)—revolutionized the management of patients with ECD [<span>2-4</span>]. These treatments induce rapid and sustained responses, but relapses occur in most cases upon discontinuation, which is usually prompted by their toxicity [<span>2</span>].</p><p>In a recent report on 64 ECD patients treated with BRAFi, discontinuations were very frequent (61%) and mostly induced by adverse events, with poor health-related quality of life and high symptom burden [<span>5</span>]. In contrast, our routine clinical experience suggests a more favorable tolerability profile, with fewer discontinuations and generally manageable toxicities. We herein investigated the real-life efficacy and tolerability of BRAFi monotherapy in a large cohort of patients with ECD.</p><p>Patients were diagnosed according to the latest consensus guidelines on ECD [<span>6</span>], and followed in France (Pitié-Salpêtrière Hospital, Paris; Dijon University Hospital, Dijon; Lille University Hospital, Lille; Nantes University Hospital, Nantes; Bicêtre Hospital, Le Kremlin Bicêtre; Haut-Lévèque University Hospital, Bordeaux) and Italy (Meyer Children's Hospital IRCCS, Florence).</p><p>We assessed response to treatment, tolerability (according to the CTCAE criteria) [<span>7</span>], and potential predictors of response. Response was defined as a composite endpoint including clinical, radiologic, and metabolic features, as previously described [<span>8-10</span>]. The event-free survival was defined as the time to treatment discontinuation due to progression or toxicity, or death, and was estimated using a Kaplan–Meier survival analysis. Dose modifications were not considered events. Predictors of response to BRAFi were investigated through univariable and multivariable logistic regression models. A two-sided <i>p</i> value ≤ 0.05 was considered to indicate statistical significance. The study was approved by the Ethics committee of the Ile de France III (#2011-A00447-34) and the Institutional Review Board of the Meyer Children's Hospital IRCCS (#139/2020) and was conducted in accordance with the Declaration of Helsinki and its later amendments [<span>11</span>].</p><p>We identified 172 patients with ECD, all harboring the <i>BRAF</i>\u0000 <sup>\u0000 <i>V600E</i>\u0000 </sup> mutation, who received BRAFi monotherapy since 2012 (Figure 1A). The clinical presentation is detailed in Table 1. Their median age at ECD diagnosis was 59 years (IQR 49–69), and 119 were men (69%). A hundred and twenty-nine patients (75%) had mult","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 1","pages":"182-186"},"PeriodicalIF":9.9,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461314","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}
Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable clinical efficacy in treating hematological malignancies. Nevertheless, the limited persistence of CAR-T cells in vivo remains a major therapeutic hurdle, leading to disease relapse. This review examines current strategies to enhance CAR-T cell durability, focusing on recent advances in CAR structural design, gene editing techniques, ex vivo culture optimization, clinical management approaches, and in vivo preparation. By integrating insights from preclinical studies and clinical trials, we provide a comprehensive analysis of methods to prolong CAR-T cell persistence from a technical perspective and discuss future directions.
{"title":"Strategies to Enhance CAR-T Cell Persistence in Hematologic Malignancies: From Molecular Design to Clinical Optimization","authors":"Mengqi Yu, Tingting Yang, Shuyi Ding, Yongxian Hu","doi":"10.1002/ajh.70131","DOIUrl":"10.1002/ajh.70131","url":null,"abstract":"<div>\u0000 \u0000 <p>Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable clinical efficacy in treating hematological malignancies. Nevertheless, the limited persistence of CAR-T cells in vivo remains a major therapeutic hurdle, leading to disease relapse. This review examines current strategies to enhance CAR-T cell durability, focusing on recent advances in CAR structural design, gene editing techniques, ex vivo culture optimization, clinical management approaches, and in vivo preparation. By integrating insights from preclinical studies and clinical trials, we provide a comprehensive analysis of methods to prolong CAR-T cell persistence from a technical perspective and discuss future directions.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 2","pages":"318-336"},"PeriodicalIF":9.9,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461402","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":"Marked Platelet Clumping and Giant Platelets due to GP Ib/ IX Autoantibodies","authors":"Tatsuya Fukuyama, Tomoko Maruhashi, Makiko Mizuguchi, Kumiko Kagawa, Hironobu Shibata, Shuji Ozaki","doi":"10.1002/ajh.70134","DOIUrl":"https://doi.org/10.1002/ajh.70134","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"53 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454639","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}
Wei J. Wang, Qiudan Shen, Mehrnoosh Tashakori, Hong Fang, Wen Shuai, Pei Lin, Zhaoxuan Zhang, Guilin Tang, Wei Wang, Michael A. Linden, Elias J. Jabbour, Tapan M. Kadia, Nicholas J. Short, Naval G. Daver, L. Jeffrey Medeiros, Shimin Hu
<p>Mixed-phenotype acute leukemia (MPAL) is classified under the broader category of acute leukemias of ambiguous lineage in the 5th edition of the WHO Classification of Haematolymphoid Tumors (WHO-HAEM5) and 2022 International Consensus Classification (ICC) [<span>1, 2</span>]. MPAL encompasses acute leukemias showing differentiation along more than one lineage, either in a single population of blasts expressing antigens of multiple lineages (biphenotypic), or multiple populations of blasts, each of a different lineage (bilineal).</p><p>Both the WHO-HAEM5 and the ICC Classification recognize myelodysplastic syndrome (MDS) with biallelic <i>TP53</i> inactivation (i.e., multi-hit <i>TP53</i> mutation) as a distinct disease entity. In the ICC classification, <i>TP53</i> mutation is also considered disease-defining for MDS/acute myeloid leukemia (AML) and AML itself [<span>2-5</span>]. However, the clinicopathologic significance of <i>TP53</i> mutation in MPAL remains poorly characterized. A major challenge in the classification of MPAL cases harboring <i>TP53</i> mutations is that these cases frequently harbor complex karyotypes. Some investigators have proposed reclassifying cases of MPAL with complex karyotype as AML, myelodysplasia-related (AML-MR), given that all acute leukemias with complex karyotypes show similarly poor prognoses, regardless of lineage differentiation [<span>6</span>]. The ICC classification stipulates that MPAL with a complex karyotype should be classified as AML, regardless of the tumor burden of the lymphoid component [<span>2, 7</span>]. However, in the final published version of the ICC classification, MPAL is grouped under the broader category of “Lymphoblastic Neoplasms” [<span>8</span>].</p><p>To address these challenges, we conducted a comprehensive study of 33 patients diagnosed with <i>TP53</i>-mutated MPAL, focusing on cytogenetic and molecular characteristics, dynamic immunophenotypic changes during treatment, and responses to various chemotherapy regimens. Additionally, we evaluated whether <i>TP53</i>-mutated MPAL should be considered a distinct subtype of MPAL, similar to other genetically defined subtypes such as those with <i>BCR::ABL1</i> or <i>KMT2A</i> rearrangements.</p><p>Cases of <i>TP53</i>-mutated MPAL from three collaborative institutions diagnosed since October 1, 2015, according to the immunophenotypic criteria of the ICC classification [<span>2</span>]. The cohort included 16 men and 17 women, with a median age of 65 years (range, 13–78 years) at diagnosis of MPAL (Table 1). At the time of MPAL diagnosis, 17 (51.5%) cases exhibited a biphenotypic immunophenotype, and 16 (48.5%) cases had a bilineal immunophenotype. Among the biphenotypic MPAL cases, 4 were classified as B/myeloid (B/M) and 13 as T/myeloid (T/M). Among the 16 bilineal MPAL cases, 11 were B/M, 3 T/M, and 2 B/T/M subtypes. Within the bilineal MPAL subgroup, 11 cases exhibited a predominant myeloblast population, whereas 5 cases show
{"title":"Mixed-Phenotype Acute Leukemia With Mutated TP53: Genetic Landscape, Therapeutic Response, and Outcomes","authors":"Wei J. Wang, Qiudan Shen, Mehrnoosh Tashakori, Hong Fang, Wen Shuai, Pei Lin, Zhaoxuan Zhang, Guilin Tang, Wei Wang, Michael A. Linden, Elias J. Jabbour, Tapan M. Kadia, Nicholas J. Short, Naval G. Daver, L. Jeffrey Medeiros, Shimin Hu","doi":"10.1002/ajh.70133","DOIUrl":"10.1002/ajh.70133","url":null,"abstract":"<p>Mixed-phenotype acute leukemia (MPAL) is classified under the broader category of acute leukemias of ambiguous lineage in the 5th edition of the WHO Classification of Haematolymphoid Tumors (WHO-HAEM5) and 2022 International Consensus Classification (ICC) [<span>1, 2</span>]. MPAL encompasses acute leukemias showing differentiation along more than one lineage, either in a single population of blasts expressing antigens of multiple lineages (biphenotypic), or multiple populations of blasts, each of a different lineage (bilineal).</p><p>Both the WHO-HAEM5 and the ICC Classification recognize myelodysplastic syndrome (MDS) with biallelic <i>TP53</i> inactivation (i.e., multi-hit <i>TP53</i> mutation) as a distinct disease entity. In the ICC classification, <i>TP53</i> mutation is also considered disease-defining for MDS/acute myeloid leukemia (AML) and AML itself [<span>2-5</span>]. However, the clinicopathologic significance of <i>TP53</i> mutation in MPAL remains poorly characterized. A major challenge in the classification of MPAL cases harboring <i>TP53</i> mutations is that these cases frequently harbor complex karyotypes. Some investigators have proposed reclassifying cases of MPAL with complex karyotype as AML, myelodysplasia-related (AML-MR), given that all acute leukemias with complex karyotypes show similarly poor prognoses, regardless of lineage differentiation [<span>6</span>]. The ICC classification stipulates that MPAL with a complex karyotype should be classified as AML, regardless of the tumor burden of the lymphoid component [<span>2, 7</span>]. However, in the final published version of the ICC classification, MPAL is grouped under the broader category of “Lymphoblastic Neoplasms” [<span>8</span>].</p><p>To address these challenges, we conducted a comprehensive study of 33 patients diagnosed with <i>TP53</i>-mutated MPAL, focusing on cytogenetic and molecular characteristics, dynamic immunophenotypic changes during treatment, and responses to various chemotherapy regimens. Additionally, we evaluated whether <i>TP53</i>-mutated MPAL should be considered a distinct subtype of MPAL, similar to other genetically defined subtypes such as those with <i>BCR::ABL1</i> or <i>KMT2A</i> rearrangements.</p><p>Cases of <i>TP53</i>-mutated MPAL from three collaborative institutions diagnosed since October 1, 2015, according to the immunophenotypic criteria of the ICC classification [<span>2</span>]. The cohort included 16 men and 17 women, with a median age of 65 years (range, 13–78 years) at diagnosis of MPAL (Table 1). At the time of MPAL diagnosis, 17 (51.5%) cases exhibited a biphenotypic immunophenotype, and 16 (48.5%) cases had a bilineal immunophenotype. Among the biphenotypic MPAL cases, 4 were classified as B/myeloid (B/M) and 13 as T/myeloid (T/M). Among the 16 bilineal MPAL cases, 11 were B/M, 3 T/M, and 2 B/T/M subtypes. Within the bilineal MPAL subgroup, 11 cases exhibited a predominant myeloblast population, whereas 5 cases show","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 1","pages":"133-137"},"PeriodicalIF":9.9,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145448207","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}
Chris A. Rees, Dunia Hatabah, Rawan Korman, Fahd Ahmad, Gladstone Airewele, Bolanle Akinsola, Noor Alzraikat, Nitya Bakshi, David C. Brousseau, Kathleen Brown, Andrew D. Campbell, T. Charles Casper, Todd P. Chang, Corrie E. Chumpitazi, Daniel Cohen, Keli D. Coleman, Andrea T. Cruz, Christopher Denton, Angela Ellison, Melanie E. Fields, Monica Harding, Sara Leibovich, Allison Remiker, Nidhi V. Singh, Alexis A. Thompson, Elliott Vichinsky, Anthony Villella, Bridget Wynn, Carlton Dampier, Claudia R. Morris, the Pediatric Emergency Care Research Network (PECARN)
Analysis of the placebo cohort in the STArT trial shows that patient characteristics and hospital site strongly influence time-to-crisis-resolution and total opioid use in children and young adults with sickle cell disease, highlighting the need to account for these factors in the design of future clinical trials.
{"title":"Hospital Variations in Time-To-Crisis-Resolution Among Children and Adolescents With Sickle Cell Disease","authors":"Chris A. Rees, Dunia Hatabah, Rawan Korman, Fahd Ahmad, Gladstone Airewele, Bolanle Akinsola, Noor Alzraikat, Nitya Bakshi, David C. Brousseau, Kathleen Brown, Andrew D. Campbell, T. Charles Casper, Todd P. Chang, Corrie E. Chumpitazi, Daniel Cohen, Keli D. Coleman, Andrea T. Cruz, Christopher Denton, Angela Ellison, Melanie E. Fields, Monica Harding, Sara Leibovich, Allison Remiker, Nidhi V. Singh, Alexis A. Thompson, Elliott Vichinsky, Anthony Villella, Bridget Wynn, Carlton Dampier, Claudia R. Morris, the Pediatric Emergency Care Research Network (PECARN)","doi":"10.1002/ajh.70129","DOIUrl":"10.1002/ajh.70129","url":null,"abstract":"<p>Analysis of the placebo cohort in the STArT trial shows that patient characteristics and hospital site strongly influence time-to-crisis-resolution and total opioid use in children and young adults with sickle cell disease, highlighting the need to account for these factors in the design of future clinical trials.\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":"101 1","pages":"206-212"},"PeriodicalIF":9.9,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440602","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}
A. C. Hristov, T. Tejasvi, R. A. Wilcox, and T. Cutaneous, “Cutaneous T-Cell Lymphomas: 2023 Update on Diagnosis, Risk-Stratification, and Management,” American Journal of Hematology 98, no. 1 (2023 Jan): 193–209, https://doi.org/10.1002/ajh.26760.
In the manuscript, on Page 196, Lines 33–37, it is remarked that “recent consensus recommendations support of the use of peripheral blood flow cytometry in specific patient groups: those with advanced stage (≥ IIB) disease, intractable pruritis, generalize patches/plaques, erythroderma, lymphocytosis, an elevated LDH, or a lack of response to skin-directed therapies.” However, upon review of the primary research (Citation 81) this line references, it appears this statement is misleading. In the article referenced, Vermeer MH, Moins-Teisserenc H, Bagot M, Quaglino P, Whittaker S. Flow cytometry for the assessment of blood tumour burden in cutaneous T-cell lymphoma: towards a standardized approach. Br J Dermatol. 2022 Jul;187(1):21-28. doi: https://doi.org/10.1111/bjd.21053. Epub 2022 May 3. PMID: 35157307; PMCID: PMC9541328., the populations listed on Page 24, Table 2 are listed for “for minimum use of flow cytometry for mycosis fungoides and Sézary syndrome when not performed at all stages” meaning if it is not practical to perform flow cytometry on all patients, these populations at a minimum need to have the testing performed. In your review article as it is currently written, it implies that those are the only groups that flow cytometry should be performed in. This is an important distinction as some patients with a clinically perceived limited stage disease can in fact have a large blood burden making the use of flow cytometry if possible important in all patients as it has significant implications on prognosis and treatment.
A. C. Hristov， T. Tejasvi， R. A. Wilcox，和T. skin，“皮肤t细胞淋巴瘤：2023年诊断、风险分层和管理的最新进展”，《美国血液学杂志》，第98期。1（2023年1月）：193-209,https://doi.org/10.1002/ajh.26760.In手稿，第196页，第33-37行，指出“最近的共识建议支持在特定患者群体中使用外周血流式细胞术：晚期（≥IIB）疾病、顽固性瘙痒、广泛性斑块/斑块、红皮病、淋巴细胞增多、LDH升高或对皮肤定向治疗缺乏反应的患者。”然而，在回顾这一行参考文献的主要研究（引文81）后，这种说法似乎具有误导性。文中引用了Vermeer MH， Moins-Teisserenc H, Bagot M, Quaglino P, Whittaker S.流式细胞术评估皮肤t细胞淋巴瘤血液肿瘤负荷：走向标准化的方法。中华皮肤科杂志，2016,32(1):1- 4。doi: https://doi.org/10.1111/bjd.21053。2022年5月3日。PMID: 35157307;PMCID: PMC9541328。在第24页，表2中列出的人群是“在没有在所有阶段进行流式细胞术的情况下，最少使用流式细胞术治疗蕈样真菌病和sims综合征”，这意味着如果对所有患者进行流式细胞术是不切实际的，这些人群至少需要进行检测。在您目前撰写的综述文章中，它暗示这些是唯一应该进行流式细胞术的组。这是一个重要的区别，因为一些临床认为有限期疾病的患者实际上可能有很大的血液负担，因此，如果可能的话，流式细胞术的使用对所有患者都很重要，因为它对预后和治疗具有重要意义。
{"title":"Erratum to: “Cutaneous T-Cell Lymphomas: 2023 Update on Diagnosis, Risk-Stratification, and Management”","authors":"","doi":"10.1002/ajh.70135","DOIUrl":"10.1002/ajh.70135","url":null,"abstract":"<p>A. C. Hristov, T. Tejasvi, R. A. Wilcox, and T. Cutaneous, “Cutaneous T-Cell Lymphomas: 2023 Update on Diagnosis, Risk-Stratification, and Management,” <i>American Journal of Hematology</i> 98, no. 1 (2023 Jan): 193–209, https://doi.org/10.1002/ajh.26760.</p><p>In the manuscript, on Page 196, Lines 33–37, it is remarked that “recent consensus recommendations support of the use of peripheral blood flow cytometry in specific patient groups: those with advanced stage (≥ IIB) disease, intractable pruritis, generalize patches/plaques, erythroderma, lymphocytosis, an elevated LDH, or a lack of response to skin-directed therapies.” However, upon review of the primary research (Citation 81) this line references, it appears this statement is misleading. In the article referenced, Vermeer MH, Moins-Teisserenc H, Bagot M, Quaglino P, Whittaker S. Flow cytometry for the assessment of blood tumour burden in cutaneous T-cell lymphoma: towards a standardized approach. Br J Dermatol. 2022 Jul;187(1):21-28. doi: https://doi.org/10.1111/bjd.21053. Epub 2022 May 3. PMID: 35157307; PMCID: PMC9541328., the populations listed on Page 24, Table 2 are listed for “for minimum use of flow cytometry for mycosis fungoides and Sézary syndrome when not performed at all stages” meaning if it is not practical to perform flow cytometry on all patients, these populations at a minimum need to have the testing performed. In your review article as it is currently written, it implies that those are the only groups that flow cytometry should be performed in. This is an important distinction as some patients with a clinically perceived limited stage disease can in fact have a large blood burden making the use of flow cytometry if possible important in all patients as it has significant implications on prognosis and treatment.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 1","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433890","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}
Ruah Alyamany, Ahmed Alnughmush, Oleksandr Klymenko, Mohammad Alhousani, Animesh Pardanani, Paul L. Ollila, David S. Viswanatha, Naseema Gangat, Rong He, Ayalew Tefferi
Diagnostic correlates and clonal progression patterns among 91 patients with low (< 1% VAF) or very low (< 0.1% VAF) JAK2 V617F allele burden encountered in routine clinical practice.
{"title":"Low (0.1% to ≤ 1%) or Very Low (0.06% to < 0.1%) JAK2V617F Allele Burden in Routine Testing: Clinical Correlates and Clonal Trajectory","authors":"Ruah Alyamany, Ahmed Alnughmush, Oleksandr Klymenko, Mohammad Alhousani, Animesh Pardanani, Paul L. Ollila, David S. Viswanatha, Naseema Gangat, Rong He, Ayalew Tefferi","doi":"10.1002/ajh.70128","DOIUrl":"10.1002/ajh.70128","url":null,"abstract":"<p>Diagnostic correlates and clonal progression patterns among 91 patients with low (< 1% VAF) or very low (< 0.1% VAF) JAK2 V617F allele burden encountered in routine clinical practice.\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":"101 1","pages":"213-217"},"PeriodicalIF":9.9,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427424","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}
Giovanni Leone, Mattia D'Antiga, Michela Pelloso, Andrea Serafin, Nicolò Danesin, Arianna Bevilacqua, Alessandro Cellini, Francesco Angotzi, Valentina Trimarco, Chiara Briani, Enrico Tiacci, Francesco Piazza, Livio Trentin, Andrea Visentin
<p>Hairy cell leukemia (HCL) is an indolent, rare B-cell lymphoproliferative disorder that accounts for approximately 2% of all leukemias. The disease is characterized by abnormal lymphocytes showing distinctive cytoplasmic projections (“hairy cells”). The hallmark genetic alteration in classic HCL is the <i>BRAF V600E</i> mutation, which promotes malignant proliferation via constitutive MAPK pathway activation [<span>1, 2</span>].</p><p>While HCL primarily involves the bone marrow and spleen, extranodal manifestations, including central nervous system (CNS) involvement, are rare and determine significant diagnostic and therapeutic challenges [<span>3</span>].</p><p>In March 2023, a 75-year-old man with a 30-year history of HCL was admitted to the emergency department (ED) with acute-onset confusion, episodic verbal aggression, and amnesia. Initial management included vortioxetine, with minimal symptomatic improvement. Due to progressive cognitive decline, aphasia, and emesis, he presented again to the ED where he underwent neuroimaging to rule out stroke. Brain computed tomography (CT) and intracranial CT angiography were negative, and neurological evaluation (including NIHSS scoring) excluded acute cerebrovascular pathology. The patient was admitted to the internal medicine unit for further investigation. He had been diagnosed with HCL in 1986 and received multiple lines of therapy: recombinant α-interferon (1986, 1989), splenectomy (1991), pentostatin (11 cycles, 1992) achieved complete remission (CR), cladribine (1999, CR), rituximab-pentostatin (8 cycles, 2009, CR), cladribine (2013; CR), rituximab-pentostatin (8 cycles, 2015, partial response [PR]), rituximab-fludarabine (4 cycles, 2016, PR), and experimental vemurafenib-cobimetinib-obinutuzumab within a clinical trial (2017–2018). The remainder of the medical history was unremarkable aside from HCL. Admission labs revealed a normal blood count except for monocytopenia (Hb 141 g/L, MCV 107.7 fL, PLTs 124 × 10<sup>9</sup>/L, WBC 6.80 × 10<sup>9</sup>/L—N 4.41, Ly 2.15, Mo 0.19), mildly elevated bilirubin (total 24.6 μmol/L, conjugated 7.7 μol/L), and hyperferritinemia (1.734 μg/L). Peripheral blood flow cytometry identified an immunoglobulin light chain kappa-restricted B-lymphocyte population (25% of lymphocytes) co-expressing CD20, CD11c, CD25, CD103, CD123, and CD200.</p><p>Lumbar puncture excluded active infections, autoimmune and paraneoplastic etiologies but showed elevated cerebrospinal fluid (CSF) protein levels (2.33 g/L), lactate (6.2 mmol/L), and pleocytosis (178 cells/μL; 97% mononuclear). Flow cytometry confirmed CNS involvement by HCL, describing a kappa restricted B cell population expressing CD11c, CD19, CD25, and CD103 surface antigens. Morphologic evaluation of CSF demonstrated the presence of a population of cells with large cytoplasm with surface projections and oval nuclei, consistent with hairy cells (Figure 1 A). Further investigations revealed elevated lev
{"title":"An Uncommon Localization of Hairy Cell Leukemia: Central Nervous System Involvement and Response to Ibrutinib—A Case Report and a Review of the Literature","authors":"Giovanni Leone, Mattia D'Antiga, Michela Pelloso, Andrea Serafin, Nicolò Danesin, Arianna Bevilacqua, Alessandro Cellini, Francesco Angotzi, Valentina Trimarco, Chiara Briani, Enrico Tiacci, Francesco Piazza, Livio Trentin, Andrea Visentin","doi":"10.1002/ajh.70126","DOIUrl":"10.1002/ajh.70126","url":null,"abstract":"<p>Hairy cell leukemia (HCL) is an indolent, rare B-cell lymphoproliferative disorder that accounts for approximately 2% of all leukemias. The disease is characterized by abnormal lymphocytes showing distinctive cytoplasmic projections (“hairy cells”). The hallmark genetic alteration in classic HCL is the <i>BRAF V600E</i> mutation, which promotes malignant proliferation via constitutive MAPK pathway activation [<span>1, 2</span>].</p><p>While HCL primarily involves the bone marrow and spleen, extranodal manifestations, including central nervous system (CNS) involvement, are rare and determine significant diagnostic and therapeutic challenges [<span>3</span>].</p><p>In March 2023, a 75-year-old man with a 30-year history of HCL was admitted to the emergency department (ED) with acute-onset confusion, episodic verbal aggression, and amnesia. Initial management included vortioxetine, with minimal symptomatic improvement. Due to progressive cognitive decline, aphasia, and emesis, he presented again to the ED where he underwent neuroimaging to rule out stroke. Brain computed tomography (CT) and intracranial CT angiography were negative, and neurological evaluation (including NIHSS scoring) excluded acute cerebrovascular pathology. The patient was admitted to the internal medicine unit for further investigation. He had been diagnosed with HCL in 1986 and received multiple lines of therapy: recombinant α-interferon (1986, 1989), splenectomy (1991), pentostatin (11 cycles, 1992) achieved complete remission (CR), cladribine (1999, CR), rituximab-pentostatin (8 cycles, 2009, CR), cladribine (2013; CR), rituximab-pentostatin (8 cycles, 2015, partial response [PR]), rituximab-fludarabine (4 cycles, 2016, PR), and experimental vemurafenib-cobimetinib-obinutuzumab within a clinical trial (2017–2018). The remainder of the medical history was unremarkable aside from HCL. Admission labs revealed a normal blood count except for monocytopenia (Hb 141 g/L, MCV 107.7 fL, PLTs 124 × 10<sup>9</sup>/L, WBC 6.80 × 10<sup>9</sup>/L—N 4.41, Ly 2.15, Mo 0.19), mildly elevated bilirubin (total 24.6 μmol/L, conjugated 7.7 μol/L), and hyperferritinemia (1.734 μg/L). Peripheral blood flow cytometry identified an immunoglobulin light chain kappa-restricted B-lymphocyte population (25% of lymphocytes) co-expressing CD20, CD11c, CD25, CD103, CD123, and CD200.</p><p>Lumbar puncture excluded active infections, autoimmune and paraneoplastic etiologies but showed elevated cerebrospinal fluid (CSF) protein levels (2.33 g/L), lactate (6.2 mmol/L), and pleocytosis (178 cells/μL; 97% mononuclear). Flow cytometry confirmed CNS involvement by HCL, describing a kappa restricted B cell population expressing CD11c, CD19, CD25, and CD103 surface antigens. Morphologic evaluation of CSF demonstrated the presence of a population of cells with large cytoplasm with surface projections and oval nuclei, consistent with hairy cells (Figure 1\u0000 A). Further investigations revealed elevated lev","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 1","pages":"160-164"},"PeriodicalIF":9.9,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145404662","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}
Iman Sarami, Jeremy S. Haley, Diane T. Smelser, Adam M. Cook, Joseph J. Vadakara, Yi Ding, David J. Carey
Analysis of whole-exome sequencing data from 92,434 MyCode EHR-linked biobank participants characterizes the spectrum and co-mutation architecture of clonal hematopoiesis and myelodysplastic syndromes (MDS). Age-related increases in variants affecting DNMT3A, TET2, ASXL1, SRSF2, SF3B1, and RUNX1 are observed, with co-mutation patterns distinguishing MDS-associated clonal evolution. Allele balance patterns suggest predominantly somatic origins for most MDS-related variants, while RUNX1 variants show enrichment consistent with germline origin. MDS is associated with elevated cardiovascular risk, whereas CHIP demonstrates no significant cardiovascular association after adjustment for demographic factors.
{"title":"Genetic Landscape of Myelodysplastic Syndrome and Clonal Hematopoiesis: Insights From Whole Exome Sequencing of 90 000 Individuals","authors":"Iman Sarami, Jeremy S. Haley, Diane T. Smelser, Adam M. Cook, Joseph J. Vadakara, Yi Ding, David J. Carey","doi":"10.1002/ajh.70113","DOIUrl":"10.1002/ajh.70113","url":null,"abstract":"<p>Analysis of whole-exome sequencing data from 92,434 MyCode EHR-linked biobank participants characterizes the spectrum and co-mutation architecture of clonal hematopoiesis and myelodysplastic syndromes (MDS). Age-related increases in variants affecting <i>DNMT3A</i>, <i>TET2</i>, <i>ASXL1</i>, <i>SRSF2</i>, <i>SF3B1</i>, and <i>RUNX1</i> are observed, with co-mutation patterns distinguishing MDS-associated clonal evolution. Allele balance patterns suggest predominantly somatic origins for most MDS-related variants, while RUNX1 variants show enrichment consistent with germline origin. MDS is associated with elevated cardiovascular risk, whereas CHIP demonstrates no significant cardiovascular association after adjustment for demographic factors.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 12","pages":"2448-2451"},"PeriodicalIF":9.9,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397488","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号