American Journal of Hematology最新文献

{"title":"Biology and Management of Acute Myeloid Leukemia With Mutated NPM1","authors":"Evan C. Chen, Shai Shimony, Marlise R. Luskin, Richard M. Stone","doi":"10.1002/ajh.27600","DOIUrl":"https://doi.org/10.1002/ajh.27600","url":null,"abstract":"Mutations in nucleophosmin 1 (<jats:italic>NPM1</jats:italic>) are diseased‐defining genetic alterations encountered in approximately one‐third of cases of acute myeloid leukemia (AML). A mutation in <jats:italic>NPM1</jats:italic> confers a more favorable prognosis; however, clinical outcomes of <jats:italic>NPM1</jats:italic>–mutated AML (<jats:italic>NPM1</jats:italic><jats:sup>mut</jats:sup> AML) are diverse due to the heterogeneity of disease biology, patient characteristics, and treatment received. Research over the last two decades has dramatically expanded our understanding of the biology of <jats:italic>NPM1</jats:italic><jats:sup>mut</jats:sup> AML and led to the development of new therapeutic approaches and strategies for monitoring measurable residual disease (MRD). Here, we review <jats:italic>NPM1</jats:italic><jats:sup>mut</jats:sup> AML with a practical focus on the current treatment landscape, the role of MRD in guiding management, and emerging therapies, including menin inhibitors.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"6 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083756","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":"2025 Clinical Trials Update on Hemophilia, VWD, and Rare Inherited Bleeding Disorders","authors":"Debbie Jiang, Michael Wang, Allison P. Wheeler, Stacy E. Croteau","doi":"10.1002/ajh.27602","DOIUrl":"https://doi.org/10.1002/ajh.27602","url":null,"abstract":"Clinical trial programs for inherited bleeding disorders feature an array of innovative prophylaxis options: engineered clotting factor concentrates, FVIIIa mimetics, gene therapies, and biologics to bolster thrombin generation (rebalancing agents). Increasingly, non-hemophilia bleeding disorders and a broader demographic (females, children, and infants) are being incorporated into study populations. Ongoing clinical trials broadly address three themes: (1) indication expansion for licensed therapeutics in previously uninvestigated patient subgroups or clinical scenarios, (2) evaluation of efficacy and safety among other bleeding disorders such as von Willebrand disease, platelet function defects, and rare clotting factor deficiencies, and (3) longitudinal assessment of approved treatments particularly with regard to longer-term efficacy outcomes such as musculoskeletal health and treatment-specific safety outcomes including thrombotic risk and liver health. With these new prophylaxis modalities, providers must have a nuanced understanding of each therapy's mechanism of action, advantages, side effect profile, therapeutic limitations, and impact on hemostasis and laboratory monitoring. Treatment is no longer “one size fits all.” Rather, management is tailored to individual needs and preferences. Here, we review active investigational trials and highlight promising approaches in preclinical development, expanding the innovative, complex landscape of inherited bleeding disorders therapeutics.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"12 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143084102","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":"Sharpening the Tools to Get the Edge on Leukemia","authors":"Shai Shimony, Jacqueline S. Garcia","doi":"10.1002/ajh.27622","DOIUrl":"https://doi.org/10.1002/ajh.27622","url":null,"abstract":"<h2> Conflicts of Interest</h2>\u0000<p>J. Garcia has received research grants from AbbVie, Newave, Pfizer, and Genentech, and was an advisory board member or on the steering committee for AbbVie, Genentech, and Servier. S. shimony has no conflicts to declare.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"123 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143084115","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":"Balancing the Scales: Optimizing Reporting of Infection Rates in Clinical Trials of Bispecific Antibodies in Multiple Myeloma.","authors":"Joshua Richter, Madhav V Dhodapkar, Mengying Li, Mina Awad, Christian Hampp, Kate Knorr, Glenn Kroog, Tito Roccia, Naresh Bumma","doi":"10.1002/ajh.27618","DOIUrl":"https://doi.org/10.1002/ajh.27618","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063130","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":"Dirt Under the Finger-Nails—More Malignant Than Malignancy","authors":"Sumeet Mirgh, Sujata Lall, Sachin Punatar, Anant Gokarn, Nishant Jindal, Akanksha Chichra, Vivek Bhat, Navin Khattry","doi":"10.1002/ajh.27615","DOIUrl":"https://doi.org/10.1002/ajh.27615","url":null,"abstract":"A young boy developed steroid refractory GVHD post haploidentical transplant for relapsed B-ALL. He was on systemic immunosuppression with two immunosuppressants, and had history of CMV reactivation and tuberculosis. Eight months post-transplant, he was hospitalized with multi-drug-resistant gram-negative sepsis, and during the same episode, he developed penile lesions which progressed to dry gangrene of glans-penis. Fusarium grew in blood and penile lesions. On retrospective thinking, it was discerned that his onychomycoses were the probable cause of his penile lesions with hematogenous dissemination, as nails also grew Fusarium. This case highlights the need for a vigilant skin and nail examination in immunocompromised patients. This is important for two perspectives. First, cultures from potential colonized sources can help early identification and escalation of treatment. Secondly, appropriate precautions and treatment of superficial infections can help prevent dissemination.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"36 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056320","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":"Non‐Transfusion‐Dependent Thalassemia: An Image Gallery Worth a Thousand Words","authors":"Khaled M. Musallam, Sujit Sheth, Thomas D. Coates, Hanny Al‐Samkari, Maria Domenica Cappellini, Kevin H. M. Kuo, Vip Viprakasit, Ali T. Taher","doi":"10.1002/ajh.27621","DOIUrl":"https://doi.org/10.1002/ajh.27621","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"16 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056309","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 Sleep Traits With Venous Thromboembolism: Prospective Cohort and Mendelian Randomization Studies","authors":"Yuqian Li, Feifei Sun, Chao Ji, Honghao Yang, Zheng Ma, Yuhong Zhao, Zhiying Zhao, Yang Xia","doi":"10.1002/ajh.27620","DOIUrl":"https://doi.org/10.1002/ajh.27620","url":null,"abstract":"Previous research indicates an association between sleep traits and venous thromboembolism (VTE) risk, though causal relationships remain uncertain. This study evaluated combined and independent associations between sleep traits and VTE risk using UK Biobank data and explored the causal associations between sleep traits and VTE through two-sample Mendelian randomization (MR) analyses. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations between the healthy sleep score, as well as individual sleep traits (including sleep duration, insomnia, daytime sleepiness, snoring, and chronotype), and VTE risk were calculated using Cox proportional hazards regression models. Additionally, the two-sample MR analyses used the inverse-variance weighted method to determine odds ratios (ORs) and 95% CIs for causal associations. In the cohort analysis, 314 077 VTE–free participants were followed for a median of 12.3 years, during which 7176 VTE cases occurred. In comparison to those with a sleep score of 0–1, participants with a score of 5 were associated with a 30% lower risk of VTE (HR: 0.70; 95% CI: 0.61–0.80). A U-shaped association was noted between sleep duration and VTE risk. Both short (≤ 6 h) and long (≥ 9 h) sleep durations increased VTE risk. Excessive daytime sleepiness, snoring, and evening chronotype also elevated VTE risk. MR analyses supported a causal relationship for short sleep duration (OR: 1.24; 95% CI: 1.04–1.47) with VTE risk, while other sleep traits showed no causal association. These findings underscore the importance of optimal sleep in reducing VTE risk.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"43 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056316","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":"Elderly Patients With Aplastic Anemia: Treatment Patterns and Outcomes in the Real World","authors":"Bruno Fattizzo, Carmelo Gurnari, Sabrina Giammarco, Antony Ricchiuti, Hussein Awada, Marta Bortolotti, Nicole Galli, Giacinto Luca Pedone, Francesco Versino, Dario Consonni, Roochi Trikha, Shreyans Gandhi, Simona Sica, Jaroslaw P. Maciejewski, Austin Kulasekararaj, Wilma Barcellini","doi":"10.1002/ajh.27611","DOIUrl":"https://doi.org/10.1002/ajh.27611","url":null,"abstract":"We retrospectively analyzed a large international cohort of 1113 patients with aplastic anemia to evaluate treatment choice and outcome in elderly patients as compared with a younger population. Overall, 319 (29%) patients were &gt; 60 years old at diagnosis (60–64 years (<i>n</i> = 85), 106 65–69 years (<i>n</i> = 106), and 128 &gt; 70 years (<i>n</i> = 128)). Elderly patients showed a more severe thrombocytopenia at onset and a significantly lower overall response (complete plus partial) to first-line therapy at 6 months as compared to younger patients (47% vs. 65%, <i>p</i> &lt; 0.0001), irrespective of treatment modality (ATG or CyA combinations, eltrombopag, or androgens); 27 (8%) received transplant as second line therapy and 11 (41%) died, mainly due to transplant complications. The rate of evolution to MDS was greater in elderly patients (12% vs. 7% in younger AA, <i>p</i> = 0.002), whilst the rate of evolution to AML was similar (1.8 vs. 1.3%). By multivariable analysis, older age remained the main factor associated with mortality [HR 1.64 (95% CI 1.5–1.7), <i>p</i> &lt; 0.001], followed by disease severity by Camitta classification [HR 2.24 (95% CI 1.6–3.1) for severe AA; HR 3.8 (95% CI 2.4–6) for very severe AA], and male gender [1.45 (95% CI 1.1–1.8), <i>p</i> &lt; 0.001]. In this large study, elderly AA was associated with inferior outcome even in the TPO-RA era, highlighting the need for further optimization of clinical management.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"52 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055300","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":"Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy","authors":"Michael Hallek","doi":"10.1002/ajh.27546","DOIUrl":"10.1002/ajh.27546","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Disease Overview&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Diagnosis&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as typical B-cell markers.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Prognosis and Staging&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Two clinical staging systems, Rai and Binet, provide prognostic information by using the results of physical examination and blood counts. Various biological and genetic markers provide additional prognostic information. Deletions of the short arm of chromosome 17 (del(17p)) and/or mutations of the &lt;i&gt;TP53&lt;/i&gt; gene predict a shorter time to progression with most targeted therapies. The CLL international prognostic index (CLL-IPI) integrates genetic, biological, and clinical variables to identify distinct risk groups of patients with CLL. The CLL-IPI retains its significance in the era of targeted agents, but the overall prognosis of CLL patients with high-risk stages has improved.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Therapy&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Only patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. When treatment is indicated, several therapeutic options exist: combinations of the BCL2 inhibitor venetoclax with obinutuzumab, or venetoclax with ibrutinib, or monotherapy with one of the inhibitors of Bruton tyrosine kinase (BTK). At relapse, the initial treatment may be repeated if the treatment-free interval exceeds 3 years. If the leukemia relapses earlier, therapy should be changed using an alternative regimen.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Future Challenges&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Combinations of targeted agents now provide efficient therapies with a fixed duration that generate deep and durable remissions. These fixed-duration therapies have gained territory in the management of CLL, as they are cost-effective, avoid the emergence of resistance, and offer treatment free time to the patient. The cure rate of these novel combination regimens is unknown. Moreover, the optimal sequencing of targeted therapies remains to be determined. A medical challenge is to treat patien","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 3","pages":"450-480"},"PeriodicalIF":10.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27546","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050827","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 and Prognostic Significance of Additional Chromosomal Abnormalities at Diagnosis of Chronic Myeloid Leukemia","authors":"Jiří Mayer, Petra Čičátková, Lenka Kováčová, Marie Jarošová, Michal Karas, Pavel Jindra, Hana Klamová, Kateřina Machová Poláková, Olga Černá, Eduard Cmunt, Petra Bělohlávková, Pavel Žák, Edgar Faber, Tomáš Papajík, Lukáš Stejskal, Ivana Ježíšková, Barbora Weinbergerová, Tomáš Jurček, Tomáš Horňák, Daniela Žáčková, Šárka Ransdorfová, Milena Holzerová, Tomáš Pavlík","doi":"10.1002/ajh.27608","DOIUrl":"https://doi.org/10.1002/ajh.27608","url":null,"abstract":"The influence of t(v;22) sole, major route ACAs all (+8, <i>n</i> = 14; +Ph, <i>n</i> = 10; +19, <i>n</i> = 1), and -Y sole on progression-free survival. Survival curves are compared with those of patients with the standard t(9;22) translocation. Other ACAs or complex karyotypes did not influence survival.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"55 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050835","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}