American Journal of Hematology最新文献

{"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}

{"title":"Intravenous Iron Associated Hypophosphatemia: Much More Than a Laboratory Curiosity","authors":"Michael Auerbach,&nbsp;Myles Wolf","doi":"10.1002/ajh.27599","DOIUrl":"10.1002/ajh.27599","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 5","pages":"752-754"},"PeriodicalIF":10.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27599","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987436","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":"Residual Cerebrovascular Morbidity Despite Treatment in Pediatric Sickle Cell Disease Highlights Opportunities for Earlier, Intensified Monitoring and Treatment","authors":"Giulia Reggiani,&nbsp;Beatrice Coppadoro,&nbsp;Maria Paola Boaro,&nbsp;Roberta Trapanese,&nbsp;Ilaria Baido,&nbsp;Alessandra Biffi,&nbsp;Federica Viaro,&nbsp;Alessio Pieroni,&nbsp;Matteo Minerva,&nbsp;Giovanna Barcelos,&nbsp;Renzo Manara,&nbsp;Claudia Baracchini,&nbsp;Raffaella Colombatti","doi":"10.1002/ajh.27596","DOIUrl":"10.1002/ajh.27596","url":null,"abstract":"&lt;p&gt;We read with great interest the article by Casella et al. [&lt;span&gt;1&lt;/span&gt;] which reported the results of the HU Prevent Trial. Regardless of the limitations acknowledged by the authors, Casella's study suggests that Hydroxyurea (HU) may have neuroprotective effect in very young children with sickle cell disease (SCD) and support a phase III study to encourage the early use of HU in all infants with SCD. While many advances have been made in the understanding of the pathophysiology and the identification of the cornerstones of comprehensive care to reduce mortality in the first years of life, cerebral vasculopathy remains a cause of acute mortality and long-term morbidity with impact on quality of life [&lt;span&gt;2-4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Here, we report on cerebral vasculopathy morbidity in a longitudinal pediatric SCD natural history cohort in a high-income country, showing both the benefit of HU in reducing cerebral vasculopathy but also the need to intensify treatments in young children in order to reduce the serious impact of cerebral complications later in life. We performed a retrospective analysis using data from children with SCD who, at age of diagnosis, were prospectively enrolled in the SCD Natural History Study, which began in December 1, 2007 and is an ongoing, longitudinal follow-up study recording information on the physical examination, laboratory parameters, acute and chronic complications during every outpatient and inpatient visit since diagnosis. The censoring date was December 31, 2020, or the date of death, enrollment in a randomized clinical trial assessing new therapeutic drugs, transfer to a new center, or Hematopoietic Stem Cell Transplantation (HSCT). The study was approved by the Research Ethic Committee of Padua University Hospital, and written informed consent was obtained by each caregiver. The Italian Association of Pediatric Hematology Oncology (AIEOP) guidelines were used to guide acute event treatment, monitoring of chronic organ damage and standardize treatment with Hydroxyurea (HU), red blood cell transfusion and HSCT, as well as management of acute and chronic complications (6–7). HU was indicated in case of more than two vaso-occlusive-crisis (VOC) per year or chronic anemia with hemoglobin &lt; 8 g/dL. Regarding cerebral vasculopathy, the standard care included annual Transcranial doppler (TCD) from age 2 and Magnetic Resonance Imaging/Magnetic Resonance Angiography (MRI/MRA) from 6 years, every 2 years, or earlier in case of abnormal TCD. In this analysis, we evaluated event-free survival (EFS) and cumulative incidence analysis of a composite neurological event defined as the occurrence of at least one of the following: clinical neurological event (transient ischemic attack or stroke), abnormal/conditional TCD, new stenosis at MRA, new silent cerebral infarct (SCI) at MRI.&lt;/p&gt;&lt;p&gt;Fisher and chi-square tests were used to compare categorical variables. Kaplan–Meier method was used to estimate survival probabilities, ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"717-719"},"PeriodicalIF":10.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27596","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987121","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}