EJHaem最新文献

{"title":"Efficacy of Total-Body Irradiation-based Intensified Myeloablative Regimens for Acute Leukemia—An International Collaborative Study","authors":"Yasuyuki Arai,&nbsp;Ruta Brazauskas,&nbsp;Naya He,&nbsp;A. Samer Al-Homsi,&nbsp;Saurabh Chhabra,&nbsp;Minoo Battiwalla,&nbsp;Masamitsu Yanada,&nbsp;Amir Steinberg,&nbsp;Miguel Angel Diaz Perez,&nbsp;Sanghee Hong,&nbsp;Junya Kanda,&nbsp;Asad Bashey,&nbsp;Haydar A. Frangoul,&nbsp;Sherif M. Badawy,&nbsp;Leo F. Verdonck,&nbsp;Hillard M. Lazarus,&nbsp;Jean A. Yared,&nbsp;Hasan Hashem,&nbsp;Akshay Sharma,&nbsp;Mahmoud Aljurf,&nbsp;Ajoy L. Dias,&nbsp;Muhammad Bilal Abid,&nbsp;Baldeep Wirk,&nbsp;César O. Freytes,&nbsp;Amer M. Zeidan,&nbsp;Usama Gergis,&nbsp;Amer Beitinjaneh,&nbsp;Medhat Askar,&nbsp;Jeffrey J. Pu,&nbsp;Leslie E. Lehmann,&nbsp;Hemalatha G. Rangarajan,&nbsp;William A. Wood,&nbsp;Shahrukh Hashmi,&nbsp;Shingo Yano,&nbsp;Shinichi Kako,&nbsp;Yukiyasu Ozawa,&nbsp;Noriko Doki,&nbsp;Yoshinobu Kanda,&nbsp;Takahiro Fukuda,&nbsp;Yuta Katayama,&nbsp;Tatsuo Ichinohe,&nbsp;Junji Tanaka,&nbsp;Takanori Teshima,&nbsp;Shinichiro Okamoto,&nbsp;Yoshiko Atsuta,&nbsp;Wael Saber","doi":"10.1002/jha2.70061","DOIUrl":"https://doi.org/10.1002/jha2.70061","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In this study, we compared outcomes of intensified myeloablative conditioning regimens using large registry data from Japan (Japanese Society for Transplantation and Cellular Therapy) and the United States (Center for International Blood and Marrow Transplant Research).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adult patients who underwent their first myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia in remission between 2010 and 2018 using conditioning regimens of cyclophosphamide plus total-body irradiation (CY/TBI), CY/TBI+cytarabine (AraC), or CY/TBI+etoposide (VP16) were included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The acute myeloid leukemia (AML) cohort (<i>N</i> = 480, 38.8%) indicated that overall survival (OS) was poorer in CY/TBI+AraC (hazard ratio [HR] 1.46, <i>p</i> &lt; 0.001) and CY/TBI+VP16 (HR 1.39, <i>p</i> = 0.059) compared to CY/TBI. Relapse was not suppressed, while treatment-related mortality (TRM) was significantly higher (HR 1.78 and 1.74, <i>p</i> &lt; 0.001 and 0.018, respectively). In the acute lymphoblastic leukemia (ALL) cohort (<i>N</i> = 3901, 61.2%), OS was comparable among these regimens. With intensified regimens, relapse was significantly suppressed in CY/TBI+VP16 (HR 0.74, <i>p</i> = 0.005), while TRM was higher (HR 1.21, <i>p</i> = 0.077). No interactions were observed regarding the country.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In AML adding AraC and VP16 to CY/TBI had an adverse effect on OS. Conversely, in ALL, adding VP16 or AraC to CY/TBI did not affect survival, but the addition of VP16 reduced the risk of relapse.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical Trial Registration</h3>\u0000 \u0000 <p>The authors have confirmed clinical trial registration is not needed for this submission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System—Outcomes in Finland: A Nationwide Population-Based Study","authors":"Mikko Moisala,&nbsp;Ilja Kalashnikov,&nbsp;Niklas Haataja,&nbsp;Sirpa Leppä,&nbsp;Marjukka Pollari","doi":"10.1002/jha2.70021","DOIUrl":"https://doi.org/10.1002/jha2.70021","url":null,"abstract":"<p>Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy commonly presenting with a rapid disease course and poor prognosis. Recent clinical trials have indicated improved treatment outcomes in a highly selected patient population. However, real-world data focusing on long-term, population-based outcomes remain largely unexplored. We analyzed trends in relative survival (RS) in patients diagnosed with PCNSL in Finland from 1995 to 2018. We identified 718 PCNSL patients from the comprehensive Finnish Cancer Registry (FCR) (51% males, median age 67.8 years). For the entire cohort, 5-year overall survival (OS) and RS rates were 21% and 22%, respectively. The 2-year RS was 39% for patients younger than 75 years and 14% for older patients. A gradual increase in the 2-year RS rate was observed over successive chronological diagnostic periods. Age above 75 years at diagnosis (HR 3.65, 95% CI: 2.73–4.89) and diagnosis during a calendar period of 1995–2006 (HR 1.30, 95% CI: 1.10–1.53) were associated with a significantly increased risk of death. An increase in the number of patients diagnosed with PCNSL during the study period was confirmed, and the prognosis of patients diagnosed after the age of 75 years continues to be dismal.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flow Cytometry Analysis of Mesenchymal Stem Cells: A Predictive Biomarker for Leukemia Transformation in Myelodysplastic Syndrome","authors":"Mireia Atance,&nbsp;Cristina Serrano,&nbsp;Carlos Soto,&nbsp;Juan Manuel Alonso-Domínguez,&nbsp;Carlos Blas,&nbsp;Raquel Mata,&nbsp;Tamara Castaño,&nbsp;Sara Perlado,&nbsp;Teresa Arquero,&nbsp;Jose Luis López-Lorenzo,&nbsp;M. Ángeles Pérez,&nbsp;Belen Rosado,&nbsp;Rafael Martos,&nbsp;Ana Rio-Machin,&nbsp;Pilar Llamas-Sillero,&nbsp;Rocio N. Salgado,&nbsp;Juana Serrano-López","doi":"10.1002/jha2.70059","DOIUrl":"https://doi.org/10.1002/jha2.70059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study evaluates the prognostic value of bone marrow-derived mesenchymal stem cells (MSCs) in predicting the progression of Myelodysplastic Syndrome (MDS) to Acute Myeloid Leukemia (AML).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MSC-like cells were analyzed using flow cytometry in a cohort of 49 MDS patients, including transformed and non-transformed groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A non-hematopoietic CD13-bright cell population, enriched for MSC markers CD105 and CD90, was identified in 80% of patients at diagnosis. Elevated of these MSC-like cells were significantly associated with earlier progression to leukemia and reduced overall survival. Multivariate analysis confirmed MSC content as an independent predictor of leukemia transformation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MSC-like cell content at MDS diagnosis may serve as a novel biomarker of predicting malignant transformation to AML. Further validation in larger cohorts and better phenotypic characterization of this cell population are needed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The authors have confirmed clinical trial registration is not needed for this submission</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “What is the Origin of the Normal Ranges of Blood Cell Counts? An Evolutionary Perspective”","authors":"","doi":"10.1002/jha2.70057","DOIUrl":"https://doi.org/10.1002/jha2.70057","url":null,"abstract":"<p>Zala M, Alcazer V, Largeaud L, Sujobert P. What is the origin of the normal ranges of blood cell counts? An evolutionary perspective. eJHaem. 2025;6:e1073. https://doi.org/10.1002/jha2.1073</p><p>In the article, Figures 1 and 2; supporting information Figures S1 and S2 contained errors. The corrected figures are shown below and the supporting information figures have been updated in the online version of the article.</p><p>We apologize for this error.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sporadic Porphyria Cutanea Tarda, Cutaneous Sarcoidosis, and Compound Heterozygosity of HFE Mutations Cys282Tyr and His63Asp—A Case Report","authors":"Jowon L. Kim,&nbsp;Richard Crawford,&nbsp;Ian Marie Lano,&nbsp;Hayley Merkeley","doi":"10.1002/jha2.70054","DOIUrl":"https://doi.org/10.1002/jha2.70054","url":null,"abstract":"<p>Porphyria cutanea tarda (PCT) is caused by inherited or acquired defects of uroporphyrinogen decarboxylase (UROD) in the heme biosynthetic pathway. Altered iron homeostasis via hemochromatosis gene (HFE) mutations is one of many susceptibility factors associated with the sporadic form of PCT. Though sarcoidosis is not commonly associated with PCT, prior reports of hepatic sarcoidosis postulated that hepatic granulomas affect UROD activity by direct interference or immunological mechanisms. Here we describe a case of acquired PCT in the setting of (HFE):c.845G&gt;A (p.Cys282Tyr) and (HFE):c.187C&gt;G (p.His63Asp) compound heterozygosity, hepatic steatosis, and cutaneous sarcoidosis.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Langerhans Cell Histiocytosis With MAP2K1E102_I103del Mutation Successfully Treated With Trametinib","authors":"Min Lang,&nbsp;Long Chang,&nbsp;Xin-xin Cao","doi":"10.1002/jha2.70067","DOIUrl":"https://doi.org/10.1002/jha2.70067","url":null,"abstract":"<p>The discovery of the MAPK pathway mutations in lesions of patients with Langerhans cell histiocytosis (LCH) has made targeted therapy an important therapeutic approach for these patients. Theoretically, the RAF-independent mutation <i>MAP2K1^E102_I103del</i> is naturally resistant to allosteric MEK inhibitors. We report a dramatic response to MEK inhibitor trametinib in a case of LCH with <i>MAP2K1^E102_I103del</i> mutation, which indicates that trametinib is worth trying in recurrence and refractory LCH patients with <i>MAP2K1^E102_I103del</i>.</p><p><b>Trial Registration</b>: The authors have confirmed clinical trial registration is not needed for this submission.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What Is Acute Myeloid Leukemia?","authors":"Daniel Mazza Matos,&nbsp;Eduardo Magalhaes Rego","doi":"10.1002/jha2.70063","DOIUrl":"https://doi.org/10.1002/jha2.70063","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The recently published fifth edition of the World Health Organization (WHO) Classification and the International Consensus Classification (ICC) of myeloid neoplasms diverge in their definitions of acute myeloid leukemia (AML). Fundamentally, this current situation is problematic for two main reasons. First, the disagreement between the WHO and ICC reflects a conceptual conflict regarding the necessary and sufficient conditions for diagnosing AML. This leads to some confusion in areas such as nomenclature, therapeutic eligibility, clinical trial selection, and guidelines development. Second, in clinical practice, the two systems may assign different diagnoses to the same patient with a single disease entity. Such inconsistencies are unacceptable and highlight the urgent need for harmonization between the two classification systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Topic</h3>\u0000 \u0000 <p>In response, we put forward a proposal based on an unorthodox approach that combines philosophical reflections on essential and accidental properties with the latest clinical evidence concerning “AML subtypes with defining genetic abnormalities,” with the aim of initiating the unification of the WHO and ICC classification systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Implications</h3>\u0000 \u0000 <p>In this review, we propose a preliminary recommendation for a unified WHO-ICC classification of five AML subtypes: AML with <i>PML</i>::<i>RARA</i> rearrangement, AML with <i>NPM1</i> mutation, AML with <i>KMT2A</i> rearrangement, AML with <i>MECOM</i> rearrangement, and AML with in-frame bZIP <i>CEBPA</i>. We hope that these initial efforts can be followed by a more definitive attempt to unify the WHO and ICC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The authors have confirmed clinical trial registration is not needed for this submission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teclistamab-Induced Remission of Chronic Immune Thrombocytopenia in a Patient With Multiple Myeloma","authors":"Renata Quevedo-Salazar,&nbsp;José Miguel Yáñez-Reyes,&nbsp;Elías Eugenio González-López,&nbsp;Ana Varela-Constantino,&nbsp;Andrés Gómez-De León,&nbsp;Xitlaly Judith González-Leal,&nbsp;David Gómez-Almaguer","doi":"10.1002/jha2.70062","DOIUrl":"https://doi.org/10.1002/jha2.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>We report the case of a 76-year-old woman with refractory immune thrombocytopenia (ITP) and multiple myeloma (MM) who achieved remission of both conditions following teclistamab treatment. After failing multiple ITP therapies, her platelet count continued to decline. Initiation of teclistamab led to a rapid and sustained platelet increase, alongside MM response with measurable residual disease (MRD) negativity. Notably, remission was achieved after only four full doses, and the patient has remained in complete remission since. This case highlights teclistamab as a potential treatment for refractory ITP, suggesting a novel role for B-cell maturation antigen (BCMA)-targeted therapies in autoimmune diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The authors have confirmed clinical trial registration is not needed for this submission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender Disparity in Enrollment in Clinical Trials for Hairy Cell Leukemia Treatments in the Last 40 Years","authors":"Oscar F. Borja-Montes,&nbsp;Anna Bode,&nbsp;Tomas Escobar-Gil,&nbsp;Alejandro Toro-Pedroza,&nbsp;Narandranath Epperla,&nbsp;Leslie A. Andritsos","doi":"10.1002/jha2.70065","DOIUrl":"https://doi.org/10.1002/jha2.70065","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hairy Cell Leukemia (HCL) is a B-cell lymphoproliferative disorder that predominantly affects males, yet recent evidence suggests a notable gender participation gap in HCL clinical trials. This study aims to characterize that disparity and explore potential factors contributing to the under-enrollment of females.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this descriptive, retrospective study, we searched EMBASE, PUBMED, Cochrane Central, and ClinicalTrials.gov from January 1983 to December 2023 for publications on clinical trials (CT) in HCL, descriptive statistical analysis of all the sociodemographic variables was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analyzed 57 clinical trials totaling 4595 HCL patients, with 79.1% male and 20.9% female participants. The male-to-female ratio declined from 5.91 (1983–1993) to 4.19 (2014–2023). Although the gender gap narrowed over time, female participation slightly decreased to 19.2% in the most recent period (2014–2023).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Female enrollment in HCL clinical trials remains disproportionately low compared to incidence rates, underscoring the need to address underlying barriers to improve equity in clinical research and treatment outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The authors have confirmed clinical trial registration is not needed for this submission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Iptacopan Versus C5 Inhibitors in Complement Inhibitor-Naive Patients With Paroxysmal Nocturnal Haemoglobinuria","authors":"Matthew Holt,&nbsp;Richard J. Kelly,&nbsp;Jilles M. Fermont,&nbsp;Soudeh Ansari,&nbsp;Marion Dahlke,&nbsp;Isabelle Brindel,&nbsp;Lynda Maafa,&nbsp;Flore Sicre de Fontbrune,&nbsp;Régis Peffault de Latour","doi":"10.1002/jha2.70055","DOIUrl":"https://doi.org/10.1002/jha2.70055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Paroxysmal nocturnal haemoglobinuria (PNH) is characterised by haemolytic anaemia, bone marrow failure and thrombosis. The single-arm phase 3 APPOINT-PNH trial (NCT04820530) investigating iptacopan monotherapy in complement inhibitor-naive patients demonstrated significant haemoglobin concentration improvements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used target trial emulation to retrospectively predict outcomes if APPOINT-PNH trial patients had received C5 inhibitors instead of iptacopan. Estimates were derived from the real-world APPEX cohort treated with routine C5 inhibitors. The study used benchmarking and comparative effectiveness to evaluate the haematological response in APPOINT-PNH if patients had received C5 inhibitors. Treatment effect was estimated using propensity scores to model the probability of trial inclusion based on baseline covariates, followed by fitting an outcome model to the APPEX cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The analysis of 125 patients showed all estimated treatment effects (95% confidence interval) favoured iptacopan over C5 inhibitors: differences in the proportion of patients achieving haemoglobin increase from baseline of ≥ 2 g/dL, 68.2% (40.9–95.6); haemoglobin levels of ≥ 12 g/dL, 53.4% (31.4–75.3); transfusion independence, 38.8% (15.1–62.5); ratio of percent change from baseline in lactate dehydrogenase levels, 0.51 (0.40–0.67); change from baseline in reticulocytes, −75.5 × 10⁹/L (−106.9, −44.2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Results indicate C5 inhibitor-naive patients with PNH may experience greater haematological response with iptacopan than with C5 inhibitors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT05842486</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}