EJHaem最新文献

{"title":"Overall Survival of Patients With Pyruvate Kinase Deficiency in the UK: A Real-World Study","authors":"Patrick Foy, Sara Higa, Jing Zhao, Karabo Keapoletswe, Lorena Cirneanu, Alessandra Venerus, Louise Raiteri, Erik Landfeldt, Eleonora Iob, Louise Lombard, Junlong Li, Erin Zagadailov","doi":"10.1002/jha2.70009","DOIUrl":"https://doi.org/10.1002/jha2.70009","url":null,"abstract":"<p>To the Editor,</p><p>Pyruvate kinase (PK) deficiency is a rare, congenital haemolytic anaemia, with an estimated diagnosed prevalence in Western populations of between 3.2 and 8.5 per million [<span>1</span>]. Patients with PK deficiency have a spectrum of significant, long-term complications that include iron overload, liver disease, osteopenia/bone fragility, biliary events and pulmonary hypertension [<span>1-4</span>]. It has been reported that some of these clinical complications, including iron overload and pulmonary hypertension, are associated with a lower health-related quality of life in patients with PK deficiency [<span>5</span>]. The overlap in clinical and haematological features of PK deficiency with other hereditary anaemias, as well as its clinical heterogeneity, often hinders diagnosis of the disease [<span>6</span>]. Due to the rarity of PK deficiency and its common misdiagnosis [<span>6</span>], the current understanding of the disease burden and the impact of PK deficiency on patient survival is limited. A better understanding of survival outcomes could improve disease management, timing of treatment intervention and healthcare resource utilisation.</p><p>To better characterise the survival outcomes of these patients, this retrospective cohort study evaluated overall survival (OS) of patients with PK deficiency and matched non-PK deficiency controls in the United Kingdom (UK), using data from the Clinical Practice Research Datalink (CPRD). The CPRD is comprised of two longitudinal primary care databases, CPRD Aurum and CPRD GOLD, which cover 20% and 4% of the UK population, respectively. These databases were linked to secondary care databases, Hospital Episode Statistics and the Office of National Statistics [<span>7</span>].</p><p>Cases with PK deficiency included males and females of any age with at least one coded clinical term within the CPRD Aurum/GOLD databases (MedCode) for PK deficiency at any time in their medical history (Table S1). Each case was matched with five control subjects based on year of birth, sex, database listing (e.g., a patient from CPRD Aurum was matched with a control from CPRD Aurum), date of first appearance of a PK deficiency diagnosis code and registered general practice. Controls were defined (using MedCodes) as those who had no PK deficiency or other acquired or congenital anaemias and with at least one medical record of any type in the same calendar year as the first observed occurrence of a PK deficiency diagnosis code for their matched case.</p><p>For cases, the index date was defined as the date of the first observed occurrence of a PK deficiency diagnosis code. For controls, the index date was defined as the first available medical record within the same calendar year as the index date for their matched case. Clinical data, such as complications, were reported from the earliest available date in patients’ records. Patient demographics and clinical characteristics at the index date were ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530425","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":"Reticulin-Free Quantitation of Bone Marrow Fibrosis in MPNs: Utility and Applications","authors":"Hosuk Ryou,&nbsp;Emily Thomas,&nbsp;Marta Wojciechowska,&nbsp;Laura Harding,&nbsp;Ka Ho Tam,&nbsp;Ruoyu Wang,&nbsp;Xuezi Hu,&nbsp;Jens Rittscher,&nbsp;Rosalin Cooper,&nbsp;Daniel Royston","doi":"10.1002/jha2.70005","DOIUrl":"https://doi.org/10.1002/jha2.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Automated quantitation of marrow fibrosis promises to improve fibrosis assessment in myeloproliferative neoplasms (MPNs). However, analysis of reticulin-stained images is complicated by technical challenges within laboratories and variability between institutions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We have developed a machine learning model that can quantitatively assess fibrosis directly from H&amp;E-stained bone marrow trephine tissue sections.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our haematoxylin and eosin (H&amp;E)-based fibrosis quantitation model demonstrates comparable performance to an existing reticulin-stained model (Continuous Indexing of Fibrosis [CIF]) while benefitting from the improved tissue retention and staining characteristics of H&amp;E-stained sections.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>H&amp;E-derived quantitative marrow fibrosis has potential to augment routine practice and clinical trials while supporting the emerging field of spatial multi-omic analysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497287","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":"An Editorial Introduction: A Vision for eJHaem","authors":"Phillip Scheinberg","doi":"10.1002/jha2.70004","DOIUrl":"https://doi.org/10.1002/jha2.70004","url":null,"abstract":"&lt;p&gt;It is with a great sense of privilege that I assume the role of Editor-in-Chief of &lt;i&gt;eJHaem&lt;/i&gt;, the open-access journal of the British Society for Haematology (BSH). Established in 2020, &lt;i&gt;eJHaem&lt;/i&gt; is a relatively young journal that has already become an important publication within the BSH family of journals.&lt;/p&gt;&lt;p&gt;Since its inception, Dr. Andrew Evens has brilliantly led &lt;i&gt;eJHaem&lt;/i&gt;. Under his guidance, the Journal has published a wide variety of content, including original articles, short reports, case reports, letters, correspondence, and striking images in haematology. The journal covers all aspects of haematology—both benign and malignant diseases, adult and paediatrics—as well as topics in cell therapy (HSCT and CAR-T) and transfusion medicine.&lt;/p&gt;&lt;p&gt;As Editor-in-Chief, I aim to expand the journal's reach, ensuring it becomes a truly global venue representing physicians, scientists, and researchers from diverse regions. A bit about my background: I was born in Boston and raised in São Paulo, Brazil. I returned to the United States for medical training, where I spent 15 years completing my internship, residency, chief residency, and fellowships in both haematology and oncology. For over a decade, I worked at the Haematology Branch of the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) in Bethesda, Maryland. During my fellowships at the NIH, I conducted research both at the bench and in the clinic. After this period, I returned to São Paulo in 2012 to become the Head of the Division of Haematology at one of the largest cancer centres in the country. My international experience has impacted my vision for &lt;i&gt;eJHaem&lt;/i&gt;: to make it not only accessible but also truly “author-friendly” for contributors worldwide, while expanding its reach to less represented regions.&lt;/p&gt;&lt;p&gt;It is bittersweet to step down from my role as an Associate Editor (AE) of the &lt;i&gt;British Journal of Haematology&lt;/i&gt; (&lt;i&gt;BJHaem&lt;/i&gt;), where I have served since 2019. I am grateful for the warm welcome I received and for the opportunity to contribute to &lt;i&gt;BJHaem&lt;/i&gt;. I particularly want to thank Dr. John Barrett, Editor-in-Chief during my tenure. With his leadership, talent, and knowledge, John excelled at enhancing the quality and breadth of &lt;i&gt;BJHaem&lt;/i&gt;’s publications and assembling a truly top-notch team of Associate Editors. I would also like to express my gratitude to Lorna Wycherley, the journal's exceptional Editorial Assistant, whose efforts kept the editorial process running smoothly, and Claire Dowbekin, Wiley's senior publisher, for her openness to innovation, collaboration, and support.&lt;/p&gt;&lt;p&gt;As I take on this new role, I am excited to continue working alongside Dr. Andrew Evens, who is stepping into the role of Editor-in-Chief at &lt;i&gt;BJHaem&lt;/i&gt;. Andy has outlined a clear and inspiring vision for &lt;i&gt;BJHaem&lt;/i&gt;, which I fully endorse for &lt;i&gt;eJHaem&lt;/i&gt; [&lt;span&gt;1&lt;/span&gt;]. His directives include streamlining the edit","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489979","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":"CAR-T Cell Therapy for PTLD: Analysis of CAR-T Product, Engraftment, and Outcomes in Patients Receiving Parallel Immunosuppression","authors":"Aikaterini Panopoulou,&nbsp;Vedika Mehra,&nbsp;Kate Cwynarski,&nbsp;Andrew Morley-Smith,&nbsp;Angela Hwang,&nbsp;Maeve O'Reilly,&nbsp;Harriet Roddy,&nbsp;Claire Roddie","doi":"10.1002/jha2.70006","DOIUrl":"https://doi.org/10.1002/jha2.70006","url":null,"abstract":"&lt;p&gt;Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of solid organ transplantation (SOT) [&lt;span&gt;1&lt;/span&gt;]. Following FDA approval in large B-cell lymphoma (LBCL), PTLD patients can now access CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, but having been excluded from pivotal trials, there are limited clinical data on response/toxicity and peri-CAR-T immunosuppression (IS) management. Lifelong IS is critical to prevent organ rejection but may be detrimental to CAR-T function/expansion [&lt;span&gt;2&lt;/span&gt;] which may adversely impact clinical responses [&lt;span&gt;3, 4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Here, we describe third-line CD19CAR-T therapy with axicabtagene ciloleucel (axi-cel) in two PTLD patients who continued therapeutic IS throughout to protect graft function. In parallel, we performed CAR-T product and peripheral blood (PB) CAR-T marking analysis. Clinical and laboratory methods are detailed in Supporting Information appendix.&lt;/p&gt;&lt;p&gt;&lt;i&gt;Patient 1 (P1)&lt;/i&gt;: A 24-year-old male had received orthotopic cardiac transplant at 3 years of age for epstein barr virus (EBV)-related myocarditis and commenced lifelong tacrolimus/azathioprine. He developed EBV-negative monomorphic PTLD and received five lines of therapy for multiple relapse events prior to axi-cel referral (detailed in Table S1). Leukapheresis was performed without tacrolimus interruption. PB lymphocyte count was 0.72 × 10&lt;sup&gt;9&lt;/sup&gt;/L, CD3+ count was 0.68 × 10&lt;sup&gt;9&lt;/sup&gt;/L, and total harvested CD3+ yield was 2.64 × 10&lt;sup&gt;9&lt;/sup&gt;. Despite therapeutic tacrolimus, the product fulfilled manufacturing release criteria. Bridging comprised rituximab, bendamustine, and polatuzumab vedotin (RBP) to progressive disease (PD).&lt;/p&gt;&lt;p&gt;He received fludarabine/cyclophosphamide/CAR-T infusion and developed grade (G)1 CRS on day 1 (but no ICANS/graft rejection), receiving tocilizumab 8 mg/kg. Tacrolimus remained within the 5–7 ng/mL target range. Day 28 PET-CT showed complete metabolic response (CMR). Month 3 PET-CT showed a single avid para-aortic node, treated with 40 Gy radiotherapy to CMR, ongoing at month 12 (Figure S1a).&lt;/p&gt;&lt;p&gt;&lt;i&gt;Patient 2 (P2)&lt;/i&gt;: A 51-year-old male underwent cadaveric renal transplantation for polycystic kidney disease. He developed EBV+ monomorphic PTLD 2 months post-SOT which was refractory to six lines of treatment (detailed in Table S1). His latest line of therapy was one cycle of RBP, delivered 32 days prior to apheresis. IS comprised prednisolone monotherapy (20 mg/day). Pre-leukapheresis, his PB lymphocyte and CD3+ T-cell counts were 0.24 × 10&lt;sup&gt;9&lt;/sup&gt;/L and 0.11 × 10&lt;sup&gt;9&lt;/sup&gt;/L. His lymphocyte count had been consistently ≤0.3 × 10&lt;sup&gt;9&lt;/sup&gt;/L for &gt;1 year after steroids/prior therapies, and the total CD3+ T-cell yield from leukapheresis was 1.39 × 10&lt;sup&gt;9&lt;/sup&gt;. The resulting CAR-T product was out-of-specification (OOS) due to low cell viability (71% against a specification of ≥80%) but was approved for infusion d","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447201","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":"Paternal Split-Liver Transplantation Followed by Haploidentical Hematopoietic Cell Transplantation in an Adult Patient With Protoporphyria-Induced Liver Failure","authors":"Ulrich Stölzel,&nbsp;Lasse Jost,&nbsp;Daniel Seehofer,&nbsp;Katharina Egger-Heidrich,&nbsp;Uwe Scheuermann,&nbsp;Kristina Hölig,&nbsp;Thomas Stauch,&nbsp;Desiree Kunadt,&nbsp;Detlef Schuppan,&nbsp;Johannes Schetelig,&nbsp;Nils Wohmann,&nbsp;Martin Bornhäuser,&nbsp;Friedrich Stölzel","doi":"10.1002/jha2.1092","DOIUrl":"https://doi.org/10.1002/jha2.1092","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Erythropoietic Protoporphyria (EPP) caused skin light sensitivity and liver cirrhosis in a 35-year-old patient who subsequently developed liver-failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In absence of a human leukocyte antigens (HLA)-matched-unrelated donor, the father consented in donating for split liver transplantation (SLT) and allogeneic hematopoietic cell transplantation (HCT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After bridging therapy and successful SLT a first paternal HCT resulted in graft failure. For a second haploidentical HCT a different regimen was applied leading to engraftment while protoporphyrin (PP) blood-levels decreased to normal and skin light sensitivity skin disappeared, leading to complete remission in an immunosuppressive-free patient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Haploidentical transplantation is a feasible treatment approach in EPP-patients.</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 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431677","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":"Acute myeloid leukemia with RAM immunophenotype: A report of three patients and comprehensive literature review","authors":"Xenia Parisi,&nbsp;Anindita Ghosh,&nbsp;L. Jeffrey Medeiros","doi":"10.1002/jha2.1074","DOIUrl":"https://doi.org/10.1002/jha2.1074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The RAM immunophenotype (IP) in acute myeloid leukemia (AML) is defined by blasts with bright CD56 and weak-to-negative CD45, HLA-DR, and CD38 expression. A RAM IP predominantly presents in infants who have “standard-risk disease” under current criteria but, when treated accordingly, have devastatingly high rates of minimal residual disease and relapse with lower 3-year and overall survival rates. However, given the relative rarity of this phenotype, it is neither well-defined nor readily diagnosed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We reviewed the electronic medical records of our institution from 1990 to 2024 for cases of AML expressing bright CD56 on flow cytometry and identified three cases with a RAM IP. Further, we performed a thorough literature search and reviewed impactful studies on pediatric AML and case/series reports of patients with a RAM IP, leading to the identification of 38 more cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 41 patients were collected. These patients were toddler age (1–3 years) with an equal sex distribution and clinically presented with low circulating blasts and cytopenias. Blasts were typically French–American–British M0 or M7. Immunophenotypically, CD33 and CD117 showed positivity in &gt;90% of cases, with CD19, CD34, CD41, and CD42b, frequently positive. Half of the cases were positive for CD7 and CD61. T-cell/myeloid markers were rare, except for cytoplasmic CD3, seen in 1/3, apparently correlating with <i>CBFAT2T3:GLIS1</i> fusions. Gains in chromosomes 21, 13, and 8 and <i>CBFAT2T3::GLIS1</i> fusions were frequent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AML with a RAM IP has a poor prognosis. This study offers a detailed characterization of the clinicopathologic patterns associated with this rare entity, which may help formulate the most appropriate diagnostic approach.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389083","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":"Hodgkin Lymphoma Treatment With Brentuximab Vedotin in a Patient With HIV, Liver Failure, and Anemia Without Transfusion","authors":"Ellen Marin,&nbsp;Aseala Abousaud,&nbsp;Kathleen Davis,&nbsp;Bradley Sumrall,&nbsp;Shiyong Li,&nbsp;Amelia A. Langston,&nbsp;Andres Chang","doi":"10.1002/jha2.70001","DOIUrl":"https://doi.org/10.1002/jha2.70001","url":null,"abstract":"<p>Brentuximab vedotin (BV) is a drug that has improved outcomes in classical Hodgkin lymphoma (cHL). However, its safety and efficacy in patients living with HIV who present with severe liver failure and life-threating cytopenias is unclear. Here, we describe the case of a woman living with HIV diagnosed with cHL and how she recovered from a hemoglobin nadir of 24 g/L despite declining transfusion support and a bilirubin peak of 417.24 µmol/L, eventually achieving a complete response with a BV-based therapy. Studies are needed to determine the safety and efficacy of BV in patients excluded from the pivotal trials.</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 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388962","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":"Treatment of Myeloproliferative Neoplasms With Janus Kinase Inhibitors: A Meta-Analysis of Cardiovascular Safety","authors":"Roberta Dunn,&nbsp;Edouard Long,&nbsp;Laura Li Gagnon,&nbsp;Claire Harrison,&nbsp;Yunfan Yang,&nbsp;Jennifer O'Sullivan","doi":"10.1002/jha2.70000","DOIUrl":"https://doi.org/10.1002/jha2.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Janus kinase inhibitors (JAKis) are an integral aspect of the management of myeloproliferative neoplasms (MPNs). Part of the clinical benefit derived from JAKis may be due to reductions in thrombosis, a potentially life-threatening complication of MPNs. However, evidence has emerged of adverse cardiovascular effects secondary to JAKis. We conducted a first-of-a-kind meta-analysis of the cardiovascular safety of JAKis in the treatment of MPNs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Systematic searches for studies comparing JAKi treatment to a control group were conducted. Studies reporting hypertension, major adverse cardiovascular events (MACE) and thromboembolic events were included in a meta-analysis using a random-effects model for the primary analysis, and fixed-effects model for any subgroup analyses performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 23 publications, consisting of nine clinical trials and one retrospective analysis, met the inclusion criteria. This resulted in a pooled population of 2198 patients (JAKi <i>n</i> = 1145, Control <i>n</i> = 1053). In studies reporting thromboembolic events (<i>n</i> = 9), pooled analysis revealed a significantly lower rate of thromboembolic events in the JAKi group (incidence rate ratio (IRR): 0.52, 95% CI: 0.28–0.98, <i>p</i> = 0.04). This was primarily driven by ruxolitinib studies in myelofibrosis (MF) and polycythemia vera (PV) as when a subgroup analysis of these trials was performed (<i>n</i> = 7), an even more significant reduction in thromboembolic events with JAKi treatment was found (IRR: 0.41, 95%CI: 0.26–0.64, <i>p</i> &lt; 0.001). There was no significant difference in MACE or hypertension between JAKi and control groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This meta-analysis suggests that JAKi treatment of MPN was associated with a reduced risk of thromboembolic events; primarily driven by studies of ruxolitinib in PV and MF. Further prospective clinical trials are warranted to confirm these findings and characterise the cardiovascular profile of other JAKis and other types of MPNs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389030","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":"An Economic Evaluation of the TROG 99.03 Trial: Systemic Therapy After Radiotherapy in Early-Stage Follicular Lymphoma","authors":"Daniel Erku,&nbsp;Joshua W. D. Tobin,&nbsp;John F. Seymour,&nbsp;Michael MacManus,&nbsp;Paul Scuffham,&nbsp;Greg Hapgood","doi":"10.1002/jha2.70002","DOIUrl":"https://doi.org/10.1002/jha2.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The TROG 99.03 trial demonstrated improved progression-free survival for patients with early-stage follicular lymphoma (FL) treated with systemic therapy using rituximab-cyclophosphamide, vincristine, prednisolone (R-CVP) after involved-field radiotherapy (RT) versus RT. As systemic therapy was associated with more acute toxicity, the possibility of long-term toxicity, and no survival benefit yet, the cost-effectiveness of RT+R-CVP is important.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We performed a cost-effectiveness analysis of RT (reference), RT+CVP, and RT+R-CVP from the TROG 99.03 trial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We constructed a Markov model (15-year horizon) to compare treatments: RT (reference), RT+CVP and RT+R-CVP from the 150 patients in the TROG 99.03 trial. Median follow-up was 11.3 years (range: 4.4–17.8). Lifetime direct health care costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. Australian dollars AUD$50,000 was defined as the proposed willingness-to-pay threshold (WTP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RT+R-CVP was associated with an improvement of 0.711 QALYs compared to RT, 0.532 QALYs compared to RT+CVP, and was the dominant strategy. The costs of adverse events or retreatment for relapses or transformation had a minimal influence on the ICERs. Sensitivity analyses resulted in ICER values below the WTP with RT+R-CVP remaining the dominant strategy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>RT+R-CVP is clearly cost-effective and was the dominant strategy in early-stage FL compared to RT or RT+CVP as it delivers superior outcomes at a lower cost from the Australian tax-payer's perspective.</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 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389084","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":"Therapeutic Versus Non-Therapeutic Dose Anticoagulation in COVID-19 Infection: A Systematic Review and Meta-analysis of Randomised Controlled Trials","authors":"Sushil Selvarajan,&nbsp;Jisha Sara John,&nbsp;Prathap Tharyan,&nbsp;Richard Kirubakaran,&nbsp;Bhagteshwar Singh,&nbsp;Biju George,&nbsp;Joseph L. Mathew,&nbsp;Priscilla Rupali","doi":"10.1002/jha2.1100","DOIUrl":"https://doi.org/10.1002/jha2.1100","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Abnormal coagulation and thrombotic complications prompted many guidelines to recommend thromboprophylaxis for patients hospitalised with COVID-19, but the dose required for prophylaxis remains unclear. This systematic review (SR) analyses the safety and efficacy of therapeutic dose anticoagulation (TDA) versus non-therapeutic dose anticoagulation (NDA) in COVID-19 patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>According to the <i>Cochrane Handbook of Systematic Review of Interventions</i>, we performed an SR. The protocol is registered in Prospero (CRD42021269197, date 12 August 2021).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this SR of 18 studies, TDA was shown to reduce all-cause mortality (risk ratio [RR] 0.83; 95% confidence interval [95% CI] 0.70, 0.99) in COVID-19 infection. TDA also reduced thrombosis (RR 0.55; 95% CI 0.48, 0.72) but increased major bleeding (RR 1.87; 95% CI 1.29, 2.69). A stratified analysis according to severity revealed that, in non-critical patients, TDA resulted in mortality benefit (RR 0.79; 95% CI 0.67, 0.94). In critical patients, TDA did not affect all-cause mortality (RR 1.03; 95% CI 0.89, 1.18) but reduced thrombosis (RR 0.65; 95% CI 0.48, 0.86) and increased major bleeding (RR 1.85; 95% CI 1.06, 3.23).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TDA significantly reduced all-cause mortality and thrombosis in non-critical COVID-19 patients at the expense of increased major bleeding. In critical COVID-19, this mortality benefit was not observed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380721","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}