EJHaem最新文献

{"title":"Early Free Light-Chain Suppression as a Prognostic Marker in Relapsed and Refractory Myeloma Patients Treated With BCMA-Directed CAR-T Cells","authors":"Tim Richardson,&nbsp;Hishan Tharmaseelan,&nbsp;Guido Kobbe,&nbsp;Ben-Niklas Baermann,&nbsp;Tobias A. W. Holderried,&nbsp;Friederike Schmitz,&nbsp;Martina Crysandt,&nbsp;Philipp Gödel,&nbsp;Nathan Wolfensberger,&nbsp;Daniel Schütte,&nbsp;Michael Hallek,&nbsp;Christof Scheid,&nbsp;Udo Holtick","doi":"10.1002/jha2.70139","DOIUrl":"https://doi.org/10.1002/jha2.70139","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Relapsed/refractory multiple myeloma (RRMM) remains difficult to treat despite advances in therapy. B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapies, such as idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have improved outcomes, yet many patients relapse within a year. Current International Myeloma Working Group (IMWG) criteria for deep response require prolonged observation. Early, practical biomarkers could enable timelier risk stratification and intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate whether serum free light-chain (FLC) suppression at Day +28 after BCMA-directed CAR-T infusion predicts progression-free survival (PFS) and overall survival (OS) in RRMM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective multicenter analysis of 80 consecutive RRMM patients treated with in-label ide-cel or cilta-cel between January 2022 and July 2024 at four tertiary centers. Patients with oligo-/non-secretory myeloma were excluded. FLC suppression—defined as undetectable <i>κ</i> or <i>λ</i> light chains using the Freelite assay—was assessed at Day +28 (window: Days 27–31) and at 3 months post-infusion. Survival analyses used a landmark approach from Day +28. Multivariate Cox regression adjusted for prior BCMA/T-cell-directed therapy, high-risk cytogenetics (HRC), extramedullary disease (EMD), and pre-CAR-T response status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At Day +28, 51 patients (63.8%) achieved FLC suppression. Median follow-up was 11.8 months. FLC suppression correlated with markedly longer median PFS (23.4 vs. 4.1 months, <i>p</i> &lt; 0.001) and improved OS (12-month OS: 88.0% vs. 18.1%, <i>p</i> = 0.013). Benefits were observed across CAR-T products, but suppression rates were higher with cilta-cel (81.6%) than ide-cel (45.2%). HRC remained an adverse factor even in suppressed patients, while EMD showed a less consistent effect. In multivariate analysis, absence of FLC suppression independently predicted inferior PFS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FLC suppression at Day +28 post-CAR-T is an early, inexpensive biomarker associated with superior PFS and OS in RRMM. It often precedes IMWG-defined complete response and could support risk-adapted post-CAR-T management. Prospective validation is warranted to integrate FLC suppression into early response assessment","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 5","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918685","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":"Chemokine Receptor Profiles as Predictors of Survival and Early Progression in Follicular Lymphoma","authors":"Antonella Zupo,&nbsp;Katrin Pansy,&nbsp;Lukas Gaksch,&nbsp;Julia Waldhart,&nbsp;Andrea Brunner,&nbsp;Johanna Strobl,&nbsp;Marta Szmyra-Polomka,&nbsp;Sandra Haingartner,&nbsp;Peter V. Tomazic,&nbsp;Hildegard T. Greinix,&nbsp;Barbara Uhl,&nbsp;Julia Feichtinger,&nbsp;Georg Stary,&nbsp;Johannes Haybaeck,&nbsp;Fotini Rosi Vagena,&nbsp;Martin Zacharias,&nbsp;Christine Beham-Schmid,&nbsp;Peter Neumeister,&nbsp;Katharina Theresa Prochazka,&nbsp;Alexander J. A. Deutsch","doi":"10.1002/jha2.70131","DOIUrl":"https://doi.org/10.1002/jha2.70131","url":null,"abstract":"<p><b>Objective</b>: Classical follicular lymphoma (FL) is a heterogeneous malignancy. Early progression within 24 months (POD24) is linked to poor outcomes. However, precise risk stratification remains unclear. We aimed to explore chemokine receptor (CR) expression profiles as potential markers of disease biology and outcome in FL.</p><p><b>Methods</b>: We analyzed mRNA expression of <i>CCR1–CCR10</i>, <i>CXCR1</i>–<i>CXCR5</i>, <i>CX3CR1</i>, and <i>XCR1</i> in 52 FL samples (13 POD24, 39 non-POD24) using RT-qPCR. Immunohistochemistry for CCR3, CCR7, CXCR3, CXCR4, and CXCR5 was performed. Reactive tonsils (<i>n</i> = 5) served as controls.</p><p><b>Results</b>: Compared to controls, FL samples showed lower <i>CCR1</i>, <i>CCR6</i>, <i>CCR7</i>, <i>CXCR1</i>, <i>CXCR5</i>, and <i>CX3CR1</i> but higher <i>CCR4</i>, <i>CCR5</i>, <i>CCR8</i>, and <i>CCR9</i> expression. Grade 3a FL correlated with reduced <i>CCR8</i>, <i>CXCR1</i>, and <i>CXCR3</i>, and increased <i>CCR7</i>. POD24 cases had elevated <i>CCR3</i>, <i>CCR4</i>, CCR7, <i>CXCR4</i>, and <i>XCR1</i> but reduced <i>CXCR3</i>. High <i>CCR3</i>, <i>CCR4</i>, and <i>CCR10</i> levels were linked to inferior survival. Cluster analysis revealed two CR-based subgroups; most POD24 cases clustered in the group with worse prognosis.</p><p><b>Conclusion</b>: These findings suggest distinct chemokine receptor expression profiles contribute to FL progression. Our data highlight several CRs as candidate prognostic markers and potential therapeutic targets in the context of POD24, warranting further investigation in larger, prospective cohorts.</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 5","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915118","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":"First Report of MPL c.23T>G (p.M8R) Variant in Congenital Amegakaryocytic Thrombocytopenia: A Case Report","authors":"Atbin Latifi,&nbsp;Sina Yousefian","doi":"10.1002/jha2.70136","DOIUrl":"https://doi.org/10.1002/jha2.70136","url":null,"abstract":"<p>Congenital amegakaryocytic thrombocytopenia is a rare inherited bone marrow failure syndrome primarily caused by MPL gene mutations. It presents with severe neonatal thrombocytopenia and typically progresses to pancytopenia. We report the first disease-associated case of the MPL variant c.23T&gt;G, identified through whole-exome sequencing in an infant diagnosed with congenital amegakaryocytic thrombocytopenia. Based on ACMG criteria, we propose classification of the MPL c.23T&gt;G (p.M8R) variant as likely pathogenic. This case highlights the importance of early genetic testing in infants with unexplained thrombocytopenia and emphasizes the need to distinguish congenital amegakaryocytic thrombocytopenia from other inherited bone marrow failure syndromes.</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 5","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915109","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":"Alpha-Globin Gene Triplication in Central Thailand: Prevalence, Haematological Findings and Clinical Impact With Co-Inherited Beta-Globin Mutations","authors":"Boonyanuch Dujjawan,&nbsp;Yingyong Chinthammitr,&nbsp;Theera Ruchutrakool,&nbsp;Chattree Hantaweepant","doi":"10.1002/jha2.70128","DOIUrl":"https://doi.org/10.1002/jha2.70128","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We aimed to ascertain the prevalence of ααα^anti-3.7 and ααα^anti-4.2 triplications in central Thailand and to characterise the phenotypes of individuals harbouring these variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We performed a retrospective review of adult (≥ 18 years) samples submitted for polymerase chain reaction-based α-globin mutation analysis at Siriraj Hospital, Mahidol University, Bangkok (January 2012–December 2021). Haematological indices were compared between carriers and non-carriers of α-globin triplications, and clinical severity was assessed in those with co-inherited β-globin mutations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1559 subjects, α-globin triplication prevalence was 1.28%, with ααα^anti-4.2 (0.83%) more frequent than ααα^anti-3.7 (0.45%). Double heterozygosity for an α triplication and a β-globin mutation occurred in 0.9%. Individuals carrying ααα^anti-3.7 or ααα^anti-4.2 had lower mean haemoglobin levels (10.00 and 11.23 ± 1.85 g/dL, respectively) than those without triplication (12.35 ± 2.59 g/dL). Among heterozygous β-thalassaemia individuals, co-inheritance of ααα^anti-3.7 or ααα^anti-4.2 was associated with significantly reduced mean haemoglobin (8.38 ± 1.58 and 8.28 ± 1.15 g/dL, respectively). This contrasts with the non-triplication group (11.14 ± 1.86 g/dL). Of 14 subjects with double heterozygosity, 8 had thalassaemia intermedia and 6 had thalassaemia trait.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although uncommon in central Thailand, α-globin triplications can exacerbate anaemia in individuals with co-inherited heterozygous β-globin mutations, supporting routine screening in symptomatic cases.</p>\u0000 \u0000 <p><b>Trial Registration</b>: 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 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905648","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":"Foamy Macrophages and Blue Histiocytes as Diagnostic Clues to Acid Sphingomyelinase Deficiency","authors":"Andrea Franch,&nbsp;Mònica Ribell Bachs,&nbsp;Jose Ramón Álamo Moreno","doi":"10.1002/jha2.70098","DOIUrl":"https://doi.org/10.1002/jha2.70098","url":null,"abstract":"<p>We report the case of a 54-year-old Spanish male, born to consanguineous parents, with no relevant medical history, who presented with progressive interstitial lung disease, hepatosplenomegaly with portal hypertension, and pruritic cutaneous lesions. Laboratory tests revealed microcytic anaemia (haemoglobin 89 g/L, MCV 79 fL) and thrombocytopenia (platelets 93 ×10⁹/L), with a normal white blood cell count. Viral hepatitis and full autoimmune screenings were negative except for an elevated angiotensin-converting enzyme (ACE), low-titre positive anti-nuclear antibodies (ANA), and polyclonal hypergammaglobulinaemia. Whole-body CT scan showed splenic lesions and paravertebral masses.</p><p>Differential diagnoses included systemic autoimmune conditions, connective tissue disorders, sarcoidosis, infections (e.g., <i>Leishmania</i>, tuberculosis), and haematological malignancies, such as lymphoproliferative or myeloproliferative disorders.</p><p>The peripheral blood smear showed no abnormalities. Bone marrow aspirate was markedly hypercellular, with preserved trilineage haematopoiesis, reversed myeloid–erythroid ratio, and mild dyserythropoiesis (14%). Strikingly, numerous scattered foamy macrophages coexisted with characteristic blue histiocytes—displaying deeply basophilic cytoplasm on May–Grünwald Giemsa stain (Figures 1 and 2).</p><p>Although blue histiocytes may appear as reactive findings in diverse contexts, the absence of features supporting haematologic malignancy led to targeted evaluation for inherited lysosomal storage disorders. Enzymatic testing revealed deficient acid sphingomyelinase activity, and molecular analysis confirmed acid sphingomyelinase deficiency (ASMD, formerly Niemann–Pick disease type B), due to a homozygous c.96G&gt;A (p.Trp32*) nonsense mutation in the <i>SMPD1</i> gene, resulting in early termination of the protein. The patient initiated enzyme replacement therapy with olipudase alfa in May 2025, administered intravenously every 2 weeks with gradual dose escalation.</p><p>ASMD is a rare autosomal recessive disorder caused by lysosomal dysfunction, with organ infiltration due to lipid accumulation. Although three clinical forms are described, type B can manifest in adulthood and often evades early detection, frequently delaying diagnosis—as was the case in our patient.</p><p>This case underscores the diagnostic value of bone marrow morphology in patients with cytopenias and systemic findings. The concurrent presence of foamy macrophages and blue histiocytes should raise suspicion for lipid storage diseases, particularly ASMD, and prompt timely metabolic and genetic investigations to establish a final diagnosis and start early treatment.</p><p>All authors have contributed equally to the study.</p><p>This manuscript respects the ethical policy of our centre for the treatment of human research participants.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905647","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":"Evaluating Economic and Clinical Impacts of Anaemia Management Strategies: A Systematic Review of the Evidence From the UK Perspective","authors":"Hiro Farabi,&nbsp;Florian Tomini,&nbsp;Hayley Evans,&nbsp;Michael F. Murphy,&nbsp;Laura Green,&nbsp;Paula Dhiman,&nbsp;Gianluca Fabiano,&nbsp;Antony J. R. Palmer,&nbsp;Linda von Neree,&nbsp;Simon J. Stanworth","doi":"10.1002/jha2.70124","DOIUrl":"https://doi.org/10.1002/jha2.70124","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Anaemia significantly affects health outcomes and quality of life. While blood transfusion remains a common intervention, alternative treatments, such as iron supplementation and erythropoiesis-stimulating agents (ESAs), offer potential to mitigate transfusion-associated costs. However, robust evidence on their cost-effectiveness remains limited.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This review assesses the cost-effectiveness of anaemia treatments, aiming to inform UK healthcare policy and practice.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A systematic review was conducted following PRISMA guidelines, identifying economic evaluations published between 2015 and 2025. Study quality was appraised using the Drummond checklist and NICE reference case criteria. Data were synthesised using the Hierarchical Decision Matrix framework.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Of 5496 records screened, 14 studies met inclusion criteria; 11 were included in the final synthesis, with three excluded due to low methodological quality. Restrictive transfusion strategies were cost-saving (£35.50–£75 per patient), reduced red blood cell utilisation by ∼21%, shortened length of stay by 0.5 to 3 days, and yielded modest QALY gains (0.01 to 0.02). ESAs reduced transfusion risk (RR 0.61 to 0.87) but incurred substantial incremental costs (£1859–£3060) with limited evidence of QALY gains. Transfusion of fresher blood in ICU settings increased costs without a measurable clinical or economic advantage. Preoperative erythropoietin and ferric carboxymaltose reduced transfusion incidence but were high-cost interventions with limited evidence on QALY gains. Patient Blood Management (PBM), particularly intravenous iron, was cost-saving (£30.80–1166 saved per patient), reduced transfusion rates (RR 0.61), but with limited evidence on QALY gains.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Restrictive transfusion thresholds and PBM interventions, especially intravenous iron, demonstrate favourable cost-effectiveness and potential for NHS cost savings. In contrast, the cost-effectiveness of ESAs remains uncertain due to high costs and limited utility evidence. Further research is needed to capture long-term outcomes and generate UK-specific economic data.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Trial Registration&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897639","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":"Dual Assessment of the RBC Fraction Abnormally Retaining Mitochondria and of the RBC Mitochondrial Load Provides a New Clinical Parameter for Sickle Cell Disease Patients","authors":"Eric Soupene,&nbsp;Hart Horneman,&nbsp;Mikail Alejandro,&nbsp;Kenzy Mohammed,&nbsp;Yaw Ofosu Nyansa Ansong-Ansongton,&nbsp;Angela Rivers","doi":"10.1002/jha2.70130","DOIUrl":"https://doi.org/10.1002/jha2.70130","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Mitochondria and other organelles are normally eliminated in a process called mitophagy during the maturation of hematopoietic precursors, leading to the release of enucleated red blood cells (RBCs) in circulation. In sickle cell disease (SCD), a significant fraction of the RBCs of patients abnormally retain mitochondria. This process increases the oxygen consumption rate and formation of reactive oxygen species, augmenting known pathways of hemolysis and playing a significant role in SCD pathophysiology. The retention of mitochondria in RBC is detectable by flow cytometry analysis of whole blood, but this approach does not quantify the number of mitochondria in individual cells.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Mitochondrial DNA was isolated from sorted RBC (10&lt;sup&gt;6&lt;/sup&gt; cells) of a cohort of pediatric sickle patients (HbSS, &lt;i&gt;n&lt;/i&gt; = 19; HbSC/HbSE, &lt;i&gt;n&lt;/i&gt; = 8) and quantified by qPCR with a standard curve.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The methodology is suitable for the clinical quantification of the severity of mitochondrial retention in RBC of individuals with SCD. The number of mitochondria in RBCs are obtained from quantification of the copy numbers of mtDNA &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;(&lt;/mo&gt;\u0000 &lt;mi&gt;H&lt;/mi&gt;\u0000 &lt;mi&gt;b&lt;/mi&gt;\u0000 &lt;mi&gt;S&lt;/mi&gt;\u0000 &lt;mi&gt;S&lt;/mi&gt;\u0000 &lt;mo&gt;,&lt;/mo&gt;\u0000 &lt;mspace&gt;&lt;/mspace&gt;\u0000 &lt;mover&gt;\u0000 &lt;mi&gt;x&lt;/mi&gt;\u0000 &lt;mo&gt;¯&lt;/mo&gt;\u0000 &lt;/mover&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$(HbSS, bar{x}$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;= 21 copies/total RBC) and the mitochondria positive RBCs fraction is determined by flow cytometry (&lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mi&gt;H&lt;/mi&gt;\u0000 &lt;mi&gt;b&lt;/mi&gt;\u0000 &lt;mi&gt;S&lt;/mi&gt;\u0000 &lt;mi&gt;S&lt;/mi&gt;\u0000 &lt;mo&gt;,&lt;/mo&gt;\u0000 &lt;mspace&gt;&lt;/mspace&gt;\u0000 &lt;mover&gt;\u0000 &lt;mi&gt;x&lt;/mi&gt;\u0000 &lt;mo&gt;¯&lt;/mo&gt;\u0000 &lt;/mover&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$HbSS, bar{x}$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;= 11%), which provides the number of mitochondria present in the population of RBCs ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897505","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 Unusual Cause of Hexokinase 1 Deficiency—Case Report","authors":"Gonench Kilich,&nbsp;Kelly Maurer,&nbsp;Tanaya Jadhav,&nbsp;Tejas Jammihal,&nbsp;Zhe Zhang,&nbsp;Helge Hartung,&nbsp;Kosuki Izumi,&nbsp;Kelly Hassey,&nbsp;Anna Raper,&nbsp;Erica Schindewolf,&nbsp;Laura Conlin,&nbsp;Rebecca Ganetzky,&nbsp;Marilyn Li,&nbsp;Bertil Glader,&nbsp;Ramakrishnan Rajagopalan,&nbsp;Kathleen E. Sullivan","doi":"10.1002/jha2.70123","DOIUrl":"https://doi.org/10.1002/jha2.70123","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Molecular analysis of red cell disorders has revolutionized diagnosis, however, there remain challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Symptoms</h3>\u0000 \u0000 <p>This patient presented with hemolytic anemia in the newborn period. He required chronic transfusions to maintain his hemoglobin level until 6 years of age. A splenectomy was performed at 3 years of age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Diagnoses</h3>\u0000 \u0000 <p>Using whole genome sequencing, we were able to identify a duplication upstream of the red cell promoter of <i>HK1</i>. Long-read RNA sequencing established aberrant expression off of this promoter.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These non-coding variants remain challenging to identify. His promoter duplication may have a founder effect in South Asia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891733","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":"CD34 and HLA-DR Double Positive Microgranular Acute Promyelocytic Leukaemia With Multiple T- and B-Cell Markers Expression","authors":"Ke Xu,&nbsp;Evan Vitsaras,&nbsp;Rajeev Gupta","doi":"10.1002/jha2.70106","DOIUrl":"https://doi.org/10.1002/jha2.70106","url":null,"abstract":"<p>A 39-year-old male presented with fatigue. Bloodwork showed haemoglobin 53 g/L, white blood cell 2.3 × 10⁹/L, platelets 24 × 10⁹/L, and slightly deranged clotting screen (fibrinogen 2.7 g/L, PT 15 s, APTT 30 s). A bone marrow aspirate was effaced by blasts with blebbed basophilic cytoplasm and occasional Auer rods (Figure 1A). Multi-parameter flow cytometry showed the blasts were positive for CD34, HLA-DR, CD117, CD33, CD13, CD19, CD2, CD5, CD7, CD56, and myeloperoxidase, and negative for cCD3 and terminal deoxynucleotidyl transferase (Figure 1B). About 20% of blasts were CD38 negative, suggesting immaturity, which predicted adverse genetic risk. However, rapid combined exome/RNA sequencing (Oncomine Myeloid Assay GX v2) identified a <i>PML::RARA</i> bcr1 fusion, confirmed by fluorescence in situ hybridisation, with no other abnormalities. Acute promyelocytic leukaemia (APL) was diagnosed. With low white cell count and mild coagulopathy, this case was classified as standard risk APL. The patient received all-trans retinoic acid (ATRA) and arsenic trioxide with an uncomplicated course to complete molecular remission.</p><p>APL is a medical emergency. Microgranular APL can display atypical morphology and immunophenotype, which makes the diagnosis challenging [<span>1</span>]. This patient's immunophenotype is highly atypical but does not meet World Health Organization criteria for mixed-phenotype acute leukaemia [<span>1</span>]. ATRA is normally given to patients with suspected APL ahead of formal molecular diagnosis. Because of the atypical morphology and CD34+HLADR+ surface phenotype, APL was not initially suspected in this case. We recommend routine rapid testing for common fusions in newly diagnosed acute leukaemia to ensure correct classification and timely treatment.</p><p>K.X. wrote up the manuscript. E.V. and R.G. performed flow cytometry analysis. K.X., E.V., and R.G. critically revised the final version of the manuscript.</p><p>The authors declare no conflicts of interest.</p><p>This article does not contain any studies with human participants performed by any of the authors.</p><p>The authors have confirmed clinical trial registration is not needed for this submission.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888428","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":"Hemoglobin and High-Density Lipoprotein as Biomarker of Left Atrial Dilatation in Sickle Cell Disease","authors":"Guillaume Feugray,&nbsp;Maximilien Grall,&nbsp;Baptiste Gillardin,&nbsp;Julie Burdeau,&nbsp;Nicolas Ozanne,&nbsp;Cécile Dumesnil,&nbsp;Charles Fauvel,&nbsp;Paul Billoir","doi":"10.1002/jha2.70135","DOIUrl":"https://doi.org/10.1002/jha2.70135","url":null,"abstract":"<p>Sickle cell disease (SCD) is associated with cardiac remodeling, particularly left atrial dilatation, which may predict adverse cardiovascular outcomes. This study assessed cardiac abnormalities using echocardiography in 59 adult SCD patients and explored biomarkers predictive of left atrial remodeling. Left atrial dilatation was found in 61% of patients and significantly associated with hemoglobin, hemoglobin S, HDL-C, and the atherogenic index of plasma. An algorithm combining hemoglobin ≤ 9.7 g/dL and HDL-C ≤ 50 mg/dL showed high-diagnostic performance. These findings support biomarker-based screening as a useful tool in resource-limited settings for early detection of cardiac complications in SCD.</p><p><b>Trial Registration</b>: ClinicalTrials.gov identifier: NCT05376046</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888413","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}