EJHaem最新文献

{"title":"Acute myeloid leukemia presenting with hepatic dysfunction: Should induction be dose reduced?","authors":"Satish Maharaj,&nbsp;Simone Chang","doi":"10.1002/jha2.979","DOIUrl":"https://doi.org/10.1002/jha2.979","url":null,"abstract":"<p>The combination of de novo hepatic dysfunction and AML in a medically fit patient presents an unusual predicament. Cases present with obstructive jaundice and imaging typically shows diffuse hepatosplenomegaly, with some cases visualizing myeloid sarcomas causing biliary ductal dilatation. Guidelines for use of anthracyclines in hepatic dysfunction recommend dose reduction based on bilirubin blood levels, either to 50% or even omitting anthracycline. Randomized data however has shown that reduction of anthracycline in AML induction decreases overall survival and lowers remission rate. This case suggests, along withthe literature reviewed, that some medically fit patients with hepatic dysfunction benefit from and tolerate intensive induction therapy well without toxicity.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1092-1095"},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.979","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439030","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":"Real-world outcomes of patients with relapsed/refractory large B-cell lymphoma receiving second-line therapy in England","authors":"Christopher P. Fox,&nbsp;William Townsend,&nbsp;John G. Gribben,&nbsp;Tobias Menne,&nbsp;Nagesh Kalakonda,&nbsp;Paula Williams,&nbsp;Farah Toron,&nbsp;Emma Tyas,&nbsp;Miranda Cooper,&nbsp;Joshua Rickards,&nbsp;John Radford","doi":"10.1002/jha2.970","DOIUrl":"https://doi.org/10.1002/jha2.970","url":null,"abstract":"<p>Autologous stem-cell transplantation (ASCT) is standard therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL), but many patients are either ineligible or unable to receive it. This retrospective study characterized outcomes in R/R LBCL, delineated by eligibility for, and receipt of, ASCT. Median progression-free survival (PFS) and event-free survival (EFS) for patients undergoing ASCT were 35.2 and 31.6 months (overall survival [OS] not reached). Median PFS, EFS, and OS were 4.3, 4.3, and 6.9 months for ineligible patients, and 2.7, 2.6, and 9.4 months for those eligible for but unable to receive ASCT. This highlights an unmet need for alternative therapies in patients unable to receive ASCT.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"992-997"},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.970","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439029","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":"Selinexor in combination with dexamethasone with or without bortezomib in heavily pretreated multiple myeloma: A case series","authors":"Nini Aung,&nbsp;Margaret Bowers,&nbsp;Gillian Brearton,&nbsp;Andrew Charlton,&nbsp;Joanne Craig,&nbsp;Jonathan Cullis,&nbsp;Ray Dang,&nbsp;David Donaldson,&nbsp;Mary Drake,&nbsp;Rachel Hall,&nbsp;Elizabeth Parkins,&nbsp;Jane Tighe,&nbsp;Ceri Bygrave,&nbsp;Oonagh Sheehy","doi":"10.1002/jha2.913","DOIUrl":"https://doi.org/10.1002/jha2.913","url":null,"abstract":"<p>This report describes the characteristics and outcomes of 18 heavily pretreated patients with multiple myeloma (MM) who were subsequently treated with selinexor. This is a case series of 18 patients with MM who were treated with selinexor and dexamethasone (Sd) or selinexor, bortezomib, and dexamethasone (SVd) in 12 hospitals in the UK between 2019 and 2021. Eight patients received Sd and 10 patients received SVd. Patients received a median of five prior treatment lines, including immunomodulatory agents in 94% and proteasome inhibitors in 94%. Ten patients (55%) had triple-class refractory disease. Six of the 12 evaluable patients achieved ≥partial response. The median progression-free survival was 5.6 months, which was higher with SVd (5.7 months) than with Sd (2.1 months). The results support a treatment benefit of selinexor in heavily pretreated patients and support the notion that selinexor may overcome resistance to prior therapies, with no new safety concerns arising.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"987-991"},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.913","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439063","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":"Prevalence of metabolic syndrome in sickle cell disease patients: A cross-sectional study at a tertiary hospital in Nepal","authors":"Ramesh Khadayat,&nbsp;Mukesh Bishwakarma,&nbsp;Shubham Pant,&nbsp;Om Prakash Bhatta,&nbsp;Pariwesh Raj Bista,&nbsp;Sher Bahadur Kamar","doi":"10.1002/jha2.989","DOIUrl":"https://doi.org/10.1002/jha2.989","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;Sickle cell disease (SCD) is the most common hemoglobinopathy caused by an autosomal recessive genetic disorder leading to increased morbidity and mortality rates. SCD is prevalent in the Tharu community in the lowland (Terai) region of Nepal. Prevalence of metabolic syndrome among adults with SCD is poorly studied.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methodology&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This prospective cross-sectional study was conducted at Seti Provincial Hospital in Dhangadhi, Nepal, among 140 adolescents and adults with SCD, aged 15–60 years. Anthropometric and laboratory data were collected using an assisted questionnaire, and the SPSS software version 23 was used for data analysis. Descriptive and inferential statistics were used to summarize the presence of metabolic syndrome and were stratified in separate analyses by age and sex. National Cholesterol Education Program-Adult Treatment Panel III criteria were used to define metabolic syndrome.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aim&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This cross-sectional study aimed to assess the prevalence of metabolic syndrome among SCD patients with SCD registered at the Seti Provincial Hospital in Dhangadhi, Nepal.&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 prevalence of metabolic syndrome in the study participants was 7.8%. Our study revealed 5% of the patients overweight, and 1.4% obese. In this study, the mean triglyceride level was 118.5 mg/dL, and the mean high-density lipoprotein (HDL) level was 36.2 mg/dL (men) and 36.7 mg/dL (women). This study found that the mean fasting blood glucose level was 88.6 gm/dL. Similarly, 3.5% of patients had increased systolic blood pressure, and 7.8% had raised diastolic blood pressure. Study shows that changes in triglyceride level (&lt;i&gt;p&lt;/i&gt; = 0.013), waist circumference, and HDL level (&lt;i&gt;p&lt;/i&gt; = 0.0001 and 0.0048, respectively) are significantly associated with smoking or alcohol consumption; however, change in blood pressure (&lt;i&gt;p&lt;/i&gt; = 0.013) and fasting blood sugar level (&lt;i&gt;p&lt;/i&gt; = 0.086) are not associated with smoking or alcohol consumption.&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;Study concluded that though a lower proportion of SCD patients met the criteria for metabolic syndrome than in studies conducted in developed countries, it is crucial to consider metabolic syndrome while managing patients with SCD. Nevertheless, the authors advocate a more comprehensive study to draw significant conclusions.&lt;/p&gt;\u0000 &lt;","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"913-919"},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.989","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438901","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":"A phase 1b/2 study evaluating efficacy and safety of MP0250, a designed ankyrin repeat protein (DARPin) simultaneously targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib and dexamethasone, in patients with relapsed or refractory multiple myeloma","authors":"Stefan Knop,&nbsp;Monika Szarejko,&nbsp;Norbert Grząśko,&nbsp;Sara Bringhen,&nbsp;Karolin Trautmann-Grill,&nbsp;Artur Jurczyszyn,&nbsp;Angelo Vacca,&nbsp;Cyrus Khandanpour,&nbsp;Barbara Gamberi,&nbsp;Ludek Pour,&nbsp;Katrine F. Iversen,&nbsp;Michael T. Stumpp,&nbsp;Cosima Suter,&nbsp;Keith M. Dawson,&nbsp;Christof Zitt,&nbsp;Philippe Legenne,&nbsp;Vaia Stavropoulou,&nbsp;Martin F. Fey,&nbsp;Nicolas Leupin,&nbsp;Hartmut Goldschmidt","doi":"10.1002/jha2.968","DOIUrl":"https://doi.org/10.1002/jha2.968","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>MP0250 is a designed ankyrin repeat protein that specifically inhibits both vascular endothelial growth factor A (VEGF-A) and hepatocyte growth factor (HGF), aiming at potentiating cancer therapy by disrupting the tumour microenvironment. Encouraging results from a phase 1 trial of MP0250 in patients with solid tumours prompted further investigation in multiple myeloma (MM) as both MP0250 targets are reported to be drivers of MM pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>In this open-label, single-arm phase 1b/2 study (NCT03136653) in patients with proteasome inhibitor- and/or immunomodulatory drug-relapsed or refractory MM, MP0250 was administered every 3 weeks with standard bortezomib/dexamethasone regimen.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>Thirty-three patients received at least one dose of MP0250. The most frequent treatment-related adverse events were arterial hypertension (58.1%), thrombocytopenia (32.3%), proteinuria (29.0%) and peripheral oedema (19.4%). Of the 28 patients evaluable for response (median age: 60 [range 44–75]), nine achieved at least partial response, corresponding to an overall response rate of 32.1% (95% confidence interval [CI]: 17.9%, 50.7%), with a median duration of response of 8 months (95% CI 5–NR). An additional three patients achieved minimal response and nine stable diseases as the best overall response. Overall median progression-free survival was 4.2 months (95% CI 1.9–7.1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>These findings are in line with the results of recent trials testing new agents on comparable patient cohorts and provide initial evidence of clinical benefit for patients with refractory/relapsed MM treated with MP0250 in combination with bortezomib/dexamethasone. Further clinical evaluation in the emerging MM treatment landscape would be required to confirm the clinical potential of MP0250.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"940-950"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.968","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438890","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":"Novel method for assessing sinusoidal obstruction syndrome using four-dimensional computed tomography","authors":"Saori Shimoyama-Ibuki,&nbsp;Satoshi Iyama,&nbsp;Yoshiya Ohashi,&nbsp;Kento Ono,&nbsp;Yusuke Sugama,&nbsp;Chisa Fujita,&nbsp;Akari Goto,&nbsp;Hiroto Horiguchi,&nbsp;Akihito Fujimi,&nbsp;Takeo Tanaka,&nbsp;Kohichi Takada,&nbsp;Koh-Ichi Sakata,&nbsp;Masayoshi Kobune","doi":"10.1002/jha2.990","DOIUrl":"https://doi.org/10.1002/jha2.990","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>To diagnose sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), transabdominal ultrasonography is usually used to detect hemodynamic changes, but we tried to detect the changes using four-dimensional computed tomography (4D-CT). A 42-year-old Japanese woman was diagnosed with late-onset SOS/VOD with transabdominal ultrasonography and was also assessed using 4D-CT. Method We analyzed the portal vein (PV) contrast effect every 1.5 seconds and plotted the values of the contrast effect. With this graph, we analyzed three hemodynamic parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>We found that these parameters correlated with the patient's status and indicated stasis due to sinusoid constriction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>4D-CT may become a helpful tool to diagnose and follow up with SOS/VOD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1038-1042"},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.990","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439126","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":"Unveiling the nephrotoxic profile of BCR-ABL tyrosine kinase inhibitors: A real-world experience in Africa","authors":"Zekarias Seifu Ayalew,&nbsp;Gebeyehu Tessema Azibte,&nbsp;Fisihatsion Tadesse,&nbsp;Biruk Abate Legesse,&nbsp;Zerubabel Getahun Kiflu,&nbsp;Mahlet Tsige Weldeamanuel,&nbsp;Kibrekidusan Aynekulu Tsige,&nbsp;Bereket Abraha Molla,&nbsp;Addisu Melkie Ejigu","doi":"10.1002/jha2.988","DOIUrl":"https://doi.org/10.1002/jha2.988","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The efficacy of BCR-ABL tyrosine kinase inhibitors (TKIs) in treating chronic myelogenous leukemia and other malignancies is well-documented. However, concerns about potential nephrotoxicity have raised questions. This study, conducted at Tikur Anbesa Specialized Hospital (TASH) in Addis Ababa, Ethiopia, aimed to investigate the association between TKIs and renal toxicities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A hospital-based cross-sectional design was used to enroll 260 TASH patients actively receiving BCR-ABL TKIs. Demographic information, diagnoses, treatment details, and laboratory test results were collected for each participant's Electronic Medical Record. The primary goal was to assess adverse renal events, a combination of events of a decrease in estimated glomerular filtration rate (eGFR) exceeding 30% from baseline, significant proteinuria, and a diagnosis of acute kidney injury (AKI) or chronic kidney disease (CKD). A logistic regression model was used to analyze the data and identify factors associated with developing adverse renal events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our analysis revealed a statistically significant decrease in eGFR following treatment with TKIs. However, the observed rate of adverse renal events (13.1%) was lower than reported in some previous studies. Factors significantly associated with adverse renal events included longer TKI duration, male sex (protective), hypertension, HIV infection, and achieving complete molecular remission and/or a complete hematologic response. No significant associations were found with diabetes mellitus, age, angiotensin-converting enzyme inhibitors use, or baseline creatinine level.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>While this study found that BCR-ABL TKIs can lead to a decline in eGFR, AKI, and CKD, it also demonstrated that they were relatively safer in our study population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 4","pages":"749-756"},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.988","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994060","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":"Antiphospholipid syndrome, monoclonal gammopathy, and cryoglobulinemia overlap leading to recurrent cutaneous microvascular thrombosis: A case report and retrospective cohort study","authors":"Alexandra Bohm,&nbsp;Bo Angela Wan,&nbsp;Amir Karin,&nbsp;Lauren J. Lee,&nbsp;Agnes Y. Y. Lee,&nbsp;Edward M. Conway,&nbsp;Chieh Min Benjamin Lai","doi":"10.1002/jha2.987","DOIUrl":"10.1002/jha2.987","url":null,"abstract":"<p>Antiphospholipid syndrome (APS), cryoglobulinemia, and monoclonal gammopathies are variably accompanied by thrombotic complications. We describe a patient with recurrent skin microvascular thrombosis, APS, cryoglobulinemia, marginal zone lymphoma, and IgMκ monoclonal gammopathy, responsive to chemoimmunotherapy. The cryoglobulin fraction contained the IgMκ paraprotein, while antiphospholipid antibodies (aPL) were predominantly in the cryosupernatant. A retrospective analysis of aPL-positive patients in our institution showed that 8.1% co-expressed monoclonal gammopathy. These overlap patients had thrombotic complications and most had recurrences. Patients with multiple gammopathies of thrombotic significance may have several autoantibodies and constitute a high-risk group.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"971-975"},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.987","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797176","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":"IDH2 mutation accelerates TPO-induced myelofibrosis with enhanced S100a8/a9 and NFκB signaling in vivo","authors":"Chien-Chin Lin,&nbsp;Chi-Yuan Yao,&nbsp;Yu-Hung Wang,&nbsp;Yueh-Chwen Hsu,&nbsp;Chang-Tsu Yuan,&nbsp;Tsung-Chih Chen,&nbsp;Chia-Lang Hsu,&nbsp;Sze-Hwei Lee,&nbsp;Jhih-Yi Lee,&nbsp;Pin-Tsen Shih,&nbsp;Chein-Jun Kao,&nbsp;Po-Han Chuang,&nbsp;Yuan-Yeh Kuo,&nbsp;Hsin-An Hou,&nbsp;Wen-Chien Chou,&nbsp;Hwei-Fang Tien","doi":"10.1002/jha2.983","DOIUrl":"10.1002/jha2.983","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p><i>IDH2</i> mutation is an unfavorable prognostic factor in patients with primary myelofibrosis (PMF) but its effect on myelofibrosis (MF) remains largely unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we aimed to elucidate the roles of <i>IDH2</i> mutation in the development and progression of MF by transcriptomic and molecular techniques using the <i>Idh2</i>^R172K transgenic mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that thrombopoietin (TPO)-overexpressed <i>Idh2</i>^R172K (<i>Idh2</i>^R172K + TPO) mice had accelerated progression to MF, compared with TPO-overexpressed <i>Idh2-</i>wild (WT + TPO) mice, showing activation of multiple inflammatory pathways, among which nuclear factor κB (NFκB) was the most significantly enhanced. Single-cell transcriptomes of the marrow cells in early MF showed that <i>S100a8/a9</i> expression was mainly confined to neutrophil progenitors in the WT + TPO mice, but highly expressed in several types of myeloid precursor cells, including the megakaryocyte progenitors in the <i>Idh2</i>^R172K + TPO group. Furthermore, <i>Idh2</i>^R172K mice at age of 18 months had larger spleens, increased <i>S100a8/a9-Tlr4</i> expression, and elevated serum S100a8/a9 levels compared with WT mice. PMF patients with <i>IDH2</i> mutations had higher bone marrow plasma S100A8/A9 levels than those without <i>IDH2</i> mutations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, our findings showed that <i>IDH2</i> mutation induced proinflammatory effects, which further exacerbated MF, as evidenced by the increase in S100a8/a9 levels and NFκB hyperactivation in <i>Idh2</i>^R172K + TPO mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 4","pages":"738-748"},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.983","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797076","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":"Bleeding management in type 3 von Willebrand disease with anti-von Willebrand factor inhibitor: A literature review and case report","authors":"Aurélie Briane,&nbsp;Valérie Horvais,&nbsp;Marianne Sigaud,&nbsp;Marc Trossaërt,&nbsp;Nicolas Drillaud,&nbsp;Catherine Ternisien,&nbsp;Marc Fouassier,&nbsp;Antoine Babuty","doi":"10.1002/jha2.984","DOIUrl":"10.1002/jha2.984","url":null,"abstract":"<p>Treatment of type 3 von Willebrand disease by infusion of von Willebrand factor (VWF) and factor VIII (FVIII) concentrates may lead to the development of anti-VWF antibodies, challenging haemostasis management. The systematic review of the literature presented here retrieved 15 such cases (surgery <i>n</i> = 11, bleeding <i>n</i> = 4). The heterogeneous patient management mostly involved continuous infusion of FVIII, or recombinant FVIIa together with various other strategies. Off-label infusion of the bispecific monoclonal antibody emicizumab was prescribed in three cases and in a complex local case, ultimately well-controlled with emicizumab. This illustrates the fact that emicizumab appears as a therapeutic option in this context of allo-immunisation.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"964-970"},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.984","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141802875","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}