EJHaem最新文献

{"title":"Next Generation Sequencing Allows Identification of a Novel Mutation in the TfR2 Gene and Outperforms the Conventional Diagnostic Techniques","authors":"Miriam Longo,&nbsp;Erika Paolini,&nbsp;Marica Meroni,&nbsp;Felice Cinque,&nbsp;Cristina Bertelli,&nbsp;Giuseppina Pisano,&nbsp;Marco Maggioni,&nbsp;Anna Ludovica Fracanzani,&nbsp;Rosa Lombardi,&nbsp;Paola Dongiovanni","doi":"10.1002/jha2.70073","DOIUrl":"https://doi.org/10.1002/jha2.70073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Type 3 hereditary hemochromatosis (HH) is a rare genetic disease due to mutations in the transferrin receptor 2 (<i>TFR2</i>) gene.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Here, we describe the case of an Italian patient presenting with hyperferritinemia and hepatic iron accumulation, not evidenced by magnetic resonance imaging, that was subsequently classified as HH Type 3 by the identification of the novel frameshift mutation c.523_524delC&gt;T (p. Leu175Aspfs*41) in exon 4 of <i>TFR2</i> gene through the whole exome sequencing (WES) approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>WES would allow to diagnose rare HH-related diseases in patients with unexplained hepatic iron overload and/or aberrant circulating iron parameters.</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 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482284","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":"Characteristics, Treatment Patterns, and Outcomes of Patients with Multiple Myeloma, Including Those Who are Triple-Class Exposed: A Retrospective Cohort Study in England Using National Cancer Registry Data","authors":"Carmen Tsang,&nbsp;Kellyn Arnold,&nbsp;Charles Duffield,&nbsp;Stavros Oikonomou,&nbsp;Thomas Price,&nbsp;Tarana Mehdikhanova,&nbsp;Samuel Wood,&nbsp;Mamta Garg","doi":"10.1002/jha2.70064","DOIUrl":"https://doi.org/10.1002/jha2.70064","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Multiple myeloma (MM) prognosis worsens once patients become triple-class exposed (TCE) to at least one treatment in each class: immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective study using the Cancer Analysis System database to assess characteristics, treatment patterns, and clinical outcomes for adults diagnosed with MM between 2014 and 2020. The main cohort included patients ≥18 years-old diagnosed with incident MM (including TCE patients) who had at least one record of systemic anticancer therapy treatment within 30 days prior to, on, or any time after their diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The main cohort comprised 14,990 patients, predominantly white and male, with a median age at diagnosis of 71 years. Of these, 848 (5.6%) became TCE. In the main cohort (<i>n</i> = 14,990), 57.2% of patients received only one line of therapy, and &gt;50% of all first-line regimens included bortezomib. Median overall survival (OS) from diagnosis was 51.5 months. After becoming TCE (<i>n</i> = 848), median OS was 13.2 months and median time to next treatment or death was 5.7 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provides current evidence on real-world OS and management for patients with MM in England, including those who become TCE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482380","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":"Plasma Cell Crystalline Inclusions in ALK-Negative Anaplastic Large Cell Lymphoma","authors":"Hiromi Kinoshita,&nbsp;Tsugumi Satoh,&nbsp;Hidekazu Kayano,&nbsp;Naoki Takahashi,&nbsp;Yasuhiro Ebihara","doi":"10.1002/jha2.70080","DOIUrl":"https://doi.org/10.1002/jha2.70080","url":null,"abstract":"&lt;p&gt;A 79-year-old woman presented with hematochezia. Endoscopic examination revealed a polyp in the rectum, and endoscopic mucosal resection was performed. The pathological diagnosis was carcinoma in adenoma, pTis (M). No further treatment was performed for this tumor. At that time, worsened hepatic dysfunction and fever were noted. A computed tomography scan showed systemic lymph nodes swelling and hepatosplenomegaly, indicating malignant lymphoma. Laboratory data showed markedly elevated soluble interleukin-2 receptor and lactate dehydrogenase levels of 48,897 U/mL (reference value: 204–587) and 3699 U/L (reference value: 124–222), respectively, which supported the diagnosis of lymphoma. Immunoglobulin levels were not elevated.&lt;/p&gt;&lt;p&gt;Bone marrow showed aggregations of abnormal lymphoid cells (Figure 1a), which possessed distinct nucleoli, abundant cytoplasm, and moderate to large irregularly shaped nuclei (Figure 1b). These cells were positive for CD30 (Figure 1c) and CD4 (Figure 1d), and negative for PAX-5, CD20, CD2, CD3, CD5, and CD7. Anaplastic lymphoma kinase (ALK) and Epstein–Barr virus-encoded small RNA in situ hybridization were negative. Light chain restriction was not detected by flow cytometry. Finally, a diagnosis of ALK-negative anaplastic large cell lymphoma (ALCL; clinical Stage 4) was made.&lt;/p&gt;&lt;p&gt;In addition to ALCL cell infiltration in bone marrow, plasma cells with crystalline inclusions, which exhibited a relatively larger, rectangular or rhomboid morphology, were found (Figure 2a–c; arrows), although the number of plasma cells were not increased (2.2%). These cells were positive for CD138 (Figure 2d), and these crystalline inclusions were negative for kappa and lambda immunoglobulins.&lt;/p&gt;&lt;p&gt;ALCL is a malignancy of mature T lymphocytes with expression of CD30. In a previous review of synchronous solid tumor and lymphoma, most cases involved the combination of adenocarcinoma and B-cell lymphoid lymphoma. ALCL occurring simultaneously with solid tumor is extremely rare, but there is one reported case of ductal breast carcinoma and breast-implant-associated ALCL. The relationship between rectal carcinoma in adenoma and the onset of ALCL in the present case is unknown. ALCL cells and plasma cells with inclusions were not detected in the polyp samples from the rectum of this patient.&lt;/p&gt;&lt;p&gt;Intracytoplasmic inclusions are occasionally seen in plasmacytoid or B-cell lymphoproliferative disorders such as multiple myeloma, but are rarely found in other diseases.&lt;/p&gt;&lt;p&gt;Some reports have described the detection of plasma cells around ALCL cells, but plasma cells with inclusions were not noted. The mechanism by which intracytoplasmic crystalline inclusions are produced is not well understood, but is related to the abnormal accumulation of cytoplasmic immunoglobulins secondary to disruption of the protein synthesis pathway.&lt;/p&gt;&lt;p&gt;In the present case, the patient's general condition was poor, so aggressive treatment for ALCL was not possibl","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492653","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":"Venetoclax Consolidation After Bruton Tyrosine Kinase Inhibitor Treatment for Patients With Chronic Lymphocytic Leukemia","authors":"Benjamin Heyman,&nbsp;Michael Choi,&nbsp;Thomas J. Kipps","doi":"10.1002/jha2.70085","DOIUrl":"https://doi.org/10.1002/jha2.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Bruton tyrosine kinase inhibitors (BTKi) are highly effective therapy for chronic lymphocytic leukemia (CLL) but can lead to long-term side effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a retrospective analysis of venetoclax consolidation of 20 patients with CLL after initial BTKi discontinuation. Patients were administered either single-agent venetoclax or in combination with obinutuzumab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The best peripheral blood minimal residual disease (MRD) response was undetectable MRD, occurring in 89% of patients. With a median follow-up of 47.4 months, both the median progression-free survival and time-to-next treatment were not reached.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Venetoclax consolidation after BTKi is a feasible treatment strategy for patients with CLL, with encouraging efficacy deserving further study.</p>\u0000 \u0000 <p><b>Clinical Trial Registration</b>: N/A</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473242","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 Bone Marrow Classic Hodgkin Lymphoma With Haemophagocytic Lymphohistiocytosis","authors":"Chun-Tsu Lee","doi":"10.1002/jha2.70014","DOIUrl":"https://doi.org/10.1002/jha2.70014","url":null,"abstract":"&lt;p&gt;A previously well, 25-year-old man was referred by his GP for persistent fever, anorexia, night sweats and weight loss for the past 1 month. He was febrile and lethargic, with no palpable hepatosplenomegaly or lymphadenopathy. An initial CT scan showed no suspicious masses or organomegaly. Full blood count showed pancytopenia with a haemoglobin of 8.8 g/dL, platelet count of 50 × 10&lt;sup&gt;9&lt;/sup&gt;/L and leucocyte count of 1.5 × 10&lt;sup&gt;9&lt;/sup&gt;/L (neutrophil 0.8 × 10&lt;sup&gt;9&lt;/sup&gt;/L). Liver function tests were deranged with raised bilirubin and transaminases. Marked hyperferritinemia of 20,000 ug/L and high LDH of 1080 IU/mL were observed together with prolonged PT and APTT with hypofibrinogenemia of 1.1 g/L and hypertriglyceridemia of 6.8 mmol/L. Autoimmune workup, plasma HIV and EBV viral load were negative. Bone marrow (BM) aspirate was performed, showing the presence of Reed–Sternberg cells and Hodgkin cells, characteristics of classical Hodgkin Lymphoma (HL). There were increased histiocytic activities with brisk hemophagocytic activities of note (Figure 1). Histology showed lymphomatous infiltration featuring scattered atypical medium-sized to large cells with round to lobated nuclei and occasional prominent nucleoli, accompanied by small lymphocytes, occasional plasma cells, eosinophils and neutrophils (Figure 1). Immunohistochemistry showed scattered large CD30+ neoplastic cells that co-express PAX5 but not CD20, CD2 nor CD3, accompanied by numerous CD2+ CD3+ reactive T-cells. In situ hybridization for EBER was negative. T-cell receptor gene rearrangements showed polyclonal expansion of T-cells. PET scan showed diffuse intense, FDG-avid uptake was seen along the axial and proximal appendicular skeleton (SUVmax 14.1). Diffuse FDG-avid uptake was seen involving the liver and spleen (SUVmax 5.1 vs. liver SUVmax 4.1), but they were not enlarged. No other suspicious FDG-avid lesions or adenopathy were detected. Overall findings were compatible with primary BM HL with Haemophagocytic Lymphohistiocytosis (HLH). His condition deteriorated with worsening cytopenias and liver functions. Dexamethasone, Etoposide and IVIG were swiftly commenced to control cytokine storm and reactive T-cell proliferation. With other supportive measures including blood products, antimicrobials and myeloid growth factors, his condition improved and he was started on definitive chemotherapy consisting of Brentuximab vedotin plus Doxorubicin, Vinblastine and Dacarbazine. He achieved a complete metabolic response after six cycles of chemotherapy.&lt;/p&gt;&lt;p&gt;In the era of PET scanning, BM biopsies are rarely conducted for HL. Nevertheless, it is unusual to detect Reed–Sternberg and Hodgkin cells in an aspirate because the lymphomatous infiltration induces marrow fibrosis, hampering the aspiration process. BM involvement by HL is observed in 5%–15% of patients and is usually associated with lymphadenopathy [&lt;span&gt;1, 2&lt;/span&gt;]. Primary BM HL is rare (0.25%) and usually occurs in HIV-p","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323440","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":"Manifestations of Teclistamab-Associated Uveitis","authors":"Gabriel Castilho Barbosa,&nbsp;Shahzad Raza,&nbsp;Aneel Chowdhary,&nbsp;Sumit Sharma","doi":"10.1002/jha2.70083","DOIUrl":"https://doi.org/10.1002/jha2.70083","url":null,"abstract":"&lt;p&gt;Teclistamab (Janssen, Beerse, Belgium), a novel bispecific antibody for relapsed or refractory multiple myeloma (RRMM) works by binding B-cell maturation antigen (BCMA) and CD3 on T cells, activating the T cells to destroy the myeloma cells expressing BCMA [&lt;span&gt;1&lt;/span&gt;]. Teclistamab has shown remarkable efficacy in RRMM. It is approved by the FDA for adult patients who have received at least four lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD 38 monoclonal antibody [&lt;span&gt;1&lt;/span&gt;]. Teclistamab is associated with adverse events, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and an increased risk of infections [&lt;span&gt;1&lt;/span&gt;]. Recently, Liu et al. [&lt;span&gt;2&lt;/span&gt;] reported a single case of unilateral sclerouveitis with hypopyon occurring within days of initiating teclistamab.&lt;/p&gt;&lt;p&gt;Here, we present two cases of acute anterior uveitis associated with teclistamab therapy occurring at different time points after treatment initiation. Both cases were successfully managed with topical corticosteroids, and infectious or autoimmune etiologies were ruled out. These cases highlight the need for vigilance in recognizing potential ocular toxicities of novel therapies, emphasizing the relevance of early detection and management.&lt;/p&gt;&lt;p&gt;In this manuscript, we present two distinct presentations of uveitis associated with teclistamab therapy. As a novel medication for RRMM, teclistamab has rapidly gained clinical relevance. To date, only one published report has described a case of teclistamab-associated uveitis, suggesting that such events may be underrecognized [&lt;span&gt;2&lt;/span&gt;]. Notably, no ocular adverse events were reported in the clinical trials evaluating teclistamab, including the pivotal MajesTEC-1 study, highlighting the rarity of these findings [&lt;span&gt;1&lt;/span&gt;]. As teclistamab use becomes more widespread, identifying and documenting these rare adverse events is essential to guide timely diagnosis and management.&lt;/p&gt;&lt;p&gt;Case 1 shares similarities with the previously reported case by Liu et al. [&lt;span&gt;2&lt;/span&gt;], with both patients developing acute anterior uveitis shortly after starting teclistamab, suggesting a potential pattern of early inflammatory reaction to the drug. However, unlike Liu et al.’s case, which involved unilateral uveitis with hypopyon, our case presented bilaterally, with differing severity between the eyes. The right eye exhibited more pronounced symptoms, including a fibrin plaque in the anterior chamber, while no hypopyon was observed. The patient responded robustly to topical corticosteroids, with complete resolution of uveitis and the fibrin plaque within two weeks.&lt;/p&gt;&lt;p&gt;Conversely, Case 2 presented with delayed uveitis, developing seven months after teclistamab initiation. The patient exhibited anterior and intermediate uveitis with persistent vitreous involvement. This delay may indicate cumulative immune dysregulation, contribut","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315298","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 Flavonoid Derivatives Show Potent Efficacy in Human Lymphoma Models","authors":"Eugenio Gaudio,&nbsp;Paulina Biniecka,&nbsp;Alberto J. Arribas,&nbsp;Eleonora Cannas,&nbsp;Guido J. R. Zaman,&nbsp;Derya Unutmaz,&nbsp;Francesco Bertoni,&nbsp;Dan F. Stoicescu","doi":"10.1002/jha2.70081","DOIUrl":"https://doi.org/10.1002/jha2.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite significant therapeutic progress, many lymphoma subtypes remain difficult to manage due to resistance, relapse, and dose-limiting toxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To elucidate the mechanism of action of the semi-synthetic flavonoid derivative (SND) compounds, we conducted a screening of cancer cell lines using proliferation, cell cycle, and apoptosis assays. We then performed computational modeling of the compounds’ binding to tubulin, and finally evaluated in vivo activity using nanoNail technology alongside xenograft experiment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we describe a series of SNDs that exhibit low-nanomolar to picomolar cytotoxicity across multiple lymphoma models, including those resistant to BTK and PI3K inhibitors. Mechanistic studies show that these compounds trigger robust apoptosis via cytoskeletal disruption and mitochondrial dysfunction. Notably, SND207 also potently inhibits Protein Kinase N1, suggesting a synergistic link between kinase blockade and cytoskeletal interference. High-throughput profiling places them near classical microtubule agents, although tubulin assays indicate more nuanced mechanisms than straightforward stabilization or depolymerization. In murine xenografts, SND207 significantly reduced tumor burden, and its combination with a BTK inhibitor demonstrates potential synergy. Furthermore, localized NanoNail delivery achieves high intratumoral drug concentrations at low doses, underscoring a favorable therapeutic index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, these findings highlight the translational promise of the SND series for future studies in the lymphoma field.</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":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315297","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":"Time Without Transfusion Reliance (TWiTR): Integrating Survival Quality Into Myelofibrosis Treatment Strategies Based on the Phase 3 SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM Trials","authors":"Ruben A. Mesa,&nbsp;Moshe Talpaz,&nbsp;Flora Mazerolle,&nbsp;Boris Gorsh,&nbsp;Manal M'Hari,&nbsp;Antoine Regnault,&nbsp;Catherine Ellis,&nbsp;Zhaohui Wang,&nbsp;Molly Purser,&nbsp;Tom Liu,&nbsp;Bryan Strouse,&nbsp;Dwaipayan Patnaik","doi":"10.1002/jha2.70075","DOIUrl":"https://doi.org/10.1002/jha2.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Myelofibrosis is characterized by debilitating constitutional symptoms and anemia, which negatively impact survival and quality of life. Red blood cell transfusions form the basis of anemia management in myelofibrosis but dependence on transfusions is further associated with poorer survival and quality of life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Time without transfusion reliance (TWiTR), a method integrating transfusion dependence and survival quality, was applied to three Phase 3 trials of momelotinib in myelofibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TWiTR demonstrated that patients treated with momelotinib versus comparators spent more time free from transfusions and anemia events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Momelotinib may lead to improved survival quality for patients with myelofibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifiers: NCT01969838, NCT02101268, and NCT04173494</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309018","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":"Severe Thrombocytopenia Is Associated with a Genetic Variant in the Helicase Domain of SLFN14 Gene: A Case Report","authors":"Kun Yang,&nbsp;Peixiao Fu,&nbsp;Jinyun Xu,&nbsp;Hao Jiang,&nbsp;Jie Yu,&nbsp;Chunhai Luo,&nbsp;Jiaowei Gu","doi":"10.1002/jha2.70068","DOIUrl":"https://doi.org/10.1002/jha2.70068","url":null,"abstract":"<p>Inherited thrombocytopenias (ITs) are a diverse group of hematological disorders. This study reports a novel case of severe thrombocytopenia in two male twins from nonconsanguineous parents. Whole exome sequencing (WES) identified a heterozygous genetic variant (c.1766T &gt; C; p.L589S) in the helicase domain of the <i>SLFN14</i> gene in the twins, their mother, and maternal grandmother, while the father and maternal grandfather did not carry the genetic variant. Despite carrying the genetic variant, the mother and maternal grandmother showed no abnormal phenotypes. The twins exhibited significantly reduced platelet counts, abnormal megakaryocyte accumulation, and arrested maturation, broadening the spectrum of SLFN14-related thrombocytopenia.</p><p><b>Clinical Trial Registration</b>: The authors confirm that registration of a clinical trial is not necessary for this submission.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273318","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":"Risk adapted therapy for newly diagnosed multiple myeloma delivered through local cytogenetic laboratories in a National Clinical Trial: UKMRA RADAR study","authors":"Dipal Mehta,&nbsp;Robert Cicero,&nbsp;Laura Chiecchio,&nbsp;Samir Asher,&nbsp;Martin Kaiser,&nbsp;Sarah Gooding,&nbsp;Kara-Louise Royle,&nbsp;Catherine Olivier,&nbsp;Doina Levinte,&nbsp;Charlotte Kennaway,&nbsp;Karthik Ramasamy,&nbsp;Kwee Yong,&nbsp;Matthew Jenner","doi":"10.1002/jha2.1015","DOIUrl":"https://doi.org/10.1002/jha2.1015","url":null,"abstract":"<p>The UKMRA RADAR study is a phase II/III clinical trial for newly diagnosed multiple myeloma patients eligible for autologous stem cell transplant. It offers a risk-adapted approach with the addition of isatuximab for genetically high-risk patients, evaluated using local cytogenetics laboratories rather than centralised testing. We have observed excellent overall success rates, with &gt; 90% patients assigned to a risk-adapted pathway following cytogenetic testing in 25 local laboratories nationwide, with clinically-relevant turnaround times allowing &gt; 70% patients to commence isatuximab at the earliest opportunity if indicated. This paves the way for providing standard-of-care risk-adapted treatment for multiple myeloma patients in the UK.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308740","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}