HemaSphere最新文献

{"title":"Emergency hematopoiesis in sepsis: A pathway to myeloid clonal expansion.","authors":"Olisaemeka Ogbue, Tariq Kewan, Serhan Unlu, Kartik Lakhotiya, Omar Mehkri, Rayna Ellison, Francois Fadell, Felipe de Almeida Sartori, Asfand Yar Cheema, Mark Orland, Arda Durmaz, Zachary Brady, Jennifer VanOudenhove, Abhay Singh, Valeria Visconte, Lourdes Mendez, David S Bosler, Stephanie Halene, Mohammed J Al-Jaghbeer, Abhijit Duggal, Jaroslaw P Maciejewski, Carmelo Gurnari","doi":"10.1002/hem3.70495","DOIUrl":"https://doi.org/10.1002/hem3.70495","url":null,"abstract":"","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 11","pages":"e70495"},"PeriodicalIF":11.3,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149297110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Zhou and Shan: Interpreting long-term response to rituximab in immune thrombocytopenia","authors":"Galina Tsykunova, Eskild Bendix Kristiansen, Tor Henrik Anderson Tvedt, Henrik Frederiksen, Christian Fynbo Christiansen, Marie Linder, Shahram Bahmanyar, Waleed Ghanima","doi":"10.1002/hem3.70520","DOIUrl":"https://doi.org/10.1002/hem3.70520","url":null,"abstract":"<p>We thank Zhou and Shan for their careful reading of our study and for highlighting important questions about the interpretation of registry data on rituximab in immune thrombocytopenia (ITP).<span><sup>1</sup></span> We welcome the opportunity to clarify these issues.</p><p>First, Zhou and Shan note that inclusion of patients treated early with rituximab depended on subsequent documentation of ITP, potentially underrepresenting patients with durable early responses. As stated in our Methods section, patients were required to have at least two inpatient or outpatient diagnoses of ITP separated by more than 6 months. The criterion was met by a registered ITP diagnosis at an inpatient or outpatient specialist visit. Confirmation of thrombocytopenia was part of diagnostic validation by medical record review, which required at least one documented platelet count below 150 × 10<sup>9</sup>/L.<span><sup>2</sup></span> In the Nordic countries, patients treated with rituximab are routinely followed in specialist care for at least 12 months after treatment, and these visits are registered with an ITP diagnosis irrespective of whether the platelet count has recovered. This practice mitigates the concern that inclusion preferentially captures patients with persistent disease.</p><p>Nevertheless, we acknowledge that a patient whose entire disease course was completed within 6 months of the first contact could not have been captured. Such exclusion would, if present, lead to underestimation rather than overestimation of response duration. We cannot determine whether or to what extent this affected our estimated median response duration of 5.4 years.</p><p>Second, Zhou and Shan rightly point out that concomitant corticosteroid use may have contributed to the longer response duration observed in the previously untreated group. A meaningful comparison by regimen is, however, difficult: only 32 of the 123 previously untreated patients received rituximab without concomitant corticosteroids, and information on corticosteroid dose was missing or incomplete for a substantial proportion of patients.</p><p>In a backward-elimination model, co-administration of corticosteroids was associated with sustained response at 5 years (risk ratio, 8.29; 95% confidence interval, 2.35–29.16) in the non-pretreated group. The wide confidence interval indicates substantial uncertainty and should not be interpreted as clear evidence of a causal effect. Further stratification would yield small subgroups and imprecise estimates, limiting our ability to distinguish the contributions of treatment timing and co-administration of corticosteroids, which the 8-week washout before response assessment does not fully disentangle either.</p><p>Third, we agree that the end of the study period in 2018 limited the opportunity for some patients to reach the predefined 2- and 5-year sustained response endpoints (SR2 and SR5). Among the 503 patients who achieved an initial response, all reached the 6-","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149258207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpreting long-term response to rituximab in immune thrombocytopenia: Cohort construction, treatment attribution, and dynamic prognostication","authors":"Xin Zhou, Ningning Shan","doi":"10.1002/hem3.70519","DOIUrl":"https://doi.org/10.1002/hem3.70519","url":null,"abstract":"<p>We read with great interest the study by Tsykunova et al.<span><sup>1</sup></span> published in <i>HemaSphere</i>. Drawing on a large Nordic cohort, the authors comprehensively characterized initial and sustained long-term responses to rituximab in patients with immune thrombocytopenia (ITP), providing valuable real-world evidence. We wish to add several considerations regarding cohort construction, concomitant corticosteroid use, and long-term outcome assessment that may further inform the interpretation and clinical implications of these findings.</p><p>Of the 759 patients, 444 received rituximab before fulfilling the registry criteria for chronic ITP, although cohort eligibility required at least two ITP diagnoses more than 6 months apart. The upfront group, comprising 123 previously untreated patients, may therefore represent early-treated patients with subsequent disease documentation rather than all patients receiving rituximab early. Durable early responders may have fewer subsequent ITP encounters, whereas patients with persistent disease remain more likely to be documented and followed. Such selection related to subsequent disease trajectories may affect the representativeness of this group, although its direction and magnitude remain uncertain.<span><sup>2</sup></span></p><p>The authors appropriately acknowledge that concomitant corticosteroids may partly explain the longer response duration in the upfront group. Corticosteroid use differed markedly between the upfront and pretreated groups (74.0% vs. 15.6%), suggesting that the observed durability may reflect both treatment timing and combination therapy. Randomized trials have shown that rituximab plus dexamethasone improves sustained response and delays relapse compared with dexamethasone alone.<span><sup>3, 4</sup></span> Moreover, excluding platelet-elevating therapy only during the 8 weeks preceding response assessment may not fully separate the contributions of corticosteroids given at rituximab initiation. If available, outcomes stratified by concomitant corticosteroid use and regimen could further clarify the relationship between early rituximab use and durable response.</p><p>A further consideration concerns the assessment of long-term response. Because both rituximab treatment and registry follow-up ended in 2018, patients had unequal opportunities to complete 2- or 5-year follow-up. Although SR2 and SR5 were calculated among initial responders, the numbers with sufficient potential follow-up at each landmark remain unclear. These estimates may therefore reflect both response durability and observable follow-up time. Reporting landmark-eligible responders and numbers at risk, or providing time-to-event estimates, could help contextualize the 31.4% SR5 rate. The STROBE statement likewise emphasizes transparent reporting of follow-up duration, numbers analyzed, and loss to follow-up.<span><sup>5</sup></span></p><p>Complete response (CR) at 3–6 months was closely associated w","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149258206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of simultaneous [18F]FDG-PET/MRI in refractory multiple myeloma treated with anti-BCMA CAR T","authors":"Bastien Jamet,&nbsp;Huajun Sun,&nbsp;Chloé François,&nbsp;Hatem Necib,&nbsp;Aurélien Monnet,&nbsp;Éric Frampas,&nbsp;Nicolas Blin,&nbsp;Nicoletta Libera Lilli,&nbsp;Caroline Bodet-Milin,&nbsp;Philippe Moreau,&nbsp;Françoise Kraeber-Bodere,&nbsp;Cyrille Touzeau","doi":"10.1002/hem3.70515","DOIUrl":"https://doi.org/10.1002/hem3.70515","url":null,"abstract":"<p>The aims of this study were to assess the prognostic value for progression-free survival (PFS) and the diagnostic value (detection rate of multiple myeloma [MM]–related medullary and extra-medullary disease) of whole-body simultaneous [¹⁸F]fluorodeoxyglucose-positron emission tomography coupled with magnetic resonance imaging (WB[¹⁸F]FDG-PET/MRI) performed before and after idecabtagene-vicleucel (ide-cel) therapy in patients with triple-class (or more) relapsed/refractory multiple myeloma (RRMM). A total of 73 patients were prospectively enrolled in this monocentric cohort, and 72 of them underwent WB[¹⁸F]FDG-PET/MRI imaging before ide-cel (after personalized bridging therapy). Overall, active disease was detected in 64/72 patients (89%). Multivariate analyses showed that the presence of diffuse bone marrow involvement (BMI) pattern on PET (hazard ratio [HR]: 2.65; 95% CI: 1.16–6.1, P = 0.02) or MRI (HR: 2.69; 95% CI: 1.28–5.66, P = 0.009) was associated with shorter PFS. A total of 66 patients underwent [¹⁸F]FDG-PET/MRI for response to ide-cel therapy assessment. Diffusion-weighted MRI (DW-MRI) detected residual disease (response assessment category [RAC]2 or higher according to MY-RADS) in 9/66 patients (14%) and PET (no complete metabolic response according to Deauville score) in 7/66 patients (11%). Overall, [¹⁸F]FDG-PET/MRI increased residual disease detection to 13 of 66 patients (20%). Patients with residual disease on DW-MRI (RAC2 or higher) had shorter PFS (HR: 4.11; 95% CI: 1.8–9.4; P &lt; 10⁻³) than those without (RAC1). Achieving at least a partial metabolic response on PET significantly improved the PFS (P = 0.0046) as well. The combination of [¹⁸F]FDG-PET and DW-MRI enabled the identification of three distinct risk groups, including a very high-risk group defined by both MRI and PET positivity.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149258740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mentorship in hematology: A multigenerational perspective on its role in shaping the future of the field","authors":"Rayan Bou-Fakhredin,&nbsp;Maria Domenica Cappellini,&nbsp;Ali Taher","doi":"10.1002/hem3.70517","DOIUrl":"10.1002/hem3.70517","url":null,"abstract":"&lt;p&gt;Mentorship is often described as the transfer of knowledge from one generation to the next. Our experience suggests that it is much more than that. As three individuals connected across three generations by a shared passion for advancing the care of patients with thalassemia, we have found mentorship to be a relationship built on trust, honesty, and shared purpose. It has shaped not only our scientific careers but also how we contribute to improving patient care, collaborate with colleagues, and think about our responsibilities in the scientific community as physicians and researchers. In this perspective, we reflect on our own mentorship journey in thalassemia and why we believe these relationships have been as important to advancing the field as scientific discovery itself.&lt;/p&gt;&lt;p&gt;Maria Domenica Cappellini, mentored by the late Professor Gemino Fiorelli and the late Professor Sir David Weatherall, represents the generation that laid the scientific foundations of modern thalassemia care. Ali Taher, mentored by Professor Victor Hoffbrand and Professor Cappellini, advanced that work by further characterizing different aspects of the disease, bridging research between the Middle East and global networks, and establishing regional scientific societies to foster local expertise and international collaboration. Rayan Bou-Fakhredin, the third generation of this mentorship lineage, began his clinical research journey in thalassemia with Ali Taher in Lebanon, who then introduced him to Maria Domenica Cappellini. He subsequently moved to Milan to pursue his PhD within Maria Domenica Cappellini's group, continuing his work in clinical and translational science in thalassemia. With the support and encouragement of both his mentors, who helped open doors to new opportunities and international collaborations, he was able to undertake part of his PhD training in the United States, gaining exposure to different research environments and broadening his scientific perspective. After completing his PhD, Rayan chose to take his experience beyond academia and pursue a career in industry, bringing his scientific expertise in hemoglobinopathies into a broader strategic context.&lt;/p&gt;&lt;p&gt;Looking back, what connects our three careers is not that we followed the same path, but that each mentor encouraged the next generation to find their own. Each one of us ultimately grew in a different direction while remaining connected by the same values and commitment to improving care for patients with thalassemia. For Ali Taher, mentorship became real through everyday interactions rather than formal teaching. When he invited Professor Cappellini to Lebanon after first meeting her at the 2005 EHA Congress, he could not have anticipated that the visit would become the beginning of a collaboration and friendship that has now lasted more than two decades.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Their close scientific collaboration began with influential studies such as OPTIMAL CARE, which helped shap","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement activation in immune thrombotic thrombocytopenic purpura: Possible amplifier and potential therapeutic opportunity","authors":"Massimo Cugno,&nbsp;Spero R. Cataland,&nbsp;Bernhard Lämmle","doi":"10.1002/hem3.70508","DOIUrl":"10.1002/hem3.70508","url":null,"abstract":"&lt;p&gt;Immune thrombotic thrombocytopenic purpura (iTTP) is a paradigmatic antibody-mediated thrombotic microangiopathy. Its pathophysiological core is well established: inhibitory and/or clearing autoantibodies against ADAMTS13 cause severe ADAMTS13 deficiency, persistence of ultra-large von Willebrand factor (ULVWF) multimers, platelet adhesion under high shear stress, and platelet-rich microvascular thrombosis.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This model has transformed diagnosis and therapy. Today, acute iTTP is treated with urgent therapeutic plasma exchange, corticosteroids, increasingly early rituximab, and caplacizumab, which blocks the interaction between VWF and platelet glycoprotein Ib.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; With these interventions, targeting the dominant pathogenic axis (autoimmunity against ADAMTS13 and ULVWF-mediated platelet microthrombosis), mortality of acute iTTP has been reduced to below 2%.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Although ADAMTS13 deficiency lies at the center of iTTP pathophysiology, other biological systems that intersect with thromboinflammation may have contributing roles. Complement is one such system. Its activation may amplify endothelial injury, inflammation, renal dysfunction, organ ischemia, and treatment-refractoriness in selected patients. In addition, it has been hypothesized that complement activation could play a role in long-term cardiovascular and neurocognitive complications of iTTP. If this is true, the complement system should be investigated as a component of the thromboinflammatory network that determines phenotype and outcome.&lt;/p&gt;&lt;p&gt;The complement system is increasingly recognized as a bridge between innate immunity, inflammation, endothelial biology, hemostasis, and thrombosis.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Complement activation through the classical, lectin, or alternative pathways converges on C3 cleavage, generation of anaphylatoxins C3a and C5a, opsonization by C3 fragments, and assembly of the terminal complement complex C5b-9. These mediators are not simply antimicrobial effector molecules. C5a can recruit and activate leukocytes, prime neutrophils, and enhance inflammatory tissue injury.&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; Sublytic C5b-9 can activate endothelial cells, increase permeability, and promote prothrombotic responses. Such effects are highly relevant to thrombotic microangiopathies, in which endothelial perturbation and microvascular occlusion are central features.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; There are at least three reasons why complement activation could be relevant in iTTP.&lt;/p&gt;&lt;p&gt;First, ULVWF is not only a platelet-adhesive substrate but can also interact with the complement system. In the microcirculation, high shear stress unfolds VWF and exposes platelet-binding A1 domains, making ULVWF particularly hyperadhesive for platelets. At the same time, endothelial cell-anchored ULVWF strings can assemble and activate components of the alternative complement pathway, providing a plausible mechanistic ","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newly diagnosed and relapsed follicular lymphoma: EHA Clinical Practice Guidelines for diagnosis, treatment, and follow-up","authors":"Marco Ladetto,&nbsp;Natacha Bolaños,&nbsp;Guy Bouguet,&nbsp;Klaus Herfarth,&nbsp;Wolfram Klapper,&nbsp;Sirpa Leppa,&nbsp;Kim Linton,&nbsp;Armando Lopez-Guillermo,&nbsp;Stefano Luminari,&nbsp;Franck Morschhauser,&nbsp;Jessica Okosun,&nbsp;Ewa Paszkiewicz-Kozik,&nbsp;Catherine Thieblemont,&nbsp;Sanne Helene Tonino,&nbsp;Marek Trneny,&nbsp;Judith Trotman,&nbsp;Umut Yilmaz,&nbsp;Martin Dreyling","doi":"10.1002/hem3.70507","DOIUrl":"10.1002/hem3.70507","url":null,"abstract":"<p>Follicular lymphoma (FL) is the second most common lymphoma subtype in Europe, with a median age at diagnosis of 60–65 years. It is generally considered an indolent disease, and the median overall survival at diagnosis now likely exceeds 20 years. However, considerable heterogeneity exists. Diagnosis requires adequate biopsy material and a specialized hematopathologist. Staging and prognosis rely on positron emission tomography (PET)-computed tomography (CT). Prognostication at diagnosis is based on several validated clinical prognostic scores. Localized disease is usually treated with radiotherapy ± Rituximab. The treatment of disseminated disease includes active surveillance (or in selected cases Rituximab monotherapy) for low-tumor burden patients, and most often immunochemotherapy (or in selected cases chemo-free therapeutic options), ±antibody maintenance in high-tumor burden patients. For relapsed or refractory disease, treatment with Rituximab-Lenalidomide combination ± Tafasitamab or Epcoritamab from the first relapse and single-agent bispecific antibodies, chimeric antigen receptor T-cell therapy (CAR-T) cells, and Zanubrutinib-Obinutuzumab after second relapse should be prioritized over immunochemotherapy. Given the long natural history and risk of relapse, careful follow-up is an important part of patient management. Patients should be actively involved in decision-making. In this guideline, we present current evidence-based recommendations for diagnosis, staging, treatment, and follow-up.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No evidence of hypercoagulability, altered fibrinolysis, or increased fibrin(ogen) microaggregates in never-hospitalized long COVID.","authors":"Emily Fraser, Kher Ng, Neda Hasan, Isobel Dunstan, Avianna Laws, Fraser Macrae, Jeries Abu-Hanna, Robert Ariens, Victoria Harris, Jason Oke, Laura Saunders, James Grist, Guilhem Collier, Paul Hughes, Jim Wild, Roger Thompson, Fergus Gleeson, Susan Shapiro","doi":"10.1002/hem3.70501","DOIUrl":"10.1002/hem3.70501","url":null,"abstract":"","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":"e70501"},"PeriodicalIF":11.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149231216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>CEBP</i>-altered B-ALL: Two transcriptomic profiles across the age spectrum.","authors":"Jacqueline A Rehn, Ashlee J Thomson-Roberts, David T Yeung, Deborah L White, Elyse C Page","doi":"10.1002/hem3.70509","DOIUrl":"10.1002/hem3.70509","url":null,"abstract":"","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":"e70509"},"PeriodicalIF":11.3,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“A long bristling road full of adventure, full of discovery” gene therapy approaches in transfusion-dependent thalassemia: The EHA-EBMT consensus paper","authors":"Lucia De Franceschi,&nbsp;Emanuele Angelucci","doi":"10.1002/hem3.70510","DOIUrl":"https://doi.org/10.1002/hem3.70510","url":null,"abstract":"&lt;p&gt;“As you set out for Ithaka&lt;/p&gt;&lt;p&gt;hope your road is a long one,&lt;/p&gt;&lt;p&gt;full of adventure, full of discovery.”&lt;/p&gt;&lt;p&gt;&lt;i&gt;Ithaka&lt;/i&gt; by Kostantinos Kavafis (Greek poet 1863−1933)&lt;/p&gt;&lt;p&gt;Thalassemia, sea (&lt;i&gt;thalassa&lt;/i&gt;, Greek word) and blood (&lt;i&gt;emia&lt;/i&gt;, Greek word), was originally identified in the countries surrounding the Mediterranean Sea. Thalassemia is a globally distributed monogenic red cell disorder, which global burden disease study (GBD) study estimates more than 1,300,000 cases worldwide.&lt;span&gt;&lt;sup&gt;1-3&lt;/sup&gt;&lt;/span&gt; Progress in clinical management of transfusion dependent thalassemic (TDT) patients has improve the prevalence and the mortality, but TDT still negatively impacts patients' quality of life and survival.&lt;span&gt;&lt;sup&gt;1, 4, 5&lt;/sup&gt;&lt;/span&gt; TDT is still largely managed with to the combination of chronic transfusion and iron chelation regimen. Recently, luspatercerpt, an activin ligan trap, and mitapivat, a pyruvate kinases activator, have increased the therapeutic options for TDT.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Up to now the only curative treatments for TDT are allogeneic hemopoietic cell transplantation (HCT) and gene therapy, which was recently approved by both the European Medical Agency (EMA) and the food and drug administration (FDA). In Bone Marrow Transplantation journal, a joint action between the European Hematology Association (EHA) and the European Bone Marrow Transplantation (EBMT) generated a consensus paper on the identification of candidate with TDT for gene therapy.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; This is an update of the European Hematology Association (EHA), Scientific Working Group (SWG) on Red Cells and Iron, in collaboration with the Italian Society of Thalassemia and Hemoglobinopathies (SITE), which was focused on gene addition approach and published in 2021.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; The panel agreed that the large experience achieved and published in allogeneic HCT is the basis for developing the so far most accurate model to define priority criteria to access GT, since currently available GT requires a full myeloablative conditioning regimen and can be considered analogous to an autologous transplantation. Thus, the EHA-EBMT panelists updated and revised the 2021 document discussing: (i) new available treatments; (ii) main data and progress on hematopoietic cell transplantation; (iii) results of clinical studies on both gene addition and gene editing in TDT patients, considering also the available follow-up.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; The risk factors for early death and TDT-related organ complications were also part of the literature revision and the panelists discussion. A special attention was devoted to the impact of organ damage related to the long-term iron cytotoxity. The authors developed a novel flow-chart for TDT patient selection for GT, introducing the central role of liver disease evaluation. This was based on the revision of the literature, the data in HCT and the recent acquisition on long term study in TDT ","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 10","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}