HemaSphere最新文献

{"title":"High-dose therapy followed by autologous stem cell transplantation emerges as the preferred salvage therapy in patients with limited-stage Hodgkin lymphoma progressing/relapsing after initial therapy: A subset analysis of the EORTC/LYSA/FIL H10 trial","authors":"Gotti Manuel, Yana Stepanishyna, Tetiana Skrypets, Luigi Marcheselli, Caterina Cristinelli, Barbara Botto, Sanne Tonino, Doriane Cavalieri, Alessandro Pulsoni, Martin Hutchings, Mohammad Hammoud, Catherine Fortpied, Luigi Rigacci, Wouter Plattel, Marc André, Massimo Federico","doi":"10.1002/hem3.70105","DOIUrl":"https://doi.org/10.1002/hem3.70105","url":null,"abstract":"<p>Long-term survival of patients with limited-stage classical Hodgkin lymphoma (cHL) is excellent, with more than 90% surviving and disease-free for 10 years after diagnosis and initial treatment.<span><sup>1, 2</sup></span> Nevertheless, improving patient outcomes and minimizing the risk of long-term toxicities continue to be priorities.</p><p>Early response assessment with positron emission tomography (ePET) is an important predictor of outcomes, and several trials have focused on response-adapted treatments to avoid the need for radiotherapy (RT) in patients with an early complete metabolic response. In the EORTC/LYSA/FIL H10 intergroup randomized trial, such a response-adapted strategy resulted in the achievement of 95% overall survival at 10 years.<span><sup>1</sup></span> However, in the 1419 cases with updated follow-up, 106 progressions or recurrences (7.5%) were recorded.</p><p>In this study, we report the results of a detailed analysis of second-line treatment choices and outcomes in these 106 patients. Previously untreated patients aged 15–70 years with classic supradiaphragmatic stage I or II cHL were eligible for the EORTC/LYSA/FIL H10 trial. Both favorable (F) and unfavorable (U) patients according to the EORTC criteria were included. All patients received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), after which an ePET was performed. The primary objective of this study was to evaluate whether involved-node RT could be omitted without loss of efficacy in ePET-negative patients.<span><sup>2</sup></span> This long-term analysis was restricted to the subset of patients with progression/recurrence after study entry. The principal endpoints of this analysis were survival after recurrence (SAR) and progression-free survival after recurrence (PFS2). From November 2006 to June 2011, 1950 patients were enrolled in the EORTC/LYSA/FIL H10 trial by 158 institutions, in which 1925 completed two ABVD cycles and performed an ePET scan. Long-term follow-up has been updated for 1419 of these patients (Supporting Information S3: Data Supplement Figure 1).</p><p>Overall, 106 (7.5%) events were recorded, including 17 progressions (events within 6 months from study entry, 1.2%) and 89 recurrences (6.3%). Ninety-five events occurred in this study population before the safety amendment, and 11 thereafter. Patients' characteristics and outcomes for the entire cohort are summarized in Table 1.</p><p>Events occurred in 5.5% (28/508), 6.5% (42/651), and 13.8% (36/260) of patients with early favorable ePET-, early unfavorable ePET-, and ePET-positive disease, respectively.</p><p>Sites of progression/recurrence were recorded in 32 (30.2%) patients with initially involved and non-irradiated sites, 12 (11.3%) involved and irradiated, 45 (42.4%) not initially involved and not irradiated, and 17 (16.0%) not involved but irradiated sites. The 17 progressions occurred after a median of 4.4 months from study entry (range 2.1–6.0 months).","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749454","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":"H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia","authors":"Vera H. Jepsen,&nbsp;Andrea Hanel,&nbsp;Daniel Picard,&nbsp;Rigveda Bhave,&nbsp;Rebecca Hasselmann,&nbsp;Juha Mehtonen,&nbsp;Julian Schliehe-Diecks,&nbsp;Carla-Johanna Kath,&nbsp;Vithusan Suppiyar,&nbsp;Yash Prasad,&nbsp;Katerina Schaal,&nbsp;Jia-Wey Tu,&nbsp;Nadine Rüchel,&nbsp;Ersen Kameri,&nbsp;Nan Qin,&nbsp;Herui Wang,&nbsp;Zhengping Zhuang,&nbsp;Rabea Wagener,&nbsp;Lena Blümel,&nbsp;Tobias Lautwein,&nbsp;Daniel Hein,&nbsp;David Koppstein,&nbsp;Gesine Kögler,&nbsp;Marc Remke,&nbsp;Sanil Bhatia,&nbsp;Merja Heinäniemi,&nbsp;Arndt Borkhardt,&nbsp;Ute Fischer","doi":"10.1002/hem3.70116","DOIUrl":"https://doi.org/10.1002/hem3.70116","url":null,"abstract":"<p><i>ETV6::RUNX1</i>, the most common oncogenic fusion in pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL), induces a clinically silent preleukemic state that can persist in carriers for over a decade and may progress to overt leukemia upon acquisition of secondary lesions. The mechanisms contributing to quiescence of <i>ETV6::RUNX1</i>+ preleukemic cells still remain elusive. In this study, we identify linker histone H1-0 as a critical mediator of the <i>ETV6::RUNX1</i>+ preleukemic state by employing human\u0000<span>-</span>induced pluripotent stem cell (hiPSC) models engineered by using CRISPR/Cas9 gene editing. Global gene expression analysis revealed upregulation of <i>H1-0</i> in <i>ETV6::RUNX1</i>+ hiPSCs that was preserved upon hematopoietic differentiation. Moreover, whole transcriptome data of 1,727 leukemia patient samples showed significantly elevated <i>H1-0</i> levels in <i>ETV6::RUNX1</i>+ BCP-ALL compared to other leukemia entities. Using dual-luciferase promoter assays, we show that ETV6::RUNX1 induces <i>H1-0</i> promoter activity. We further demonstrate that depletion of H1-0 specifically inhibits ETV6::RUNX1 signature genes, including <i>RAG1</i> and <i>EPOR</i>. Single-cell sequencing showed that <i>H1-0</i> is highly expressed in quiescent hematopoietic cells. Importantly, H1-0 protein levels correspond to susceptibility of BCP-ALL cells towards histone deacetylase inhibitors (HDACis) and combinatorial treatment using the H1-0-inducing HDACi Quisinostat showed promising synergism with established chemotherapeutic drugs. Taken together, our data identify H1-0 as a key regulator of the <i>ETV6::RUNX1</i>+ transcriptome and indicate that the addition of Quisinostat may be beneficial to target non-responsive or relapsing <i>ETV6::RUNX1</i>+ BCP-ALL.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749453","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":"TP53 deletion as an MRD-dependent risk factor in childhood B-ALL: A post hoc analysis from a prospective cohort","authors":"Yangyang Gao,&nbsp;Jun Li,&nbsp;Ning Wang,&nbsp;Wenbin An,&nbsp;Zixi Yin,&nbsp;Junxia Wang,&nbsp;Xia Chen,&nbsp;Yumei Chen,&nbsp;Ye Guo,&nbsp;Wenyu Yang,&nbsp;Li Zhang,&nbsp;Yao Zou,&nbsp;Xiaojuan Chen,&nbsp;Xiaofan Zhu","doi":"10.1002/hem3.70115","DOIUrl":"https://doi.org/10.1002/hem3.70115","url":null,"abstract":"<p>The effect of <i>TP53</i> alterations on childhood B-cell acute lymphoblastic leukemia (B-ALL) remains unclear. To investigate the prognostic value of <i>TP53</i> deletion (<i>TP53</i>^<i>del</i>) and <i>TP53</i> mutation (<i>TP53</i>^<i>mut</i>), this post hoc study used fluorescence in situ hybridization test to detect <i>TP53</i>^<i>del</i> in 907 newly diagnosed B-ALL patients from a prospective cohort of Chinese Children's Cancer Group ALL-2015 trial. Targeted gene sequencing was used to identify <i>TP53</i>^<i>mut</i> in 342 out of the 907 patients. <i>TP53</i>^<i>del</i> was detected in 4.4% of patients. The frequency of hypodiploidy was higher in <i>TP53</i>^<i>del</i> subgroup (7.5% vs. 0.5%, <i>p</i> = 0.002), but patients with <i>TP53</i>^<i>del</i> were less likely to have other recurrent genetic abnormalities, including <i>BCR::ABL1, ETV6::RUNX1, TCF3::PBX1 and KMT2A</i> rearrangements. Univariable and multivariable analyses indicated that <i>TP53</i>^<i>del</i> was an independent risk factor for overall survival (OS) and disease-free survival (DFS). Furthermore, stratification analysis revealed that <i>TP53</i>^<i>del</i> was associated with lower 5-year DFS in patients with positive minimal residual disease (MRD) after induction in the intermediate-risk group (0.0% vs. 58.0% [95% confidence interval [CI] 49.2%–68.3%], <i>p</i> &lt; 0.001), suggesting an MRD-dependent pattern. However, somatic <i>TP53</i>^<i>mut</i> was not associated with poor survival (81.8% [95% CI 61.9%–100.0%] vs. 84.9% [95% CI 81.1%-89.0%], <i>p</i> = 0.971). In summary, <i>TP53</i>^<i>del</i> may serve as a predictor for poor prognosis in pediatric B-ALL. In particular, children in the intermediate-risk group with positive MRD and <i>TP53</i>^<i>del</i> may require more aggressive treatment.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741648","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":"European Cancer Organisation Essential Requirements for Quality Cancer Care: Hematological malignancies","authors":"John G. Gribben,&nbsp;Leticia Quintanilla-Martinez,&nbsp;Simon Crompton,&nbsp;Jann Arends,&nbsp;Christophe Bardin,&nbsp;Heiko Becker,&nbsp;Frederic Castinetti,&nbsp;Dégi L. Csaba,&nbsp;Melvin D'Anastasi,&nbsp;Thomas Frese,&nbsp;Jan Geissler,&nbsp;Reda Matuzeviciene,&nbsp;Marius E. Mayerhoefer,&nbsp;Rui Medeiros,&nbsp;Kate Morgan,&nbsp;Šarūnas Narbutas,&nbsp;Samantha Nier,&nbsp;Umberto Ricardi,&nbsp;Eugenia Trigoso Arjona,&nbsp;Mehmet Ungan,&nbsp;Lorna Warwick,&nbsp;Emanuele Zucca","doi":"10.1002/hem3.70108","DOIUrl":"https://doi.org/10.1002/hem3.70108","url":null,"abstract":"&lt;p&gt;European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCCs) are primarily organizational recommendations, giving politicians, managers, oncology teams, patients, and patient advocacy groups a non-technical overview of the elements needed to provide high-quality care throughout the patient journey. They are not clinical guidelines, but define the actions necessary to deliver high-quality care to patients with specific cancer types, here applied to hematological malignancies in Europe.&lt;/p&gt;&lt;p&gt;The recommendations set out an aspirational but realistic standard that should be within reach for most countries, given adequate resourcing. They include the need for (1) fast and easy access to accurate diagnostic tests; (2) clearly established pathways for referral to specialist centers; (3) services to be centralized; (4) continuous monitoring of patient well-being; (5) treatment strategies to be agreed by a core multidisciplinary team; and (6) patients and their families to be involved at all stages of decision-making.&lt;/p&gt;&lt;p&gt;The foundation of ERQCCs is quality. This has become increasingly important in all aspects of healthcare as new and complex treatments come into use and pressure grows on resources. Improving quality means delivering cancer care that is timely, safe, effective, and efficient; that puts the patient at the center; and that gives all people in Europe equal access to high-quality services.&lt;/p&gt;&lt;p&gt;Variations in cancer outcomes and disparities in management and funding across Europe make quality frameworks essential.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The European Guide on Quality Improvement in Comprehensive Cancer Control (2017) underscored this fact, recommending comprehensive cancer centers and integrated care networks.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; However, while some progress has been made in concentrating expertise for specific tumor types such as breast and prostate cancers, dedicated multidisciplinary units are lacking for most cancers, including hematological malignancies. Recent initiatives such as Europe's Beating Cancer Plan have added a new momentum to quality initiatives, emphasizing multidisciplinary collaboration and timely access to quality treatment, aligning closely with ERQCC principles.&lt;/p&gt;&lt;p&gt;Hematological malignancies (blood cancers) are the fifth most common cancer group in economically developed regions. They include leukemias, lymphomas, and myelomas, with over 100 clinically meaningful subtypes defined by the World Health Organization's Classification of Tumours of Haematopoietic and Lymphoid Tissues and the International Consensus Classification.&lt;span&gt;&lt;sup&gt;3-6&lt;/sup&gt;&lt;/span&gt; The European Society for Medical Oncology (ESMO) and the European Hematology Association (EHA) have issued clinical practice guidelines for many of the subtypes and these are regularly updated.&lt;/p&gt;&lt;p&gt;The European-Commission-funded HAEMACARE project has produced crude, age-specific, and age-standardized incidence rates for hematologic","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 4","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741649","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":"Two distinct fetal-type signatures characterize juvenile myelomonocytic leukemia","authors":"Marion Strullu,&nbsp;Chloé Arfeuille,&nbsp;Aurélie Caye-Eude,&nbsp;Loïc Maillard,&nbsp;Elodie Lainey,&nbsp;Florian Piques,&nbsp;Bruno Cassinat,&nbsp;Fabien Guimiot,&nbsp;Jean-Hugues Dalle,&nbsp;André Baruchel,&nbsp;Christine Chomienne,&nbsp;Dominique Bonnet,&nbsp;Michèle Souyri,&nbsp;Hélène Cavé","doi":"10.1002/hem3.70104","DOIUrl":"https://doi.org/10.1002/hem3.70104","url":null,"abstract":"<p>Juvenile myelomonocytic leukemia (JMML) is an aggressive clonal myeloproliferative neoplasm that affects infants and young children. The narrow window of onset suggests that age-related factors are involved in leukemogenesis. To investigate whether ontogeny-related features are involved in JMML oncogenesis, we compared the gene expression profile of hematopoietic progenitor cells isolated from JMML patients with that of healthy individuals at different stages of ontogeny. This analysis identified two main groups of JMML patients. In the first group, JMML progenitors exhibited a gene expression profile similar to that of embryo-fetal progenitors. Progenitors showed a strong monocytic identity as evidenced by the overexpression of monocytic/dendritic, inflammasome, and innate immune markers. This resembled the monocyte-predominant myelopoiesis characteristic of normal fetal hematopoiesis. However, in the second group, despite evidence of developmental dysregulation as indicated by the aberrant signature of the master oncofetal regulator LIN28B, JMML clustered separately from healthy prenatal and postnatal fractions. These findings highlight the intricate relationship between JMML and development, which will help inform future therapeutic approaches for this rare but severe form of leukemia.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 3","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690198","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":"Mild or moderate hemophilia is not always a mild or moderate bleeding disorder: Back to the clinical phenotype","authors":"Francesco Rodeghiero,&nbsp;Lisanna Ghiotto,&nbsp;Luca Pontalto,&nbsp;Alessandro Casini,&nbsp;Giancarlo Castaman,&nbsp;Rezan Abdul-Kadir,&nbsp;Erik Berntorp,&nbsp;Imre Bodó,&nbsp;Manon Degenaar-Dujardin,&nbsp;Karin Fijnvandraat,&nbsp;Paolo Gresele,&nbsp;Nigel S. Key,&nbsp;Riitta Lassila,&nbsp;Frank W. G. Leebeek,&nbsp;David Lillicrap,&nbsp;Mike Makris,&nbsp;Stephan Meijer,&nbsp;Diego Mezzano,&nbsp;Patrizia Noris,&nbsp;Ingrid Pabinger,&nbsp;Margaret V. Ragni,&nbsp;David Silva,&nbsp;Alok Srivastava,&nbsp;Alberto Tosetto,&nbsp;Jerzy Windyga,&nbsp;Barbara Zieger","doi":"10.1002/hem3.70111","DOIUrl":"https://doi.org/10.1002/hem3.70111","url":null,"abstract":"<p>In a previous paper, a comprehensive clinicopathologic approach to mild and moderate bleeding disorders (MBD) was proposed by an international working group (IWG) as a part of a project promoted by the European Hematology Association (EHA) on the development of guidelines on the various MBDs. A single pre-diagnosis grade 4 bleeding event according to the ISTH-BAT scale or a comparable event after diagnosis was considered sufficient to classify a patient as affected by a severe bleeding disorder (SBD). In this article, the original IWG integrated by experts and patients' representatives proposed by the European Haemophilia Consortium (EHC) and European Association of Haemophilia and Allied Disorders (EAHAD) applied these criteria to mild and moderate hemophilia A and B to establish the proportion of cases that would be reclassified as SBD taking into account bleeding phenotype, thus improving over the current classification based exclusively on basal factor VIII or IX level. To this aim, publications of unselected cases with bleeding history available from birth to the time of publication were considered to estimate the incidence of a first severe bleeding event. More than 20% of cases with mild or moderate hemophilia met the criteria for SBD by experiencing joint or non-joint severe bleeding events. Furthermore, a significant proportion of patients developed an inhibitor against factor VIII or IX. These results, based on a rigorous methodologic approach, substantiate the criticism of the current classification of hemophilia and argue for the adoption of a new classification that takes into account bleeding phenotype in addition to basal clotting activity.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 3","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690197","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":"Changes in the quality of life of adults with sickle cell disease following allogeneic stem cell transplantation: A mixed-methods, prospective cohort study","authors":"Elisabeth Dovern,&nbsp;Sterre J. A. M. Nijland,&nbsp;Annemarie M. J. Braamse,&nbsp;Maud M. van Muilekom,&nbsp;Elisabeth M. J. Suijk,&nbsp;Gerianne M. Hoogendoorn,&nbsp;Charlotte F. J. van Tuijn,&nbsp;Michael R. DeBaun,&nbsp;Bart J. Biemond,&nbsp;Lotte Haverman,&nbsp;Erfan Nur","doi":"10.1002/hem3.70100","DOIUrl":"https://doi.org/10.1002/hem3.70100","url":null,"abstract":"<p>Advances in conditioning regimens have made non-myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) a viable curative option for adults with sickle cell disease (SCD). However, prospective studies comparing pre- and post-transplant patient-reported health outcomes are scarce. Therefore, in a prospective, mixed-methods cohort study in adults with SCD undergoing HSCT, we tested the hypothesis that physical, mental, and social health improves after HSCT relative to baseline. We compared 9 Patient-Reported Outcomes Measurement Information System (PROMIS®) measures at 6, 12, and 18 months post-transplant to baseline and general population values. Semi-structured interviews were conducted pre- and post-transplant that were thematically analyzed (MAXQDA). Seventeen patients (7 females, 10 males; median age 26 years) underwent matched sibling (9) or haploidentical donor (8) transplantation. Compared to baseline, pain interference (<i>p</i> = 0.008), physical function (<i>p</i> &lt; 0.001), fatigue (<i>p</i> = 0.001), anxiety (<i>p</i> = 0.016), anger (<i>p</i> = 0.037), and the ability to (<i>p</i> &lt; 0.001) and satisfaction with (<i>p</i> &lt; 0.001) social roles and activities improved at 18 months. Compared to reference values, physical function, sleep disturbance, fatigue, anxiety, and the ability to and satisfaction with social roles and activities <i>T</i>-scores were significantly worse at baseline but comparable or better after 18 months. Thematic analysis of the interviews revealed high satisfaction with improved physical and social abilities alongside complex mental health challenges, including processing the psychological aftermath of SCD, dealing with transplant-related toxicity, adjustment challenges, and identity conflicts. In conclusion, while physical, mental, and social health improves after HSCT, the effects on mental health can be complex and warrant psychosocial support early in the process of curative therapies.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 3","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689918","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":"Daratumumab-based regimens versus CyBorD in newly diagnosed patients with AL amyloidosis and IIIb cardiac stage: A matched case-control study","authors":"Claudia Bellofiore,&nbsp;Marco Basset,&nbsp;Giuseppe Damiano Sanna,&nbsp;Andrea Foli,&nbsp;Roberta Mussinelli,&nbsp;Martina Nanci,&nbsp;Alessandro Fogliani,&nbsp;Martina Ciardo,&nbsp;Mario Nuvolone,&nbsp;Giampaolo Merlini,&nbsp;Giovanni Palladini,&nbsp;Paolo Milani","doi":"10.1002/hem3.70112","DOIUrl":"https://doi.org/10.1002/hem3.70112","url":null,"abstract":"&lt;p&gt;Immunoglobulin light chain (AL) amyloidosis is a life-threatening systemic disease especially when the heart is severely affected.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The pathogenic mechanism relies on the production, by a B-cell clone, of immunoglobulin free light chains (FLC), which form fibrillar structures that deposit in organs and tissues and exert cardiac toxicity.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The heart is the most frequently affected organ and is the major determinant of clinical outcome.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The current prognostic cardiac staging system stratifies patients' survival using two biomarkers: troponins and B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP).&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; Approximately 20% of patients present with advanced heart involvement, classified as IIIb cardiac stage. These patients have a dismal survival&lt;span&gt;&lt;sup&gt;3, 5&lt;/sup&gt;&lt;/span&gt; that has not improved in recent years.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The standard frontline treatment for AL amyloidosis has been bortezomib in combination with dexamethasone and alkylating agents (i.e., cyclophosphamide [CyBorD]&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; or melphalan)&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; until the approval of daratumumab in combination with CyBorD (Dara-CyBorD) in 2021, which significantly improved the rate and depth of hematologic response, as well as overall survival (OS), as reported by the ANDROMEDA trial.&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt; However, stage IIIb patients were excluded from the pivotal study and the best upfront treatment strategy for these patients remains to be clarified. For this reason, daratumumab was not licensed for use in stage IIIb patients in Europe. Nevertheless, the European Hematology Association and International Society of Amyloidosis (EHA-ISA) working group guidelines recommend, where feasible, the use of daratumumab, even as monotherapy, in stage IIIb patients based on the encouraging preliminary data of the EMN22 phase II multicenter study (NCT04131309).&lt;span&gt;&lt;sup&gt;9, 10&lt;/sup&gt;&lt;/span&gt; Several retrospective series have evaluated daratumumab-containing regimens in treatment-naïve stage IIIb patients reporting promising results.&lt;span&gt;&lt;sup&gt;11, 12&lt;/sup&gt;&lt;/span&gt; However, all available data on daratumumab in this high-risk population derive from uncontrolled studies, and head-to-head comparative data remain limited. The only comparative study to date, conducted by Oubari et al.,&lt;span&gt;&lt;sup&gt;13&lt;/sup&gt;&lt;/span&gt; matched patients solely by disease stage, underscoring the need for further comparative studies to evaluate the effectiveness of daratumumab in this setting.&lt;/p&gt;&lt;p&gt;We designed the present retrospective case-control study to assess the efficacy of daratumumab-based therapies versus CyBorD as an upfront treatment for newly diagnosed AL amyloidosis with IIIb cardiac stage. The prospectively maintained databases of the Amyloidosis Research and Treatment Center of Pavia were searched for newly diagnosed patients with systemic AL amyloidosis and IIIb cardiac","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 3","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689917","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":"Patient and physician perceptions regarding treatment expectations and symptomatology in polycythemia vera: Insights from the Landmark 2.0 global health survey","authors":"Claire N. Harrison,&nbsp;David M. Ross,&nbsp;Laura Maria Fogliatto,&nbsp;Lynda Foltz,&nbsp;Lambert Busque,&nbsp;Zhijian Xiao,&nbsp;Florian H. Heidel,&nbsp;Michael Koehler,&nbsp;Giuseppe A. Palumbo,&nbsp;Massimo Breccia,&nbsp;Norio Komatsu,&nbsp;Keita Kirito,&nbsp;Blanca Xicoy Cirici,&nbsp;Joaquin Martinez-Lopez,&nbsp;Alicia Rovo,&nbsp;Cheryl Petruk,&nbsp;Catalin Bobirca,&nbsp;Laura Mirams,&nbsp;Abigail McMillan,&nbsp;Gavin Harper,&nbsp;Jean-Jacques Kiladjian","doi":"10.1002/hem3.70106","DOIUrl":"https://doi.org/10.1002/hem3.70106","url":null,"abstract":"<p>Polycythemia vera (PV) is a myeloproliferative neoplasm associated with a high symptom and psychological burden, resulting in decreased quality of life (QoL). Patients with PV have an increased risk of cardiovascular (CV) complications, making regular monitoring crucial. The Landmark 2.0 survey was conducted worldwide among patients with PV and their treating physicians to identify any potential gaps in perceptions regarding PV management. Data were collected between April 2021 and April 2022 from physicians and patients across 11 countries. Overall, 133 physicians and 274 patients with PV participated in the survey. There were discrepancies between physicians and patients in reporting whether symptom assessments and basic CV assessments were conducted during routine visits (83% vs. 68% and 64% vs. 55%, respectively). Emotional assessments were not performed routinely (reported by 36% of physicians and 34% of patients). Patients attributed the highest impact on QoL to physical symptoms (67%); however, physicians were less likely to report highly prevalent symptoms such as bruising, difficulty sleeping, inactivity, and depression among the most common symptoms. While both physicians and patients aimed for symptom improvement, their treatment goals differed: physicians focused on managing hematocrit, preventing thrombotic events, and reducing spleen size, while patients focused on slowing down disease progression. Patient satisfaction with treatment was generally high but decreased in later therapy stages. Overall, these data underscore the disparity in patient–physician perceptions of PV management and treatment expectations, showing the gaps in communication and the need for greater patient education, as well as highlighting areas for potential improvement in clinical practice.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 3","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689915","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":"Chimeric antigen receptor T-cell therapy in diffuse large B-cell lymphoma: Evaluating axicabtagene ciloleucel in the ZUMA-7 trial","authors":"Vadim Lesan,&nbsp;Cristian Munteanu","doi":"10.1002/hem3.70119","DOIUrl":"https://doi.org/10.1002/hem3.70119","url":null,"abstract":"&lt;p&gt;Chimeric antigen T-cell (CAR-T) therapy is the new standard of therapy in patients with refractory or early relapsed diffuse large B-cell lymphoma (r/r DLBCL).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Axicabtagene ciloleucel (Axi-cel) was one of the first therapies to show superior event free survival (primary endpoint of the study) and significant overall survival (OS) benefit in this context.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Recently published data on subsequent anti-lymphoma therapies after second-line axicabtagene ciloleucel (Axi-Cel) imply that outcomes are better when Axicel is given in earlier lines of therapies.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Further, reanalysis of the ZUMA-7 trial outcome data regarding the metabolic tumor volume (MTV) revealed that Axicel improved event-free survival and progression-free survival over the standard of care irrespective of MTV.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Although we acknowledge the positive impact of Axicel in the treatment of patients with DLBCL, we raise some concerns about moving Axicel further in the frontline therapies.&lt;/p&gt;&lt;p&gt;Analyzing the outcome results for subsequent therapies after Axi-cel and SOC in the context of the previous reports from the ZUMA-7 trial, we observed some important discrepancies. First, the median time to third-line therapy was lower in the SOC arm compared to the Axi-Cel arm (2.8 vs. 4.4 months). This difference could be either due to higher proportion of aggressive disease and/or poor prognostic factors in SOC arm or due to greater investigator's willingness to declare refractory and/or progressive disease in the SOC arm compared to Axi-Cel arm. Although, the absence of bridging therapy has precluded the enrollment of patients with aggressive disease in the initial report of the ZUMA-7 trial, only two patients had progressive disease before Axi-Cel infusion. At a median of 29 days from leukapheresis to infusion without bridging therapy, this results in a progression rate of 0.06 patients per day. On the other side, seventy patients progressed in the SOC arm before autologous stem cell transplantation (ASCT). Since data on the duration between the start of the salvage chemotherapy and ASCT was not reported, estimating it at about 60 days (corresponding to two cycles of salvage chemotherapy at a duration of 21 days per cycle and adding time for leukapheresis and pre-ASCT screening) will result in a progression rate of 1.1 patients per day. Altogether, these results point to a higher proportion of aggressive disease in the SOC arm and potential survivorship bias in the Axi-Cel arm. The role of investigator's willingness to declare more refractory and/or progressive disease in the SOC arm should be minimal, since the responses in the initial report were assessed per-blinded central review. Still, ZUMA-7 is an open-label study, and assessment bias might have occurred. Blinded outcome assessment alone is not sufficient to overcome the information bias upon which the response assessment is based.&lt;span&gt;&lt;sup&gt;5&lt;/","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 3","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689916","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}