HemaSphere最新文献

{"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}

{"title":"Long-term results of the FIL MCL0208 trial of lenalidomide maintenance versus observation after ASCT in MCL patients","authors":"Rita Tavarozzi,&nbsp;Simone Ferrero,&nbsp;Andrea Evangelista,&nbsp;Elisa Genuardi,&nbsp;Daniela Drandi,&nbsp;Michael Mian,&nbsp;Manuela Zanni,&nbsp;Federica Cavallo,&nbsp;Alice Di Rocco,&nbsp;Vittorio Stefoni,&nbsp;Chiara Pagani,&nbsp;Alessandro Re,&nbsp;Barbara Botto,&nbsp;Monica Balzarotti,&nbsp;Vittorio R. Zilioli,&nbsp;Maria Gomes da Silva,&nbsp;Luca Arcaini,&nbsp;Anna L. Molinari,&nbsp;Filippo Ballerini,&nbsp;Andrés J. M. Ferreri,&nbsp;Benedetta Puccini,&nbsp;Carlo Visco,&nbsp;Piero M. Stefani,&nbsp;Mario Luppi,&nbsp;Ivana Casaroli,&nbsp;Caterina Stelitano,&nbsp;Giovannino Ciccone,&nbsp;Umberto Vitolo,&nbsp;Maurizio Martelli,&nbsp;Sergio Cortelazzo,&nbsp;Marco Ladetto","doi":"10.1002/hem3.70102","DOIUrl":"https://doi.org/10.1002/hem3.70102","url":null,"abstract":"&lt;p&gt;Mantle cell lymphoma (MCL) is an uncommon subtype of B-cell non-Hodgkin lymphoma (NHL) not easily manageable due to chemotherapy resistance and tendency to relapse.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Current treatment for young, fit patients with MCL consists of induction treatment with rituximab and ARA-C-based chemotherapy, followed by consolidation with autologous stem cell transplantation (ASCT) and immunotherapy maintenance.&lt;span&gt;&lt;sup&gt;2-4&lt;/sup&gt;&lt;/span&gt; More recently, the potential value of immunomodulatory agents and Bruton tyrosine kinase inhibitors during induction and maintenance has been investigated, and the role of consolidation ASCT is now debated.&lt;span&gt;&lt;sup&gt;5-7&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The FIL MCL0208 (clinicaltrials.gov no. 02354313) phase III trial evaluated the efficacy of lenalidomide maintenance (LEN) versus observation (OBS) after ASCT in younger, fit patients (18–65 years) with untreated advanced-stage MCL. Further details are provided in Supporting Information. The trial enrolled 303 patients across 38 centers (37 in Italy, 1 in Portugal). At the primary endpoint analysis, with a median follow-up of 38 months, LEN demonstrated a progression-free survival (PFS) benefit but no overall survival (OS) advantage.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Minimal residual disease (MRD) monitoring in peripheral blood (PB) and bone marrow (BM), conducted via nested and real-time PCR (RQ-PCR) at 10 predefined time points, highlighted MRD's prognostic value for time to progression (TTP).&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;This report presents long-term clinical and molecular outcomes with a median follow-up of 74 months, including four additional late MRD assessments at 18, 24, 30, and 36 months, expanding insights into LEN's impact and the prognostic role of MRD over time.&lt;/p&gt;&lt;p&gt;The sample size determination and the statistical plan analyses were described previously.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Further details are provided in Supporting Information.&lt;span&gt;&lt;sup&gt;9, 10&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;From May 4, 2010 to August 24, 2015, a total of 303 patients entered the study. Clinical characteristics at enrollment were published previously.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; The PFS and OS of both the enrolled and randomized populations are described in the original report.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;At the time of the present long-term analysis, the median follow-up was 84 months from enrollment and 73 months for the randomized population. The median PFS of the enrolled population was 64 (95% confidence interval [CI] 56–85) months, and the median OS of the enrolled population was not reached. The 72-month PFS was 48% (95% CI 42–54) and the 72-month OS 75% (95% CI 70–80). At the time of the present long-term analysis, 44 of 104 patients in the LEN arm had a PFS event compared to 51 of 101 patients in the OBS arm. The median PFS from randomization was 76 (95% CI 56-not reached) months in the LEN arm versus 73 (95% CI 46–90) months in the OBS arm. The 72-month PFS rates were 55% (95% CI 44–65)","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 3","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689565","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":"Low-risk MDS—A spotlight on precision medicine for SF3B1-mutated patients","authors":"Shoshana Burke,&nbsp;Onima Chowdhury,&nbsp;Kevin Rouault-Pierre","doi":"10.1002/hem3.70103","DOIUrl":"https://doi.org/10.1002/hem3.70103","url":null,"abstract":"<p>A deep understanding of the biological mechanisms driving the pathogenesis of myelodysplastic neoplasms (MDS) is essential to develop comprehensive therapeutic approaches that will benefit patient's disease management and quality of life. In this review, we focus on MDS harboring mutations in the splicing factor <i>SF3B1</i>. Clones harboring this mutation arise from the most primitive hematopoietic compartment and expand throughout the entire myeloid lineage, exerting distinct effects at various stages of differentiation. Supportive care, particularly managing anemia, remains essential in <i>SF3B1</i>-mutated MDS. While <i>SF3B1</i> mutations are frequently linked with ring sideroblasts and iron overload due to impaired erythropoiesis, the current therapeutic landscape fails to adequately address the underlying disease biology, particularly in transfusion-dependent patients, where further iron overload contributes to increased morbidity and mortality. Novel agents such as Luspatercept and Imetelstat have shown promise, but their availability remains restricted and their long-term efficacy is to be investigated. Spliceosome modulators have failed to deliver and inhibitors of inflammatory pathways, including TLR and NF-κB inhibitors, are still under investigation. This scarcity of effective and disease-modifying therapies highlights the unmet need for new approaches tailored to the molecular and genetic abnormalities in <i>SF3B1</i>-mutated MDS. Emerging strategies targeting metabolic mis-splicing (e.g., <i>COASY</i>) with vitamin B5, pyruvate kinase activators, and inhibitors of oncogenic pathways like MYC and BCL-2 represent potential future avenues for treatment, but their clinical utility remains to be fully explored. The current limitations in treatment underscore the urgency of developing novel, more effective therapies for patients with <i>SF3B1</i>-mutated MDS.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 3","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689455","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":"Brentuximab vedotin monotherapy is a feasible and effective treatment for older patients with classical Hodgkin lymphoma unsuitable for curative chemotherapy: Results from the prospective GHSG–NLG phase II BVB trial","authors":"Alexander Fosså,&nbsp;Daniel Molin,&nbsp;Paul J. Bröckelmann,&nbsp;Gundolf Schneider,&nbsp;Ulf Schnetzke,&nbsp;Johan Linderoth,&nbsp;Peter M. H. Kamper,&nbsp;Sirpa M. Leppä,&nbsp;Julia Meissner,&nbsp;Valdete Schaub,&nbsp;Kjersti Lia,&nbsp;Michael Fuchs,&nbsp;Peter Borchmann,&nbsp;Boris Böll","doi":"10.1002/hem3.70099","DOIUrl":"https://doi.org/10.1002/hem3.70099","url":null,"abstract":"&lt;p&gt;Despite progress over the last decades, the treatment of patients with classical Hodgkin lymphoma (cHL) over the age of 60 years remains challenging.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Biological age, degree of frailty, and severity of underlying diseases may hamper the administration of curative chemotherapy-based approaches developed for younger patients.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; Furthermore, older patients more often have B-symptoms, advanced-stage disease, or other factors known to affect prognosis negatively.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; To improve outcomes for elderly patients with cHL, treatment approaches need to accommodate greater heterogeneity of patients.&lt;/p&gt;&lt;p&gt;In aggressive non-Hodgkin lymphoma (NHL), progress has been made in identifying older patients with impaired health who may need adapted treatment approaches.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Efforts to identify vulnerable older patients are currently also underway for elderly patients with cHL.&lt;span&gt;&lt;sup&gt;1, 3&lt;/sup&gt;&lt;/span&gt; Meanwhile, novel drugs hold promise as effective and better-tolerated options compared to traditional chemotherapy in older individuals.&lt;span&gt;&lt;sup&gt;1, 5&lt;/sup&gt;&lt;/span&gt; The antibody-drug conjugate brentuximab vedotin (BV) contains the tubulin-acting drug monomethyl auristatin E and targets CD30 expressing malignant Hodgkin and Reed&lt;i&gt;–&lt;/i&gt;Sternberg cell characteristic of cHL. Single-agent BV has relatively low toxicity with neuropathy being a common dose-limiting adverse effect, and is also tolerated by relapsed or refractory cHL patients over the age of 60 years.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;We started a prospective phase II trial in 2015, evaluating single-agent BV in patients considered unsuitable for available curative combination chemotherapy. The BVB trial (BV or BV with cyclophosphamide, doxorubicin, and prednisolone in the treatment of older patients with newly diagnosed cHL) was an international two-armed open-label intergroup multicentre phase II trial by the German Hodgkin Study Group (GHSG) and the Nordic Lymphoma Group (NLG) (NCT02191930). The main inclusion criteria were histologically proven cHL, no previous treatment, and age ≥60 years. Patients at any stage were eligible for BV monotherapy if scored ≥7 by the cumulative illness rating scale for geriatrics (CIRS-G) or not considered candidates for curative combination chemotherapy at the investigator's judgment irrespective of performance status. Patients with pre-existing peripheral neuropathy grade ≥1 were excluded. Staging of cHL was done with contrast-enhanced computed tomography (CT) from neck to pelvis and bone marrow biopsy (Supporting Methods). All patients gave written informed consent.&lt;/p&gt;&lt;p&gt;BV was administered intravenously every 3 weeks at 1.8 mg/kg (maximum 180 mg) for up to 16 cycles. The response was assessed with CT after two and six cycles and at the end of therapy. Fluorodeoxyglucose positron emission tomography with CT (PET-CT) was not mandatory at diagnosis or response evaluation. The primar","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 3","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689456","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":"Ibrutinib, lenalidomide, and rituximab in relapsed mantle cell lymphoma: Long-term follow-up of the Nordic Lymphoma Group MCL6 Philemon trial","authors":"Elin Forsgren,&nbsp;Rasmus R. K. Jørgensen,&nbsp;Hans Bentzen,&nbsp;Jon Riise,&nbsp;Jacob Haaber,&nbsp;Annika Pasanen,&nbsp;Hanne Kuitunen,&nbsp;Karin F. Wader,&nbsp;Tarec C. El-Galaly,&nbsp;Martin Hutchings,&nbsp;Ingrid Glimelius,&nbsp;Mats Jerkeman","doi":"10.1002/hem3.70101","DOIUrl":"https://doi.org/10.1002/hem3.70101","url":null,"abstract":"<p>Relapsed or refractory mantle cell lymphoma (R/R MCL) remains difficult to treat, with outcomes dependent on the treatment regimen and remission duration after first-line therapy. Several non-chemotherapeutic regimens are under evaluation in R/R, but few studies report long-term outcomes. In this study, we present the long-term outcomes of the 50 patients treated with ibrutinib, lenalidomide, and rituximab (IR2) in the Nordic Lymphoma Group MCL6 Philemon phase 2 trial. Survival outcomes were compared with a matched cohort from the Swedish MCL<i>complete</i> study. After 5 years, 14 patients (28%) remained relapse-free, including one with a <i>TP53</i> mutation. The median progression-free survival (PFS) was 17.4 months, with the longest PFS of 8.1 years. Thirty-two patients had died, primarily from MCL (72%). Poorer survival was associated with intermediate or high-risk Mantle Cell Lymphoma International Prognostic Index and impaired health-related quality of life (HRQoL). While <i>TP53</i> mutations (<i>n</i> = 11) did not significantly impact survival, a trend toward poorer outcomes was observed in multivariable Cox regression analyses (PFS hazard ratio: 2.09, 95% confidence interval: 0.95–4.62, <i>p</i> = 0.068). The IR2 regimen demonstrated superior survival compared to the MCL<i>complete</i> cohort both before and after matching. In conclusion, this study highlights the role of non-chemotherapeutic agents in R/R MCL and demonstrates the prognostic impact of HRQoL on overall survival. Although IR2 showed initial activity in TP53-mutated patients, it did not completely overcome their poor prognosis. However, the IR2 regimen may serve as a bridge to allogeneic stem cell transplantation or chimeric antigen receptor T-cell therapy.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 3","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638913","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}