European Journal of Haematology最新文献

{"title":"Relevance, Risks, and Benefits of Early-Phases Clinical Trials Participations for Patients With Hematological Malignancies From 2008 to 2023","authors":"Matteo Guerra,&nbsp;Emily Alouani,&nbsp;Thomas Hueso,&nbsp;Kaissa Ouali,&nbsp;Alina Danu,&nbsp;Antoine Hollebecque,&nbsp;Rastislav Bahleda,&nbsp;Christophe Willekens,&nbsp;Anas Gazzah,&nbsp;Capucine Baldini,&nbsp;Sophie Postel-Vinay,&nbsp;Jean-Baptiste Micol,&nbsp;Christophe Massard,&nbsp;Stéphane De Botton,&nbsp;Vincent Ribrag,&nbsp;Jean-Marie Michot","doi":"10.1111/ejh.14307","DOIUrl":"10.1111/ejh.14307","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Early-phases clinical trials (Phases 1 and 2) have evolved from a traditional assessment of toxicity to an adaptive approach based on patients' medical needs and access to effective new therapies. The global risks, benefits, and relevance of early-phases clinical trials participation for patients with hematological malignancies remain poorly evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>All early-phases clinical trials participations for patients with hematological malignancies, from 2008 to 2023, in a tertiary academic center in Europe, were reviewed. Patient's demographics, tumor type categories, therapeutic responses, mortality, overall survival (OS), and investigational product (IP) were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over the period 2008–2023, 736 patients participating in 92 different early-phases clinical trials, were analyzed. The most common tumor categories were diffuse large B-cell lymphoma (<i>n</i> = 253; 34.4%), acute myeloid leukemia/myelodysplastic syndrome (<i>n</i> = 164; 22.3%) and multiple myeloma (<i>n</i> = 100; 13.6%). The median OS was 14.8 (95% CI: 12.4–17.9) months and response rate 31.9%, including complete responses in 13.5% of patients. By tumor categories, the highest and lowest median duration of OS were observed for patients with Hodgkin lymphoma (99.8; [95% CI: 47.0-not reached] months) and peripheral T-cell lymphoma (8.9 [95% CI: 5.3–12.0] months), respectively. The on-protocol and treatment-related mortality rates were 5.43% and 0.54%, respectively. Overall response rate was 29.1% including 13.5% of complete response. Overall, 202 (27.5%) patients received an IP later approved by the health authorities, and those patients had better OS (18.2 months vs. 12.1 months HR: 1.160 [95% CI; 0.6977–1.391], <i>p</i> = 0.0283).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, patients with hematologic malignancies who have participated in early-phases clinical trials over the past 15 years have achieved variable therapeutic response rates, acceptable risk/benefit ratio and potentially significant therapeutic advantages. This study provides framework material for hematologists to further discuss clinical trial participation with their patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"89-97"},"PeriodicalIF":2.3,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparable Results Between 8 and 12 Gray TBI in Combination With Fludarabine and Post-Transplant Cyclophosphamide in MRD-Negative but Not in MRD-Positive Acute Lymphoblastic Leukemia Patients Transplanted in First Complete Remission","authors":"Normann Steiner,&nbsp;Radwan Massoud,&nbsp;Johanna Richter,&nbsp;Tetiana Perekhrestenko,&nbsp;Nico Gagelmann,&nbsp;Christian Niederwieser,&nbsp;Kristin Rathje,&nbsp;Iryna Lastovytska,&nbsp;Mathias Schäfersküpper,&nbsp;Silke Heidenreich,&nbsp;Ina Rudolph,&nbsp;Gaby Zeck,&nbsp;Dietlinde Janson,&nbsp;Christine Wolschke,&nbsp;Francis Ayuketang Ayuk,&nbsp;Evgeny Klyuchnikov,&nbsp;Nicolaus Kröger","doi":"10.1111/ejh.14305","DOIUrl":"10.1111/ejh.14305","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The optimal TBI dose for ALL patients undergoing allogeneic SCT is still not clearly defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-center retrospective analysis of high-risk ALL patients in CR1 treated with 8 Gy (<i>n</i> = 22) or 12 Gy (<i>n</i> = 50) TBI in combination with fludarabine and PTCy. Median patient age in the 8 Gy TBI cohort was 63 (37–79) and 37 (18–56) in the 12 Gy TBI cohort and median follow-up time was 21 months (range 1–92).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>OS and LFS at 2 years after 8 Gy were 65% and 55% versus 74% and 74% after 12 Gy (<i>p</i> = 0.3 and <i>p</i> = 0.2, respectively). CIR and NRM at 2 years were 27% and 14% after 8 Gy versus 4% and 20% after 12 Gy (<i>p</i> = 0.004 and <i>p</i> = 0.4, respectively). MRD-positive (+) patients (<i>n</i> = 26) receiving 12 Gy (<i>n</i> = 19) showed better OS (<i>p</i> = 0.01), LFS (<i>p</i> = 0.009), GRFS, lower CIR (<i>p</i> = 0.02), and similar NRM than did MRD+ patients receiving 8 Gy (<i>n</i> = 7). MRD-negative (−) patients (<i>n</i> = 38) receiving 12 Gy (<i>n</i> = 27) had similar OS, LFS, GRFS, lower CIR, and higher NRM (<i>p</i> = 0.04) than did MRD− patients receiving 8 Gy (<i>n</i> = 11).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study demonstrates that 8 Gy TBI in comparison to 12 Gy TBI results in low NRM but a high relapse rate with similar OS, LFS, and GRFS. In MRD+ high-risk ALL patients, allogeneic SCT with 12 Gy TBI leads to improved OS, LFS, GRFS, and a low relapse rate. Prospective studies comparing the different treatment regimens with larger MRD patient cohorts are needed to confirm this data.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"79-88"},"PeriodicalIF":2.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Frontline Single-Agent Rituximab in Extranodal Marginal Zone Lymphoma","authors":"Camilla Mazzoni,&nbsp;Lisa Argnani,&nbsp;Beatrice Casadei,&nbsp;Alessandro Broccoli,&nbsp;Giulia Gabrielli,&nbsp;Nicole Fabbri,&nbsp;Gabriele Gugliotta,&nbsp;Cinzia Pellegrini,&nbsp;Matteo Carella,&nbsp;Gianmarco Bagnato,&nbsp;Marianna Gentilini,&nbsp;Alice Morigi,&nbsp;Pierluca Maglio,&nbsp;Martina Cantelli,&nbsp;Vittorio Stefoni,&nbsp;Pier Luigi Zinzani","doi":"10.1111/ejh.14306","DOIUrl":"10.1111/ejh.14306","url":null,"abstract":"<p>First-line therapy for patients with extranodal marginal zone lymphoma (EMZL) is not well established, except for eradication therapy for <i>Helicobacter pylori</i> in early gastric MZL. Various regimens, for example, locoregional treatment and systemic chemo-immunotherapy, can be used depending on the site and stage of disease. Single-agent rituximab is a useful approach in the setting of localized, low-intermediate risk EMZL. The aim our research was to analyze the effectiveness and safety of single-agent rituximab (375 mg/m² once weekly for 4 weeks) in naïve EMZL in a real-life setting. The primary endpoint was the overall response rate (ORR), secondary endpoints were progression-free (PFS), overall (OS) and disease-free survivals (DFS), and drug tolerability. Fifty-nine patients were analyzed. Median time between diagnosis and rituximab was 3.6 months. The ORR was 89.9%, with 67.8% complete response (CR). Median DFS and PFS were reached at 6.3 and 5.3 years, respectively. After a median follow-up of 5 years, median OS was not reached. The most common adverse event was infusion reaction, reported in 28 cases, mainly during the first infusion and easily manageable. Single-agent rituximab may represent a valid therapeutic option in the first-line treatment of EMZL, at least for localized disease, with a favorable toxicity profile.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"70-78"},"PeriodicalIF":2.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Musculoskeletal Symptoms and Misdiagnoses in Children With Acute Myeloid Leukaemia: A Nationwide Cohort Study","authors":"Anne Birthe Helweg Jensen,&nbsp;Helene Riis Pontoppidan Andersen,&nbsp;Sarah Thorius Jensen,&nbsp;Christina Friis Jensen,&nbsp;Jesper Amstrup,&nbsp;René Mathiasen,&nbsp;Kasper Amund Henriksen,&nbsp;Henrik Hasle,&nbsp;Michael Thude Callesen,&nbsp;Ninna Brix","doi":"10.1111/ejh.14303","DOIUrl":"10.1111/ejh.14303","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Childhood cancer often presents with non-specific signs and symptoms that might mimic non-malignant disorders including musculoskeletal diseases, potentially leading to rheumatic and orthopaedic misdiagnoses. We aimed to compare clinical presentation, diagnostic interval and survival in paediatric acute myeloid leukaemia (AML) with and without initial musculoskeletal symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This nationwide retrospective, cohort study reviewed medical records of 144 children below 15 years diagnosed with AML in Denmark from 1996 to 2018.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Musculoskeletal symptoms occurred in 29% (42/144) of children with AML and 8% (11/144) received an initial musculoskeletal misdiagnosis, being mainly non-specific and pain-related. The children with and without musculoskeletal symptoms did not differ markedly up to the diagnosis of AML and blood counts were affected equally in both groups. However, the children with prior musculoskeletal symptoms were more likely to have elevated levels of LDH and ferritin. Furthermore, they revealed a tendency towards a longer total interval (median 53 days vs. 32 days, <i>p</i> = 0.07), but the overall survival did not differ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AML should be considered as an underlying cause in children with unexplained musculoskeletal symptoms and abnormal blood counts. Concomitant elevation of LDH and ferritin should strengthen the suspicion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"57-69"},"PeriodicalIF":2.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloproliferative Neoplasms and Dementia Risk: A Population-Based Cohort Study","authors":"Yuelian Sun,&nbsp;Katalin Veres,&nbsp;Hans Carl Hasselbalch,&nbsp;Henrik Frederiksen,&nbsp;Lene Sofie Granfeldt Østgård,&nbsp;Erzsébet Horváth-Puhó,&nbsp;Victor W. Henderson,&nbsp;Henrik Toft Sørensen","doi":"10.1111/ejh.14297","DOIUrl":"10.1111/ejh.14297","url":null,"abstract":"&lt;p&gt;Dementia is a severely disabling condition that affected 50 million people and is likely to triple by 2050, thus placing a heavy burden on families and society [&lt;span&gt;1&lt;/span&gt;]. Several dementia risk factors have been identified, including age, sex, and environmental and lifestyle factors together with genetic factors [&lt;span&gt;2, 3&lt;/span&gt;]. Many of the known risk factors, such as obesity, diabetes, hypertension, and smoking, are potentially modifiable [&lt;span&gt;2, 3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Chronic inflammation is a potential key pathogenic factor in the development of dementia [&lt;span&gt;4, 5&lt;/span&gt;], but many of its aspects and clinical implications are poorly understood. Philadelphia chromosome–negative chronic myeloproliferative neoplasms (MPNs) are chronic blood cancers caused by the somatic driver mutations &lt;i&gt;JAK2V617F&lt;/i&gt;, &lt;i&gt;CALR&lt;/i&gt;, and &lt;i&gt;MPL&lt;/i&gt; in hematopoietic stem cells [&lt;span&gt;6&lt;/span&gt;]. These specific gene mutations contribute to the inflammatory and thrombogenic state in patients diagnosed with MPNs, and the prediagnostic phase of MPNs may span as many as 15–20 years [&lt;span&gt;7&lt;/span&gt;]. MPNs have been proposed as a human neuroinflammation model for studying the development of dementia [&lt;span&gt;8&lt;/span&gt;]. To our knowledge, no population-based studies have examined associations between MPNs and dementia risk.&lt;/p&gt;&lt;p&gt;We conducted a cohort study to examine these associations in comparison with a general population comparison cohort. The study also used chronic lymphocytic leukemia (CLL) and chronic myelogenous leukemia (CML) as control diseases. CLL has a long clinical course, like MPNs, but chronic inflammation is not considered a driving force for CLL development and disease progression [&lt;span&gt;9&lt;/span&gt;]. CML is another chronic myeloproliferative blood cancer caused by a specific reciprocal chromosome translocation (Philadelphia chromosome) and does not involve a chronic inflammatory state to the same extent as Philadelphia chromosome–negative MPNs [&lt;span&gt;10&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We identified 9895 patients with MPNs, 9465 patients with CLL, and 1530 patients with CML (Figure S1a–c). The patients with MPNs included 3090 with ET, 3910 with PV, 410 with MF, and 2520 with unspecified MPN. Table 1 shows the baseline characteristics and follow-up information for the MPN, CLL, and CML cohorts. Patients with MPNs had more chronic inflammatory comorbidities than did their matched general population comparators, whereas patients with CLL did not (Table 1, Figure S2). Patients with CML were more likely to have comorbidities than were their comparison cohort comparators, but this difference was less pronounced than that observed in the MPN cohort (Table 1, Figure S2).&lt;/p&gt;&lt;p&gt;During the follow-up (median of 5 years for the MPN cohort and 7 years for the general population cohort), 520 (5.3%) people in the MPN cohort and 7070 (7.4%) people in the general population cohort were diagnosed with dementia, and 50.0% (&lt;i&gt;n&lt;/i&gt; = 4945) of the MPN cohort and 31.4% (&lt;i&gt;n&lt;/i&gt; = 30 1","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"45-56"},"PeriodicalIF":2.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Choice of Frontline Tyrosine-Kinase Inhibitor and Early Events in Very Elderly Patients With Chronic Myeloid Leukemia in Chronic Phase: A “Campus CML” Study","authors":"C. Bucelli,&nbsp;I. Capodanno,&nbsp;M. C. Miggiano,&nbsp;F. Cavazzini,&nbsp;S. Leonetti Crescenzi,&nbsp;S. Russo,&nbsp;I. Carmosino,&nbsp;M. Annunziata,&nbsp;F. Sorà,&nbsp;M. Bonifacio,&nbsp;L. Luciano,&nbsp;G. Caocci,&nbsp;G. Loglisci,&nbsp;C. Elena,&nbsp;F. Lunghi,&nbsp;R. Mullai,&nbsp;I. Attolico,&nbsp;G. Binotto,&nbsp;E. Crisà,&nbsp;P. Sportoletti,&nbsp;A. Di Veroli,&nbsp;A. R. Scortechini,&nbsp;A. P. Leporace,&nbsp;A. Maggi,&nbsp;M. Crugnola,&nbsp;F. Stagno,&nbsp;R. Sancetta,&nbsp;P. Murgano,&nbsp;D. Rapezzi,&nbsp;D. Luzi,&nbsp;D. I. Vincelli,&nbsp;S. Galimberti,&nbsp;M. Bocchia,&nbsp;C. Fava,&nbsp;A. Malato,&nbsp;E. Abruzzese,&nbsp;G. Saglio,&nbsp;G. Specchia,&nbsp;M. Breccia,&nbsp;A. Iurlo,&nbsp;M. Tiribelli,&nbsp;R. Latagliata","doi":"10.1111/ejh.14299","DOIUrl":"10.1111/ejh.14299","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The study aimed to evaluate the utilization of frontline TKI therapy in a large cohort of elderly CP-CML patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis was conducted on 332 CP-CML patients aged 75 years or older among 1929 diagnosed from January 2012 to December 2019 followed at 36 participating Hematology Centers involved in the “Campus CML” project.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the patients analyzed, 85.8% received imatinib (IM) while 14.2% received second-generation TKIs (2G-TKI), 59.5% dasatinib, and 40.5% nilotinib. Most patients initiated IM at standard dose (67.3%) while 32.7% at reduced dose. A similar trend was observed with 2G-TKIs. The cumulative incidence of permanent TKI discontinuation at 12 months was 28.4%, primarily due to primary resistance (10.1%) and extra-hematologic toxicity (9.5%), with no significant difference between IM and 2G-TKI groups. Following the introduction of generic IM in Italy in 2018, IM usage increased significantly compared with 2G-TKIs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IM was in our Centers the preferred frontline therapy for older CP-CML patients, with increasing utilization after the introduction of generic formulations. However, 2G-TKIs are still used in a substantial proportion of patients, suggesting individualized physician assessments regarding patient suitability and expectations. Further investigation is needed to assess efficacy and safety of reduced TKI doses in this patient population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"37-44"},"PeriodicalIF":2.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Real-World Data-Based Analysis of Prognostic Indices as Part of Trial Eligibility Criteria in Diffuse Large B-Cell Lymphoma Patients","authors":"Jelena Jelicic,&nbsp;Karen Juul-Jensen,&nbsp;Zoran Bukumiric,&nbsp;Mikkel Runason Simonsen,&nbsp;Michael Roost Clausen,&nbsp;Ahmed Ludvigsen Al-Mashhadi,&nbsp;Robert Schou Pedersen,&nbsp;Christian Bjørn Poulsen,&nbsp;Anne Ortved Gang,&nbsp;Peter Brown,&nbsp;Tarec Christoffer El-Galaly,&nbsp;Thomas Stauffer Larsen","doi":"10.1111/ejh.14301","DOIUrl":"10.1111/ejh.14301","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Recent front-line clinical trials used the International Prognostic Index (IPI) to identify trial-eligible patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, many IPI-like variants with improved accuracy have been developed over the years for rituximab-treated patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed the impact of International Prognostic Indices on patient enrolment in clinical trials, aiming to exclude low-risk IPI patients based on POLARIX/EPCORE DLBCL-2 trial criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 2877 patients in the Danish Lymphoma Registry who would have been eligible for the POLARIX trial if patients with IPI 0–1 scores were included. IPI and NCCN-IPI assigned 33.3% and 11.9% of patients to the low-risk group, respectively. Shorter 5-year overall survival (91.4% vs. 97.5%), higher relapse rate (9.9% vs. 4.4%), and more deaths (16.1% vs. 4.4%) occurred in the low-risk IPI group compared with low-risk NCCN-IPI group. Analyzed models failed to identify true high-risk patients with poor prognosis. Similar results were found in the confirmatory cohort developed based on EPCORE DLBCL-2 trial eligibility criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>True low-risk patients are more optimal identified by NCCN-IPI and should be excluded from front-line clinical trials due to their excellent prognosis. However, additional high-risk factors besides clinical prognostic models need to be considered when selecting trial-eligible patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"26-36"},"PeriodicalIF":2.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venetoclax Combined With FLAG-IDA in Refractory or Relapsed Acute Myeloid Leukemia","authors":"Kai Wille,&nbsp;Marvin Dumke,&nbsp;Nadine Wilsdorf,&nbsp;Parvis Sadjadian,&nbsp;Artur Schneider,&nbsp;Stephanie Jender-Bartling,&nbsp;Vera Kolatzki,&nbsp;Anette Horstmann,&nbsp;Raphael Meixner,&nbsp;Marina Jiménez-Muñoz,&nbsp;Christiane Fuchs,&nbsp;Hans-Joachim Tischler,&nbsp;Martin Griesshammer","doi":"10.1111/ejh.14302","DOIUrl":"10.1111/ejh.14302","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The prognosis of patients with refractory or relapsed AML (R/R-AML) is very limited. To (re)achieve complete remission, there has recently been increasing evidence that the combination of venetoclax (VEN) with chemotherapy is associated with improved outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>Our retrospective, single-center study of 53 R/R-AML patients with a median follow-up time of 11.0 months compared standard salvage chemotherapy (FLAG-Ida or HAM in <i>n</i> = 35 patients) with a combination of venetoclax (VEN) and FLAG-Ida (FLAVIDA in <i>n</i> = 18 patients) concerning safety and efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Regarding the primary endpoints, there was a statistically significant increased event free survival (EFS) in the FLAVIDA group compared to patients with standard chemotherapy based on the univariate log-rank-test and in the multivariate Cox regression analysis (HR 0.22 [95% CI 0.05, 0.97]). There were no differences between the two groups in terms of patients developing febrile neutropenia CTCAE III° and IV° or a delay in hematological recovery. In addition, a clear trend towards an improved overall response rate (78% vs. 51%) was demonstrated in the FLAVIDA group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The FLAVIDA regimen represents a promising treatment alternative for R/R AML patients with a high response rate and significantly improved EFS compared to standard chemotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 1","pages":"17-25"},"PeriodicalIF":2.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Strategy for Adult T-Cell Leukemia Treatment Targeting Glycogen Synthase Kinase-3β","authors":"Chie Ishikawa,&nbsp;Naoki Mori","doi":"10.1111/ejh.14300","DOIUrl":"10.1111/ejh.14300","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The role of glycogen synthase kinase (GSK)-3β in adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type 1 (HTLV-1) is paradoxical and enigmatic. Here, we investigated the role of GSK-3β and its potential as a therapeutic target for ATL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cell proliferation/survival, cell cycle, apoptosis, and reactive oxygen species (ROS) generation were examined using the WST-8 assay, flow cytometry, and Hoechst 33342 staining, respectively. Expression of GSK-3β and cell cycle/death-related proteins, and survival signals was analyzed using RT-PCR, immunofluorescence staining, and immunoblotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HTLV-1-infected T-cell lines showed nuclear accumulation of GSK-3β. GSK-3β knockdown and its inhibition with 9-ING-41 and LY2090314 suppressed cell proliferation/survival. 9-ING-41 induced G2/M arrest by enhancing the expression of γH2AX, p53, p21, and p27, and suppressing the expression of CDK1, cyclin A/B, and c-Myc. It induced caspase-mediated apoptosis by decreasing the expression of Bcl-xL, Mcl-1, XIAP, c-IAP1/2, and survivin, and increasing the expression of Bak and Bax. 9-ING-41 also induced ferroptosis and necroptosis, promoted JNK phosphorylation, and suppressed IKKγ and JunB expression. It inhibited the phosphorylation of IκBα, Akt, and STAT3/5, induced ROS production, and reduced glycolysis-derived lactate levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GSK-3β functions as an oncogene in ATL and could be a potential therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 6","pages":"852-862"},"PeriodicalIF":2.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perinatal Outcomes Following Intravenous Iron for Treatment of Iron Deficiency With and Without Anemia","authors":"Kimberly S. Ryan,&nbsp;Kylee L. Martens,&nbsp;Bharti Garg,&nbsp;Boris I. Chobrutskiy,&nbsp;Madeline A. Hedges,&nbsp;Olivia L. Hagen,&nbsp;Jean M. G. Sabile,&nbsp;Adam K. Lewkowitz,&nbsp;Methodius G. Tuuli,&nbsp;Thomas G. Deloughery,&nbsp;Joseph J. Shatzel,&nbsp;Jamie O. Lo,&nbsp;Ashley E. Benson","doi":"10.1111/ejh.14298","DOIUrl":"10.1111/ejh.14298","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine maternal and neonatal outcomes in individuals with iron deficiency receiving antepartum intravenous (IV) iron supplementation, stratified by the degree of anemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Study Design</h3>\u0000 \u0000 <p>Retrospective cohort study of iron-deficient pregnant patients who received at least one IV infusion of iron (iron sucrose, low molecular weight iron dextran [LMWID], or ferric carboxymaltose) during their pregnancy from January 1, 2011 through June 16, 2022. Our primary outcomes included both neonatal composite morbidity and maternal composite morbidity in the context of maternal anemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients who received LMWID had fewer infusion visits, received higher total doses of iron and had a more substantial correction of hemoglobin compared to those who received iron sucrose (<i>p</i> &lt; 0.01). Maternal anemia at the time of admission was not associated with neonatal composite morbidity. However, there was a significant association between anemia status and maternal composite outcome (<i>p</i> = 0.05). Anemia at time of delivery was associated with the likelihood of requiring a blood transfusion (<i>p</i> = 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study reinforces previous findings emphasizing the adverse effects of iron deficiency on maternal health and the role of IV iron in reducing these risks.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 6","pages":"842-851"},"PeriodicalIF":2.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}