European Journal of Haematology最新文献

{"title":"Favourable Outcome of Relapsed PCNSL Among Transplant Eligble Patients","authors":"Eetu Pellonperä,&nbsp;Inka Puhakka,&nbsp;Hanne Kuitunen,&nbsp;Aino Rönkä,&nbsp;Kaisa Sunela,&nbsp;Milla E. L. Kuusisto,&nbsp;Tuula Klaavuniemi,&nbsp;Pekka Jäkälä,&nbsp;Aino Rajamäki,&nbsp;Ulla-Mari Arkko,&nbsp;Outi Kuittinen","doi":"10.1111/ejh.14382","DOIUrl":"10.1111/ejh.14382","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The prognosis of relapsed primary central nervous system lymphoma remains a concern. This study aimed to compare the effects of various patient- and disease-related factors on the prognosis of relapsed primary central nervous system lymphoma (PCNSL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively collected real-world data from eight Finnish hospitals on 198 patients diagnosed with PCNSL between 2003 and 2020. Characteristics of the patients were available. At total of 63 patients with relapses were included after excluding seven isolated ocular relapses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median progression-free survival after relapse was 3 months. The median overall survival after the first relapse (OS2) was 4 months. Patients aged 70 or younger with good performance status who received autologous stem cell transplantation (ASCT) consolidation as second-line treatment had significantly better OS2 of 39 months (<i>p</i> = 0.002). OS2 for patients without ASCT consolidation remained at 3 months. Age over 70 years, poor performance status, and a first-line progression-free survival of less than 6 months negatively impacted the prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study confirms previous findings of poor outcomes in patients with relapsed PCNSL. Some subgroups, particularly those receiving ASCT consolidation, can achieve long-term remission with current treatment options. New treatment strategies are needed for patients ineligible for ASCT or those who do not respond to salvage induction therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 5","pages":"840-846"},"PeriodicalIF":2.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946884","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":"Impact of Trial Eligibility Criteria on Outcomes of 1183 Patients With Follicular Lymphoma Treated in the Real-World Setting","authors":"Tine Litske Bennedsen,&nbsp;Mikkel Runason Simonsen,&nbsp;Paw Jensen,&nbsp;Peter Brown,&nbsp;Pär Josefsson,&nbsp;Arushi Khurana,&nbsp;Matthew Maurer,&nbsp;Michael Roost Clausen,&nbsp;Andriette Dessau-Arp,&nbsp;Jennifer Bøgh Jørgensen,&nbsp;Judit Jørgensen,&nbsp;Thomas Stauffer Larsen,&nbsp;Lars Møller Pedersen,&nbsp;Lasse Hjort Jakobsen,&nbsp;Tarec Christoffer El-Galaly","doi":"10.1111/ejh.14373","DOIUrl":"10.1111/ejh.14373","url":null,"abstract":"<div>\u0000 \u0000 <p>The development of new first-line treatments for patients with follicular lymphoma (FL) is becoming increasingly challenging due to already excellent survival outcomes. The present study investigated the outcomes of patients with FL who underwent contemporary first-line therapies but would not have been eligible for inclusion in recent trials and explored how commonly used in/exclusion criteria impacted their survival outcomes. This study included adult patients diagnosed with FL in the period 2000–2018 registered in the Danish Lymphoma Registry. Through searches on ClinicalTrials.gov, four recent 1st line phase 3 randomized controlled trials with R-Bendamustine, R-CVP, and/or R-CHOP as control or experimental arms were included. Inclusion and exclusion criteria for each trial were retrieved and categorized. Patients were then divided into trial-eligible and ineligible groups according to blood test results correlated to organ function and ECOG performance score (PS). Survival outcomes were significantly worse among trial-ineligible patients, with adjusted differences between trial-eligible and ineligible patients of 12%–20% in five-year overall survival (OS) overall. Inclusion criteria based on PS and renal function were the main drivers of OS differences. More inclusive trials will lead to faster recruitment and secure focus on developing medicines for the group of patients with the worst outcomes.</p>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 5","pages":"832-839"},"PeriodicalIF":2.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946897","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":"The Role of Lifestyle and Environmental Factors in the Pathogenesis of Multiple Myeloma","authors":"Anna Suska,&nbsp;Agata Tyczyńska,&nbsp;Jan Maciej Zaucha,&nbsp;Anna Kopińska,&nbsp;Grzegorz Helbig,&nbsp;Mirosław Markiewicz,&nbsp;Katarzyna Warzybok,&nbsp;Ewa Leder,&nbsp;Sebastian Grosicki,&nbsp;Bogusław Machaliński,&nbsp;Bartłomiej Baumert,&nbsp;Michał Bator,&nbsp;Lidia Usnarska-Zubkiewicz,&nbsp;Szymon Fornagiel,&nbsp;Hanna Ciepłuch,&nbsp;Anna Waszczuk-Gajda,&nbsp;Kamila Kruczkowska-Tarantowicz,&nbsp;Piotr Rzepecki,&nbsp;Marek Hus,&nbsp;Anna Morawska-Krekora,&nbsp;Małgorzata Raźny,&nbsp;Grzegorz Charliński,&nbsp;Anna Puła,&nbsp;Ewa Nita,&nbsp;Małgorzata Wojciechowska,&nbsp;Małgorzata Krawczyk-Kuliś,&nbsp;Joanna Goldberg,&nbsp;Tomasz Woźny,&nbsp;Marek Rodzaj,&nbsp;Dariusz Olejarz,&nbsp;Marlena Gronau-Dziurkowska,&nbsp;Ewa Skalniak,&nbsp;Janusz Krzysztoń,&nbsp;Karolina Niezabitowska,&nbsp;Artur Jurczyszyn","doi":"10.1111/ejh.14356","DOIUrl":"10.1111/ejh.14356","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The study evaluated the impact of lifestyle and environmental exposure on the etiology of multiple myeloma (MM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A multicenter case–control study was conducted in 20 hematology centers and in 5 outpatient clinics in Poland. The questionnaire on exposure to potential risk factors including sociodemographic data, lifestyle, and environmental factors was completed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 274 patients with newly diagnosed MM and 208 patients from primary healthcare centers in the control group were enrolled in the study. Regarding lifestyle, sports practiced systematically for at least half a year play a protective role in the development of myeloma (OR = 0.40, 95% CI, 0.28–0.58, <i>p</i> &lt; 0.001). Among environmental factors harmful exposures that increase the likelihood of the development of MM include pesticides (OR = 3.29, <i>p</i> &lt; 0.001), asphalt (OR = 2.42, <i>p</i> = 0.026), coal dust (OR = 2.27, <i>p</i> = 0.004), organic vapors (OR = 2.11, <i>p</i> = 0.001), metal dust (OR = 2.07, <i>p</i> = 0.023), exhaust fumes (OR = 2.03, <i>p</i> &lt; 0.01), and chemicals (OR = 1.80, <i>p</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The pathogenesis of MM is complex with the impact of modifiable factors. Lifestyle, with physical activity, seems to play a key role.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 5","pages":"812-821"},"PeriodicalIF":2.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946922","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":"Pomalidomide, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Final Survival and Subgroup Analyses From the OPTIMISMM Trial","authors":"Paul Richardson,&nbsp;Meral Beksaç,&nbsp;Albert Oriol,&nbsp;Jindriska Lindsay,&nbsp;Fredrik Schjesvold,&nbsp;Monica Galli,&nbsp;Münci Yağcı,&nbsp;Alessandra Larocca,&nbsp;Katja Weisel,&nbsp;Xin Yu,&nbsp;Cynthia Donahue,&nbsp;Jorge Acosta,&nbsp;Teresa Peluso,&nbsp;Meletios Dimopoulos","doi":"10.1111/ejh.14365","DOIUrl":"10.1111/ejh.14365","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>In the OPTIMISMM trial, pomalidomide/bortezomib/dexamethasone (PVd) significantly prolonged median progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) in lenalidomide-exposed relapsed and refractory multiple myeloma (RRMM). We report final overall survival (OS) and updated efficacy analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adults with RRMM who had 1–3 prior regimens, including lenalidomide (≥ 2 cycles), were assigned (1:1) to PVd or Vd. Primary endpoint: PFS. Prespecified secondary endpoint: OS. Prespecified exploratory endpoints: PFS2 and subgroup efficacy analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>With an overall event rate of 70.0%, OS data were mature in the intent-to-treat population (<i>N</i> = 559). After median follow-up of 64.5 months (data cutoff: May 13, 2022), median OS was 35.6 months with PVd versus 31.6 months with Vd (HR 0.94, 95% CI 0.77–1.15, <i>p</i> = 0.571); adjusting for subsequent therapies, OS improved with PVd versus Vd (HR 0.76, 95% CI 0.619–0.931, <i>p</i> = 0.008). Median PFS2 was 22.1 versus 16.9 months, respectively (HR 0.77, 95% CI 0.64–0.94, nominal <i>p</i> = 0.008). Treatment-emergent adverse events led to study drug discontinuation in 92 (33.1%) and 53 (19.6%) patients in PVd and Vd arm, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Findings showed a nonsignificant trend towards improved OS with PVd versus Vd. PFS2 favored PVd, supporting its use in RRMM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 5","pages":"822-831"},"PeriodicalIF":2.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946904","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":"Electrophysiological Studies in Combination With Interim-Positron Emission Tomography Scan for Prevention of Severe Brentuximab-Vedotin-Induced Neurotoxicity","authors":"Luca Pezzullo,&nbsp;Giuseppe Piscosquito,&nbsp;Lorenzo Settembre,&nbsp;Stefano Avventura,&nbsp;Bianca Serio,&nbsp;Giuseppe De Biasi,&nbsp;Michela Rizzo,&nbsp;Ciro Maria Noioso,&nbsp;Matteo D'Addona,&nbsp;Annamaria Landolfi,&nbsp;Claudia Vinciguerra,&nbsp;Valentina Giudice,&nbsp;Paolo Barone,&nbsp;Carmine Selleri","doi":"10.1111/ejh.14384","DOIUrl":"10.1111/ejh.14384","url":null,"abstract":"<p>Brentuximab-vedotin (BV)-induced neurotoxicity (BVIN), a frequent adverse event caused by this monoclonal antibody, is the primary reason for dose modification or drug discontinuation, and is characterized by sensory, motor, and/or autonomic peripheral nerve dysfunctions. Although reversible, BVIN can persist for months or years after treatment and negatively affect quality of life (QoL). Currently, BVIN is managed by dose adjustment or drug interruption, leading to an increased risk of disease relapse. Therefore, early recognition and appropriate management are essential to improve clinical outcomes. In this real-life study, we identified predictive factors for moderate/severe BVIN to reduce the risk of irreversible neuropathy. A total of 22 patients treated with BV were enrolled and BVIN was monitored by electro-neurography and neurological examinations every 2 cycles of therapy, while QoL by clinical questionnaires. We showed that recovery rate from moderate/severe BVIN was low, and sensory nerves were the most affected, negatively impacting QoL. BV dose reduction based on interim PET re-evaluation in patients with hematological response resulted in a significant reduction of BVIN onset with high long-term QoL. Therefore, electrophysiological tests could be useful tools to prevent moderate/severe BVIN onset, and their combination with interim PET imaging could allow dosage adjustments thus simultaneously minimizing risks of disease relapse and BVIN development. However, further studies on larger prospective randomized cohorts are needed to confirm our preliminary results.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 5","pages":"802-811"},"PeriodicalIF":2.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946879","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":"Hyper-CVAD and Modified CALGB-10403 Regimens in Adult Patients With Philadelphia-Negative Acute Lymphoblastic Leukemia: A Comparative Study","authors":"Jessica Zalapa-Soto,&nbsp;Fausto Alfredo Rios-Olais,&nbsp;Lyam Carlo Chacón-Rangel,&nbsp;Analy Mora-Cañas,&nbsp;Mario Meza-Meza,&nbsp;Juan Rangel-Patiño,&nbsp;Roberta Demichelis-Gómez","doi":"10.1111/ejh.14381","DOIUrl":"10.1111/ejh.14381","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Acute lymphoblastic leukemia (ALL) has a higher incidence in Latin America, with adult patients experiencing worse long-term outcomes despite high complete remission (CR) rates. When treated with adult regimens, 3-year overall survival (OS) is approximately 20%. However, adopting pediatric-inspired regimens (PIRs) has shown improved outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a comparative analysis of Hispanic adult patients with newly diagnosed Ph-negative ALL, treated with either a PIR, a modified CALGB 10403 (mCALGB), or the adult regimen Hyper-CVAD between January 2015 and May 2023. The primary endpoint was OS and among secondary endpoints relapse-free survival (RFS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 100 patients, 35 were treated with Hyper-CVAD and 65 with mCALGB. Median age was 26 years (range, 20.2–38). The median OS was 54.2 months (95% CI 28.3–80.1), with a non-reached median OS in the mCALGB group (95% CI NR-NR) versus 22.4 months (95% CI 13.7–31) for Hyper-CVAD. The 3-year OS was 64.9% versus 34.9%, <i>p</i> = 0.034. Treatment with mCALGB was independently associated with OS (HR 0.29, 95% CI 0.13–0.66, <i>p</i> = 0.003) and RFS (HR 0.29, 95% CI 0.14–0.59, <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Treatment with mCALGB was independently associated with benefits regarding RFS and OS when compared to Hyper-CVAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 5","pages":"793-801"},"PeriodicalIF":2.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946892","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":"Outcomes of Elderly Patients Admitted to the Intensive Care Unit for Newly Diagnosed Acute Myeloid Leukemia","authors":"Guillaume Berton,&nbsp;Marie-Anne Hospital,&nbsp;Sylvain Garciaz,&nbsp;Camille Rouzaud,&nbsp;Valerio Maisano,&nbsp;Yosr Hicheri,&nbsp;Evelyne D'Incan Corda,&nbsp;Jerome Rey,&nbsp;Magali Bisbal,&nbsp;Antoine Sannini,&nbsp;Laurent Chow Chine,&nbsp;Luca Servan,&nbsp;Frederic Gonzalez,&nbsp;Norbert Vey,&nbsp;Djamel Mokart,&nbsp;Colombe Saillard","doi":"10.1111/ejh.14366","DOIUrl":"https://doi.org/10.1111/ejh.14366","url":null,"abstract":"<p>Acute myeloid leukemias (AMLs) are the hematological malignancies with the highest need for intensive care unit (ICU) admission due to their association with various life-threatening situations. Limited data exist regarding the outcomes of elderly individuals with AML admitted to the ICU. However, current therapeutic protocols offer the potential for extended survival in this population. This retrospective, monocentric study focused on the outcomes of individuals aged ≥ 60 years admitted to the ICU for newly diagnosed AML. It included 139 patients admitted to the ICU at the Paoli-Calmettes Institute between April 2010 and October 2020, during the initial phase of AML management. Patients were categorized into three groups based on the presence of biological criteria indicating “high risk” for complications (thrombocytopenia &lt; 50 000/mm³ and leukocytosis &gt; 50 000/mm³) and organ failure. Multiple logistic regression models were employed to identify predictive factors for in-hospital and day 90 mortality, while Cox regression was used for 1-year mortality. The rates of in-hospital, day 90, and 1-year mortality were 37%, 42%, and 60%, respectively. Variables associated with in-hospital mortality included the Charlson Comorbidity Index, the need for invasive mechanical ventilation (MV), and multi-organ failure. ELN17 risk was significantly associated with 1-year mortality rates. This study demonstrates the benefits of ICU management for individuals aged ≥ 60 years during the initial phase of AML. It illustrates the effects of age, comorbidities, and the severity of organ failures on short-term mortality and highlights the impact of classical prognostic markers on long-term mortality.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 4","pages":"679-689"},"PeriodicalIF":2.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14366","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554560","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":"SARS-COV-2 Pre-Exposure Prophylaxis With Tixagevimab-Cilgavimab in Haematological, Immunocompromised Patients in the Omicron Era","authors":"Manuela A. Hoechstetter,&nbsp;Eva-Maria Hollwich,&nbsp;Doris Illner,&nbsp;Thu-Trang Pham,&nbsp;Michael von Bergwelt-Baildon,&nbsp;Martin Dreyling,&nbsp;Clemens-Martin Wendtner","doi":"10.1111/ejh.14377","DOIUrl":"10.1111/ejh.14377","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pre-exposure prophylaxis with tixagevimab-cilgavimab significantly reduced severe COVID-19 outcomes in high-risk individuals during the pre-Omicron era (PROVENT trial). However, efficacy in patients with haematological malignancies (HM) was underreported. The rapid emergence of Omicron strains in 2021 showed reduced neutralizing activity in preclinical data, but real-world data remains limited due to short follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>We aimed to evaluate the effectiveness and safety of tixagevimab-cilgavimab in 86 HM patients during the early Omicron wave, including the BA.2, BA.5, and XBB.1 sublineages.</p>\u0000 \u0000 <p>These patients received PrEP between February and August 2022 due to impaired vaccine response (72%) and B-cell depletion (46.5%). They were followed prospectively until April 2023, with a median follow-up of 297 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Breakthrough SARS-CoV-2 infections occurred in 32.6% of patients, with 22.1% within six months. Infections within six months were milder and shorter. B-cell depletion within six (<i>p</i> = 0.035) and twelve months (<i>p</i> = 0.016) was identified as risk factor for breakthrough infections. No new safety events were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data showed that tixagevimab-cilgavimab prophylaxis effectively reduces severe COVID-19 outcomes in patients with HM, particularly within the first six months, even during the Omicron era. However, those with recent B-cell depletion (within 12 months) remained at high risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 4","pages":"690-699"},"PeriodicalIF":2.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930910","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":"Impact of Day 11 Methotrexate Dose Adjustments due to Mucositis on the Outcomes Following Allogeneic Stem Cell Transplant in the Setting of Anti Thymocyte Globulin (ATG) Based GVHD Prophylaxis","authors":"Vinita Dhir,&nbsp;Connor Prince,&nbsp;David Allan,&nbsp;Harold Atkins,&nbsp;Christopher Bredeson,&nbsp;Natasha Kekre,&nbsp;Michael Kennah,&nbsp;Ashish Masurekar,&nbsp;Ram Vasudevan Nampoothiri","doi":"10.1111/ejh.14380","DOIUrl":"10.1111/ejh.14380","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dose adjustments of Day 11 Methotrexate (MTx) for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation (HCT) are common due to mucositis, renal injury, or other reasons. The impact of omitting or adjusting doses of MTx in the era of ATG-based GVHD prophylaxis remains unexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed the outcomes of all adult patients undergoing allogeneic HCT who received ATG-based GVHD prophylaxis at The Ottawa Hospital from January 2019 to December 2022. We compared outcomes of patients having only Day 11 MTx dose reductions due to mucositis(MTxRD group) with patients receiving full dose MTx on all 4 days (MTxFD group). The impact of Day 11 MTx dose reduction on outcomes were assessed using Kaplan–Meier analyses and log rank test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three hundred and four patients (median age 58 [17–74] years; 64% male) underwent allogeneic HCT during the study period. Baseline characteristics were similar between the MTxRD group (<i>n</i> = 69) and MTxFD group (<i>n</i> = 199) except for an increased proportion of MAC regimens in MTxRD group. The incidence of severe aGVHD (7.2% vs. 7.5%; <i>p</i> = 0.96) and chronic GVHD (15.9% vs. 15.6%; <i>p</i> = 0.89) were not different between the two groups. The 2-year OS (59% vs. 69.8%; <i>p</i> = 0.11), GRFS (42.4% vs. 47.6%; <i>p</i> = 0.32), NRM (17.7% vs. 12.2%; <i>p</i> = 0.45) or relapse/progression (CIR 27.4 vs. 26.6%; <i>p</i> = 0.55) were also similar between the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients receiving ATG-based GVHD prophylaxis regimens, there were similar GVHD and survival outcomes in patients who received no or reduced D11 MTx when compared to full dose MTx. Dose adjustments of D11 MTx due to mucositis appear to be safe in the era of ATG-based GVHD prophylaxis regimens.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 5","pages":"785-792"},"PeriodicalIF":2.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930906","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":"Advances and Challenges in Quizartinib-Based FLT3 Inhibition for Acute Myeloid Leukemia: Mechanisms of Resistance and Prospective Combination Therapies","authors":"Antonella Bruzzese,&nbsp;Enrica Antonia Martino,&nbsp;Caterina Labanca,&nbsp;Francesco Mendicino,&nbsp;Eugenio Lucia,&nbsp;Virginia Olivito,&nbsp;Teresa Rossi,&nbsp;Antonino Neri,&nbsp;Fortunato Morabito,&nbsp;Ernesto Vigna,&nbsp;Massimo Gentile","doi":"10.1111/ejh.14383","DOIUrl":"https://doi.org/10.1111/ejh.14383","url":null,"abstract":"<p>FLT3 mutations are among the most common genetic alterations in acute myeloid leukemia (AML) and are associated with poor prognosis. Significant advancements have been made in developing FLT3 inhibitors (FLT3Is), such as quizartinib, which have improved treatment outcomes in both newly diagnosed and relapsed/refractory AML. Resistance to FLT3Is remains a major clinical challenge, driven by diverse mechanisms including FLT3 point mutations, cellular escape pathways, and the influence of the bone marrow microenvironment. Sustained STAT5 phosphorylation, AXL upregulation, and CXCR4 signaling have been identified as key factors in FLT3I resistance. Additionally, metabolic adaptations have been shown to support the survival of FLT3I-resistant cells. Ongoing clinical trials are investigating various combination regimens, including quizartinib with chemotherapy, Bcl-2 inhibitors, hypomethylating agents, and immune-modulatory drugs, with promising preliminary results. The European LeukemiaNet 2022 guidelines recommend incorporating FLT3Is into treatment regimens; however, questions remain regarding the best timing for the administration of each FLT3I. Additional studies are required to determine the optimal FLT3I-based combinations, reduce resistance emergence, and improve outcomes. This review highlights the current state of FLT3I therapy, ongoing challenges with resistance, and future directions in optimizing treatment for FLT3-mutated AML, focusing on quizartinib.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 4","pages":"584-595"},"PeriodicalIF":2.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554561","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}