European Journal of Haematology最新文献

{"title":"TP53-Mutated Acute Myeloid Leukemia and Blast Phase Myeloproliferative Neoplasm: Distinct Mutation Leads to Poorer Prognosis.","authors":"Dong Chen, Miguel Cantu, Alexa Siddon, Olga K Weinberg","doi":"10.1111/ejh.14421","DOIUrl":"https://doi.org/10.1111/ejh.14421","url":null,"abstract":"<p><p>Patients with TP53 mutations in acute myeloid leukemia (AML) and blast phase myeloproliferative neoplasms (MPN-BP) experience similar poor clinical outcomes. A retrospective analysis of 39 patients with TP53 mutations (23 with AML and 16 with MPN-BP) revealed comparable mutation patterns associated with prognostic significance. A total of 47 distinct TP53 mutations were identified, including seven patients with multiple mutations. Based on clinical outcomes, we propose a two-tiered risk stratification for TP53-mutated AML and MPN-BP. The high-risk group mutations, such as splice site variants in Intron 4 (especially c.376), missense mutations in Exon 5 (notably p.R175H), and mutations in the oligomerization domain (OD), were associated with, particularly, worse overall survival (OS < 3 months). Conversely, single missense mutations in Exons 6 and 7 (notably p.Y220C, p.R248N, p.R248Q, and p.R248W), and mutations in the transactivation domain (TAD), constituted a low-risk group and were associated with relatively better prognosis (median OS: 10.15 months for the low-risk group vs. 1.3 months for the high-risk group, p < 0.0001). These findings support the hypothesis that distinct TP53 mutations can lead to varying cellular effects, therapeutic responses, and clinical outcomes. Consequently, acute myeloid neoplasms (AML and MPN-BP) harboring certain TP53 mutations may exhibit increased aggressiveness compared to other TP53 mutants, underscoring the need for prioritized clinical research and therapeutic targeting.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729499","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":"Allogeneic Haematopoietic Stem Cell Transplantation Using Reduced-Intensity Fludarabine, Busulfan and Anti-T-Lymphocyte Globulin With Strategic Donor Lymphocyte Infusion in Older Patients With Myeloid Malignancy.","authors":"Chris Armstrong, Eibhlin Conneally, Catherine Flynn, Paul Browne, Mairead Ni Chonghaile, Carmel Ann Galligan, Hayley Foy-Stones, Nicola Gardiner, Greg Lee, Nina Orfali","doi":"10.1111/ejh.14417","DOIUrl":"https://doi.org/10.1111/ejh.14417","url":null,"abstract":"<p><p>Fludarabine, busulfan, and anti-T-lymphocyte globulin (FLUBU3+ATLG) reduced-intensity conditioning is an established preparative regimen for allogeneic haematopoietic stem cell transplantation in older patients with myeloid malignancy. We examined its modern-day performance in 175 sequentially treated patients on our national programme. Overall survival was 72.4% at 2 years (95% CI 64.6%-78.6%) with a cumulative incidence of non-relapse mortality of 11%. The cumulative 2-year relapse incidence was 27% (95% CI 22.8%-37.6%) and was partially ameliorated by chronic graft-versus-host disease (HR 0.35, 95% CI 0.12-0.98, p = 0.02). Mixed donor chimerism was observed in 51.5% beyond day 90, but relapse was significantly reduced in these patients by adopting a pre-emptive donor lymphocyte infusion (DLI) strategy (HR 0.22, 95% CI 0.07-0.69, p = 0.005). The use of DLI as part of post-relapse salvage was also effective, with an improved median survival duration of 6 months in recipients (HR 0.43, 95% CI 0.18-0.98, p = 0.01). Outcomes in patients > 65 years and a limited cohort > 70 years are encouraging and compare favourably to published survival results using alternate reduced-intensity regimens. FLUBU3+ATLG, supported by modern supportive care and a pre-emptive DLI strategy, is well tolerated by older patients across a spectrum of myeloid disease with modest toxicity and favourable long-term outcomes.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729496","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":"Prognostic Significance of +1q Alterations in Relapsed/Refractory Multiple Myeloma Treated With Daratumumab-, Elotuzumab-, and Carfilzomib-Based Triplet Regimens: A Multicenter Real-World Analysis of 635 Patients.","authors":"Fortunato Morabito, Enrica Antonia Martino, Monica Galli, Massimo Offidani, Renato Zambello, Sara Bringhen, Nicola Giuliani, Catello Califano, Marino Brunori, Alfredo Gagliardi, Nicola Sgherza, Angela Maria Quinto, Gregorio Barilà, Angelo Belotti, Claudio Cerchione, Gloria Margiotta Casaluci, Raffaele Fontana, Velia Bongarzoni, Giuseppe Tarantini, Daniele Derudas, Francesca Patriarca, Alessandro Gozzetti, Adelina Sementa, Elisabetta Antonioli, Angela Rago, Flavia Lotti, Claudio De Magistris, Maria Teresa Petrucci, Loredana Pettine, Niccolò Bolli, Concetta Conticello, Elena Zamagni, Salvatore Palmieri, Maurizio Musso, Anna Mele, Roberta Della Pepa, Ernesto Vigna, Antonella Bruzzese, Francesca Fazio, Roberto Mina, Laura Paris, Iolanda Donatella Vincelli, Giuliana Farina, Clotilde Cangialosi, Katia Mancuso, Antonietta Pia Falcone, Giuseppe Mele, Antonello Sica, Sonia Morè, Giovanni Reddiconto, Giovanni Tripepi, Graziella D'Arrigo, Emiliano Barbieri, Micol Quaresima, Claudio Salvatore Cartia, Sara Pezzatti, Magda Marcatti, Francesca Farina, Anna Cafro, Michele Palumbo, Valeria Masoni, Virginia Valeria Ferretti, Francesco Di Raimondo, Pellegrino Musto, Antonino Neri, Silvia Mangiacavalli, Massimo Gentile","doi":"10.1111/ejh.14413","DOIUrl":"10.1111/ejh.14413","url":null,"abstract":"<p><p>Relapsed/refractory multiple myeloma (RRMM) research on the impact of +1q abnormalities in real-world settings is limited. This study evaluated the prognostic and predictive significance of 1q gain [gain(1q)] and amplification [ampl(1q)] in 635 RRMM patients treated with daratumumab-, elotuzumab-, and carfilzomib-based triplet regimens. Patients with +1q abnormalities had lower deep response rates [≥ CR: 9.4% for gain(1q), 11.6% for ampl(1q)] versus 20.2% in +1q-negative patients. Multivariable ordinal logistic analysis showed significantly lower odds of achieving ≥ CR in patients with gain(1q) (OR = 0.49, p < 0.001) or ampl(1q) (OR = 0.58, p = 0.0037). Progression-free survival (PFS) was longer in +1q-negative patients (28 months) compared to those with gain(1q) (8 months) or ampl(1q) (7.4 months). Multivariable models identified gain(1q) (HR = 1.9, p < 0.001) and ampl(1q) (HR = 2.2, p < 0.001) as independent negative prognostic factors alongside del17p, t(4;14), creatinine clearance < 60 mL/min, and ISS Stages II and III. Similarly, overall survival (OS) was reduced for patients with gain(1q) (25 months) and ampl(1q) (19.5 months) versus 42.2 months in +1q-negative patients. Multivariable analysis showed gain(1q) (HR = 1.6, p = 0.007) and ampl(1q) (HR = 2.0, p = 0.002) as independent predictors of increased mortality. Ancillary +1q abnormalities associated with high-risk cytogenetic changes were linked to both shorter PFS and OS. Stratification into no-hit, single-hit, double-hit, and triple-hit groups showed significant survival differences, emphasizing the impact of cumulative cytogenetic abnormalities on outcomes. In conclusion, +1q abnormalities significantly impact prognosis in RRMM and should be considered in risk stratification. The study emphasizes the importance of comprehensive cytogenetic profiling in real-world settings and highlights the need for personalized treatment strategies to improve patient outcomes.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656520","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":"Effect of NPM1 Mutation Subtype and Co-Mutation Patterns on the Outcomes of Acute Myeloid Leukemia.","authors":"Kittika Poonsombudlert, Ratdanai Yodsuwan, Sarah Mott, Kathryn Crawford, Sarah Hornberg, Anthony N Snow, Grerk Sutamtewagul, Margarida Magalhaes-Silverman, Prajwal Dhakal","doi":"10.1111/ejh.14415","DOIUrl":"https://doi.org/10.1111/ejh.14415","url":null,"abstract":"<p><strong>Introduction: </strong>NPM1 mutated AML without FLT3-ITD is considered \"favorable\" per the recent ELN 2022 criteria. However, our center has been challenged with treatment-refractory patients, prompting a search for additional prognostic factors.</p><p><strong>Methods: </strong>We reviewed records of NPM1 AML patients from 2015 to 2024. Factors associated with event-free survival (EFS) and overall survival (OS) were evaluated using Cox regression.</p><p><strong>Results: </strong>Among 141 patients with NPM1 AML, subtype A was the most common (N = 99), followed by subtype D (N = 10), subtype B (N = 6), subtype G/I/J/K/R (N = 3/5/3/2/1) and other subtypes (N = 12). Ninety patients received chemotherapy (chemo), 41 received hypomethylating agent +/- venetoclax (HMA/ven) and 10 did not receive specific anti-AML therapy. At 12 months, EFS for subtypes A, D, B, G/I/J/K/R, and other subtypes were 49%, 58%, 50%, 49%, and 31%, and OS were 71%, 79%, 50%, 44%, and 56%, respectively. Fifty patients had allogeneic stem cell transplants: 33 in CR1 and 17 in CR2+. EFS at 12 months post-HSCT was 72%. On multivariable analysis, co-mutation with KRAS (HR: 2.69, 95% CI: 1.20-6.00) or TET2 (HR: 1.99, 95% CI: 1.22-3.26) was associated with worse EFS. For each 50 k/mm³ increase in WBC at diagnosis, the risk of relapse or death increased by 21%. For OS, co-mutation with IDH1/IDH2 (HR: 0.40, 95% CI: 0.21-0.74) was associated with better OS, whereas co-mutation with SRSF2 (HR: 2.70, 95% CI: 1.35-5.40) was associated with worse OS.</p><p><strong>Conclusion: </strong>We did not find a statistically significant difference in EFS and OS among the NPM1 subtypes. However, our results showed that the prognoses of NPM1 AML can be influenced by other co-occurring mutations. A larger study is needed to confirm our findings.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656517","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":"Genomic Landscape of Mixed Phenotype Acute Leukemia Associated With Immunophenotypic Lineage Predominance: Impact on Diagnosis and Treatment","authors":"Ruifang Zheng,&nbsp;Jeffrey R. Gagan,&nbsp;Giovanni A. Botten,&nbsp;Prasad Koduru,&nbsp;Olga K. Weinberg,&nbsp;Mingyi Chen,&nbsp;Miguel D. Cantu,&nbsp;Jesse Jaso,&nbsp;Sharon Germans,&nbsp;Hung S. Luu,&nbsp;Lina Han,&nbsp;Tamra L. Slone,&nbsp;Kathryn E. Dickerson,&nbsp;Samuel John,&nbsp;Yazan F. Madanat,&nbsp;Stephen Chung,&nbsp;Robert Collins,&nbsp;Alejandro Marinos,&nbsp;Franklin Fuda,&nbsp;Weina Chen","doi":"10.1111/ejh.14414","DOIUrl":"10.1111/ejh.14414","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Mixed phenotype acute leukemia (MPAL) often poses challenges in diagnosis and clinical management. This is the first study to assess the lineage/immunophenotype-genotype association and the significance of AML-myelodysplasia-related changes (MR, cytogenetic abnormalities and gene mutations, AML-MR-CG-Gene) in MPAL classification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a clinicopathologic and genomic evaluation of 25 MPAL cases by the WHO-HEM5/ICC classification criteria, except for retaining those MPAL cases with AML-MR-CG-Gene (<i>Conditional</i>-MPAL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The majority of MPAL cases (22/25, 88%) showed distinct genotypes that overlapped with those of lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The genomic profile of ALL-like and AML-like was associated with immunophenotypically lymphoid and myeloid lineage predominance, respectively. The lineage/immunophenotype-genotype association may provide a rationale to develop a lineage-immunophenotypically/biologically guided therapy selection. Additionally, 64% of MPAL cases carried AML-MR-CG-Gene, half of which were MPAL with lymphoid-lineage predominance and had ALL-like molecular signatures, and most of these patients responded well to the ALL-based induction regimens. These results support that Conditional-MPAL with AML-MR-CG-Gene may be better diagnosed as MPAL rather than AML-MR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Genomic landscape of AML-like or ALL-like MPAL is associated with the immunophenotypic lineage predominance, and such association could impact treatment decisions and provide supporting evidence to refine MPAL diagnostic criteria in future studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"1041-1051"},"PeriodicalIF":2.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647687","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":"Central Nervous System Manifestations of Graft-Versus-Host Disease.","authors":"Nihar Desai, Niranjan Khaire, Sunu Cyriac, Aseem Saleh Alrumeh, Phedias Diamandis, Daniel M Mandell, Tommy Alfaro Moya, Eshrak Al-Shaibani, Igor Novitzky-Basso, Ivan Pasic, Arjun Datt Law, Fotios V Michelis, Rajat Kumar, Dennis Dong Hwan Kim, Jonas Mattsson, Auro Viswabandya","doi":"10.1111/ejh.14416","DOIUrl":"https://doi.org/10.1111/ejh.14416","url":null,"abstract":"","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647665","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":"Daratumumab for Posttransplant Autoimmune Hemolytic Anemia","authors":"Yaqeen Abduallah,&nbsp;Michael Kennah,&nbsp;Connor Prince,&nbsp;Ashish Masurekar,&nbsp;Natasha Kekre,&nbsp;Ram Vasudevan Nampoothiri","doi":"10.1111/ejh.14411","DOIUrl":"10.1111/ejh.14411","url":null,"abstract":"","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"1057-1059"},"PeriodicalIF":2.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647670","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":"Clinicopathological Prognostic Model for Survival in Adult Patients With Secondary Hemophagocytic Lymphohistiocytosis","authors":"Pongthep Vittayawacharin,&nbsp;Benjamin J. Lee,&nbsp;Ghayda' E'leimat,&nbsp;Yen Cao,&nbsp;Jack Reid,&nbsp;Ashley Gamayo,&nbsp;Sherif Rezk,&nbsp;Elizabeth A. Brem,&nbsp;Lisa X. Lee,&nbsp;Piyanuch Kongtim,&nbsp;Stefan O. Ciurea","doi":"10.1111/ejh.14412","DOIUrl":"10.1111/ejh.14412","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Data on bone marrow (BM) findings in secondary hemophagocytic lymphohistiocytosis (sHLH) and their association with overall survival (OS) are limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to develop a prognostic model incorporating BM findings and clinico-laboratory factors affecting OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively evaluated 50 adults with sHLH and developed a clinicopathological prognostic model based on survival-associated factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most patients demonstrated normocellular BM (46.3%) and mild hemophagocytic activity (44.2%). Factors associated with survival in multivariable analyses (MVA) were age above 70 years (hazard ratio [HR] 3.89, <i>p</i> = 0.016), infection-related (HR 4.62, <i>p</i> = 0.006), hemoglobin &lt; 7 g/dL (HR 5.21, <i>p</i> &lt; 0.001), and hypocellular marrow (HR 3.07, <i>p</i> = 0.04). A clinicopathological HLH risk model assigned 1 point to each MVA-identified survival factor, categorizing patients into low- (score 0–1), intermediate- (score 2–3), and high-risk (score 4) groups. The 6-month OS from bootstrapping internal validation among the low-, intermediate-, and high-risk groups were 84.2%, 55.6% (<i>p</i> &lt; 0.001) and 7.7% (<i>p</i> &lt; 0.001), respectively. The area under the receiver operating characteristic curve (AuROC) was 0.87.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This model stratified sHLH patients into three risk groups with distinct survival outcomes, potentially guiding future therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"1032-1040"},"PeriodicalIF":2.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633782","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":"Predictive and Prognostic Significance of Patient-Reported Outcomes for Survival and Adverse Events in Daratumumab-Treated Multiple Myeloma","authors":"Ahmad Y. Abuhelwa,&nbsp;Sara A. Almansour,&nbsp;Ethan Basch,&nbsp;Humaid O. Al-Shamsi,&nbsp;Ziad Abuhelwa,&nbsp;Yasser Bustanji,&nbsp;Mohammad H. Semreen,&nbsp;Zelal Kharaba,&nbsp;Salma M. Ali,&nbsp;Rawan Mohamed,&nbsp;Ganessan Kichenadasse,&nbsp;Ross A. McKinnon,&nbsp;Michael J. Sorich,&nbsp;Karem H. Alzoubi,&nbsp;Ashley M. Hopkins","doi":"10.1111/ejh.14410","DOIUrl":"10.1111/ejh.14410","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Patient-reported outcomes (PROs), including physical function, have predictive potential for survival but remain underexplored in multiple myeloma (MM). This study evaluates the predictive and prognostic value of PROs for treatment outcomes in MM patients on daratumumab-based therapy and evaluates physical function versus ECOG Performance Status as a potential treatment-effect modifier.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data was pooled from randomized trials (MAIA, POLLUX, CASTOR) that collected pretreatment PROs using EORTC QLQ-C30. Cox models and logistic regression examined associations between PROs and overall survival (OS), progression-free survival (PFS) and grade ≥ 3 adverse events. Physical function versus ECOG-PS was examined as a treatment effect modifier for daratumumab versus non-daratumumab therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1804 patients, 1535 (85%) had pretreatment PROs. Physical function, global health, and fatigue were most prognostic for survival and adverse events. Physical function provided independent prognostic value beyond ECOG-PS and was predictive of treatment effect. Low physical function patients experienced greater OS treatment benefit (adjusted HR (aHR) [95% CI] 0.53 [0.40–0.70], <i>p</i> interaction = 0.02) and PFS (aHR [95% CI] 0.30 [0.30–0.48], <i>p</i> interaction = 0.03) from daratumumab versus high-physical function (OS aHR 0.86 [0.62–1.19], PFS aHR 0.53 [0.42–0.67]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Physical function is a predictive and prognostic marker that complements ECOG-PS, supporting its use in informing therapy decisions for daratumumab-based treatments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"1020-1031"},"PeriodicalIF":2.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624061","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":"CLLAF SCORE—A New Risk Score for Predicting Atrial Fibrillation in Treatment-Naive CLL Patients Initiating First- and Second-Generation BTK Inhibitor Therapy","authors":"Tamar Tadmor,&nbsp;Guy Melamed,&nbsp;Hilel Alapi,&nbsp;Lior Rokach","doi":"10.1111/ejh.14400","DOIUrl":"10.1111/ejh.14400","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>One of the limiting toxicities of BTKi is the development of atrial fibrillation (AF), with an incidence of 3%–16%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to identify patients with chronic lymphocytic leukemia (CLL) starting both first- and second-generation BTKis who are at high risk of developing AF using a machine learning approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The CLL cohort is based on data obtained from electronic medical records from Maccabi, the second-largest healthcare organization in Israel. The optimal scoring model was determined using the Risk-calibrated Supersparse Linear Integer Model (RiskSLIM) algorithm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 3964 patients with a CLL diagnosis were available in the database. Of these, 208 patients started BTKi during the study period (125 on ibrutinib and 83 on acalabrutinib), and 16 patients developed AF during follow-up. In addition to well-established factors such as age, sex, and hypertension, the algorithm detected other factors associated with a high risk for AF: type of BTKi used, low eGFR, elevated absolute monocytes (&gt; 1100/μL), elevated CRP, elevated CK, and elevated B2MG (&gt; 2.5 mg/L). Based on the total AF-free survival (AFS), we identified three main risk groups: low (0–6), intermediate (7–11) and high (≥ 12). The median AF-free survival (AFS) was 28 and 56 months for the high-risk and intermediate-risk groups, respectively, and was not reached for the low-risk group. The difference between the groups was statistically significant (<i>p</i> = 0.0013).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our novel score has a high concordance index for predicting the development of AF in patients with CLL treated with first- and second-generation BTKis. It combines age, sex, medical history, and laboratory tests associated with inflammatory status and disease burden and can be applied in clinical settings worldwide.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 6","pages":"1011-1019"},"PeriodicalIF":2.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604550","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}