Blood Cancer Journal最新文献

{"title":"Validation of the 5th edition of the World Health Organization and International Consensus Classification guidelines for TP53-mutated myeloid neoplasm in an independent international cohort","authors":"Mithun Vinod Shah, Kevin Hung, Anmol Baranwal, Gauri Wechalekar, Aref Al-Kali, Carla R. Toop, Patricia Greipp, Monika M. Kutyna, Aasiya Matin, Dariusz Ladon, Antoine Saliba, Dong Chen, Kebede Begna, Anna Brown, Danielle Rud, Mark R. Litzow, William J. Hogan, Peter Bardy, Talha Badar, Sharad Kumar, David T. Yeung, Mrinal M. Patnaik, James M. Foran, Rong He, Naseema Gangat, Mehrdad Hefazi, Hamish S. Scott, Cecilia Y. Arana Yi, Hassan Alkhateeb, Abhishek A. Mangaonkar, Daniel Thomas, Christopher N. Hahn, Attilio Orazi, Daniel A. Arber, Chung Hoow Kok, Ayalew Tefferi, Devendra Hiwase","doi":"10.1038/s41408-025-01290-0","DOIUrl":"https://doi.org/10.1038/s41408-025-01290-0","url":null,"abstract":"<p>The World Health Organization (WHO-5) and International Consensus Classification (ICC) acknowledge the poor prognosis of <i>TP53</i>-mutated (<i>TP53</i>^mut) myeloid neoplasm (MN). However, there are substantial differences between the two classifications that may lead to under- or overestimation of the prognostic risk. We retrospectively applied WHO-5 and ICC to 603 MN cases harboring <i>TP53</i>^mut (variant allele frequency, VAF ≥ 2%). WHO-5 and ICC would not classify 64% and 20% of these cases as <i>TP53</i>^mut MN, respectively. Moreover, of those classified, 67.5% would be classified discrepantly. Primary drivers of discrepancies included: (i) prognostic importance of <i>TP53</i>^mut acute myeloid leukemia (AML), (ii) interaction of the blast percentage and allelic status, (iii) 17p.13.1 deletion detected by cytogenetics, (iv) complex karyotype (CK) as multi-hit equivalent, and (v) <i>TP53</i>^mut VAF threshold, we analyzed survival outcomes of each of these groups with an aim to provide clarity. <i>TP53</i>^mut AML was associated with significantly poor survival compared to <i>TP53</i>-wild type <i>TP53</i>^wt AML, myelodysplasia-related (AML, MR 4.7 <i>vs</i>. 18.3 months; <i>P</i> &lt; 0.0001), supporting its inclusion within <i>TP53</i>^mut MN as a distinct subentity. Secondly, the survival of <i>TP53</i>^mut with blast 10–19% was poor regardless of the allelic status. Thirdly, for cases with a single <i>TP53</i>^mut with VAF &lt; 50%, 17p13.1 del or CK serve as practical surrogates of biallelic inactivation, obviating the need for an additional copy number analysis. Finally, <i>TP53</i>^mut AML, MDS multi-hit/multi-hit equivalent with VAF &lt; 10% had significantly poorer survival compared to <i>TP53</i>^mut MDS VAF &lt; 10% without CK and 17p del, and were comparable to those with VAF ≥ 10% (14.1 <i>vs</i>. 48.8 <i>vs</i>.7.8 months, <i>P</i> &lt; 0.0001). Collectively, these findings address key areas of contention and provide valuable insights that will guide future revisions of the WHO and ICC classifications.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transposable elements as genome regulators in normal and malignant haematopoiesis.","authors":"Dmitry Prokopov,Hale Tunbak,Eve Leddy,Bryce Drylie,Francesco Camera,Özgen Deniz","doi":"10.1038/s41408-025-01295-9","DOIUrl":"https://doi.org/10.1038/s41408-025-01295-9","url":null,"abstract":"Transposable elements (TEs) constitute over half of the human genome and have played a profound role in genome evolution. While most TEs have lost the ability to transpose, many retain functional elements that serve as drivers of genome innovation, including the emergence of novel genes and regulatory elements. Recent advances in experimental and bioinformatic methods have provided new insights into their roles in human biology, both in health and disease. In this review, we discuss the multifaceted roles of TEs in haematopoiesis, highlighting their contributions to both normal and pathological contexts. TEs influence gene regulation by reshaping gene-regulatory networks, modulating transcriptional activity, and creating novel regulatory elements. These activities play key roles in maintaining normal haematopoietic processes and supporting cellular regeneration. However, in haematological malignancies, TE reactivation can disrupt genomic integrity, induce structural variations, and dysregulate transcriptional programmes, thereby driving oncogenesis. By examining the impact of TE activity on genome regulation and variation, we highlight their pivotal roles in both normal haematopoietic processes and haematological cancers.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"47 1","pages":"87"},"PeriodicalIF":12.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biobanking and consent to future biospecimen use among adults enrolled in SWOG trials from 2000 to 2024.","authors":"Daniel J Olivieri,Alexis Berridge-Green,Megan Othus,Jerald P Radich,Anjali S Advani,Harry P Erba,Roland B Walter","doi":"10.1038/s41408-025-01294-w","DOIUrl":"https://doi.org/10.1038/s41408-025-01294-w","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"20 1","pages":"85"},"PeriodicalIF":12.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of acute myeloid leukemia with KMT2A (MLL) rearrangement: a multicenter study of TROPHY group","authors":"Ruoxuan Zhang, Huihong Huang, Yi Zhang, Yi Xia, Jiayu Huang, Chuanhe Jiang, Luxiang Wang, Haiyang Lu, Zengkai Pan, Gaoxiang Wang, Yang Yang, Yilei Ma, Xiaodong Mo, Wei Shi, Xiaoxia Hu, Yang Cao","doi":"10.1038/s41408-025-01293-x","DOIUrl":"https://doi.org/10.1038/s41408-025-01293-x","url":null,"abstract":"<p>Acute myeloid leukemia (AML) with <i>KMT2A</i> rearrangement (<i>KMT2A</i>-r) is associated with poor prognosis, but the benefit of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for <i>KMT2A</i>-r AML is unclear. We reviewed adult AML patients treated within the TROPHY group and identified 292 cases of <i>KMT2A</i>-r AML, 254 (87.0%) of whom achieved first complete remission (CR1) and 192 (75.6%) of CR1 patients underwent allo-HSCT. We show that allo-HSCT is an independent favorable prognostic factor in CR1 patients for both overall survival (OS) (hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.45–0.69, <i>P</i> &lt; 0.001) and cumulative incidence of relapse (CIR) (HR = 0.01, 95% CI: 0.005–0.04, <i>P</i> &lt; 0.001). Among allo-HSCT recipients, survival outcomes were comparable between patients with <i>KMT2A::MLLT3</i> and those with other 11q23/<i>KMT2A</i> rearrangements (3-year OS: 74.3% vs. 77.5%, <i>P</i> = 0.97; 3-year event-free survival [EFS]: 55.2% vs. 62.2%, <i>P</i> = 0.34; 3-year CIR: 24.4% vs. 20.8%, <i>P</i> = 0.32). Both multiparameter flow cytometry-based measurable residual disease (MFC-MRD) and <i>KMT2A</i>-r MRD determined by quantitative PCR prior to allo-HSCT were associated with worse transplant outcomes. Multivariable analysis identified detectable <i>KMT2A</i>-r MRD at allo-HSCT as a significant risk factor for reduced EFS (HR = 2.46, 95% CI: 1.32–4.60, <i>P</i> = 0.005). These findings confirm the survival benefit of allo-HSCT in adult patients with <i>KMT2A</i>-r AML and underscore the prognostic value of <i>KMT2A</i>-r MRD prior to transplantation.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"8 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD56 expression modulates NAD+ metabolic landscape and predicts sensitivity to anti-CD38 therapies in multiple myeloma","authors":"Giulia Giorgetti, Elena Maroto-Martin, Debora Soncini, Daniela Fenoglio, Pamela Becherini, Andrea Benzi, Silvia Ravera, Isabella Traverso, Francesco Ladisa, Francesco Lai, Giulia Rivoli, Dario Truffelli, Aimable Nahimana, Antonia Cagnetta, Fabio Guolo, Chiara R. M. Uras, Anaïs Schavgoulidze, Jessica Fong Ng, Alessio Nencioni, Santina Bruzzone, Nikhil C. Munshi, Roberto Massimo Lemoli, Mariateresa Fulciniti, Michele Cea","doi":"10.1038/s41408-025-01284-y","DOIUrl":"https://doi.org/10.1038/s41408-025-01284-y","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"111 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Superior survival in diffuse large B cell lymphoma of the bone with immune rich tumor microenvironment","authors":"Ruben A. L. de Groen, Fleur A. de Groot, Stefan Böhringer, Esther J. Kret, Lorraine M. de Haan, Troy Noordenbos, Susan Blommers, Romée E. W. Jansen, Tom van Wezel, Ronald van Eijk, Richard Raghoo, Dina Ruano, Liane te Boome, Valeska Terpstra, Henriette Levenga, Els Ahsmann, Eduardus F. M. Posthuma, Isabelle Focke-Snieders, Lizan Hardi, Wietske C. E. den Hartog, Anke van den Berg, Pim Mutsaers, King Lam, Marjolein W. M. van der Poel, Myrurgia Abdul Hamid, F. J. Sherida H. Woei-A-Jin, Ann Janssens, Thomas Tousseyn, Judith V. M. G. Bovée, Lianne Koens, Arjan Diepstra, Arjen H. G. Cleven, Marie José Kersten, Patty M. Jansen, Hendrik Veelken, Marcel Nijland, Tim J. A. Dekker, Joost S. P. Vermaat","doi":"10.1038/s41408-025-01291-z","DOIUrl":"https://doi.org/10.1038/s41408-025-01291-z","url":null,"abstract":"<p>With tumor genomic and gene-expression profiling (GEP), this study investigated the immune-molecular signatures of a unique cohort of diffuse large B-cell lymphoma of the bone (bone-DLBCL), including primary bone (PB-DLBCL, <i>n</i> = 52) and polyostotic-DLBCL (<i>n</i> = 20), in comparison to nodal DLBCLs with germinal center B-cell (GCB) phenotype (nodal-DLBCL-GCB, <i>n</i> = 34). PB-DLBCL and polyostotic-DLBCL shared similar genomic profiles and transcriptomic signatures, justifying their collective analysis as bone-DLBCL. Differential incidences of <i>EZH2</i>, <i>HIST1H1E</i>, and <i>MYC</i> aberrations (<i>p</i> &lt; 0.05) confirmed the distinct oncogenic evolution between bone-DLBCL and nodal-DLBCL-GCB. Differentially expressed genes were identified between bone-DLBCL and nodal-DLBCL-GCB (<i>p</i> &lt; 0.001), substantiated by distinct gene-set enrichment analysis (GSEA). In contrast to a more ‘depleted’ phenotype for nodal-DLBCL-GCB, bone-DLBCL primarily exhibited an ‘intermediate/rich’ tumor microenvironment (TME) signature (<i>p</i> = 0.001), as determined by a previously published gene set. Unsupervised clustering defined two distinct groups that aligned with previously reported immune-enriched TME clusters: an ‘immune-rich’ cluster largely consisting of bone-DLBCLs (75%, <i>p</i> = 0.002) with superior survival (<i>p</i> = 0.030), and a poor-prognostic ‘immune-low’ cluster, including mostly nodal-DLBCL-GCB (61%). Single-sample (ss)GSEA showed higher scores for regulatory T cells, immunosuppressive/prolymphoma cytokines, and vascular endothelial cells in immune-rich samples (<i>p</i> &lt; 0.001). Additionally, CIBERSORTx revealed a higher abundance of regulatory T cells and activated mast cells in the immune-rich cluster (<i>p</i> &lt; 0.001). These findings were confirmed at protein level, where CD3 and FOXP3 immunochemistry showed significant overlap with the gene-expression data (<i>p</i> &lt; 0.001). Conclusively, PB-DLBCL and polyostotic-DLBCL share immune-molecular TME characteristics, supporting their classification as a unified bone-DLBCL entity. The distinct immune-rich TME profile of bone-DLBCL associated with superior survival potentially shapes emerging immunomodulatory strategies</p><figure></figure>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"46 12 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective phase II trial of first-line rituximab, methotrexate, and orelabrutinib (R-MO) in primary central nervous system lymphoma","authors":"Lixia Sheng, Hailing Liu, Xiaohui Zhang, Kaiyang Ding, Jie Ma, Hongling Peng, Xia Zhao, Mei Sun, Wei Shi, Feiyan Zhang, Jianyong Li, Lei Cao, Lei Fan","doi":"10.1038/s41408-025-01278-w","DOIUrl":"https://doi.org/10.1038/s41408-025-01278-w","url":null,"abstract":"<p>The treatment of primary central nervous system lymphoma (PCNSL) is currently limited by the impermeability of the blood-brain barrier. This study aims to assess the efficacy and safety of the R-MO regimen (rituximab, high-dose methotrexate, and orelabrutinib) in the treatment of patients with newly diagnosed PCNSL. A total of 37 patients were enrolled in this prospective, multi-center phase II trial. The post-induction overall response rate (ORR) was 90.3%, and the complete response rate (CRR) was 87.1%. Throughout the trial, the best ORR was 97.1%, and the best CRR was 94.1%. With a median follow-up of 12.6 months, the median progression-free survival (PFS) was not reached, with a 1-year PFS rate of 83.6%, meeting the primary study endpoint. The 1-year overall survival rate was 89.6%. Notably, there was no significant difference in PFS between transplanted and non-transplanted groups (<i>P</i> = 0.226). The most common adverse events were neutropenia, lymphocytopenia, and infections, each occurring in 45.9% of patients. Overall, the addition of orelabrutinib to high-dose methotrexate and rituximab in newly diagnosed PCNSL patients has demonstrated promising outcomes and favorable safety profiles, advocating for the use of this combination therapy as a potential frontline treatment option for PCNSL.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"39 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revised free light chain reference intervals enhance risk stratification in monoclonal gammopathy of undetermined significance and reduce overdiagnosis","authors":"Cecilie Velsoe Maeng, Sæmundur Rögnvaldsson, Thórir Einarsson Long, Christian Brieghel, Emil Hermansen, Carsten Utoft Niemann, Kirsten Grønbæk, Sigurður Yngvi Kristinsson, Sigrún Thorsteinsdóttir","doi":"10.1038/s41408-025-01289-7","DOIUrl":"https://doi.org/10.1038/s41408-025-01289-7","url":null,"abstract":"<p>The free light chain (FLC) ratio is a critical part of risk stratification for monoclonal gammopathy of undetermined significance (MGUS). Recently, revised FLC reference intervals developed using the iStopMM cohort, accounting for age and renal function, have reduced the rate of abnormal findings. Here, we examine the implications of the revision in an independent Danish MGUS cohort. Of 6993 MGUS individuals, 2641 had an abnormal FLC ratio by the original intervals, of whom 844 (32%) were reclassified as normal using the revised intervals. Reclassified individuals had no significantly increased risk of progression compared to those with a normal FLC ratio (hazard ratio (HR): 1.07, 95% confidence interval (CI) 0.74–1.57). Those with an abnormal FLC ratio by the revised reference intervals had an increased risk of progression (HR 2.23, 95% CI 1.79–2.78). Using the revised reference intervals, 490 individuals (16%) were reclassified to low-risk from a higher risk group. These individuals had a similar progression risk compared to others in the low-risk group. The findings validate the revised FLC reference intervals, enhancing prognostic accuracy and improving risk stratification to accurately identify MGUS individuals at risk of progression while reducing unnecessary classifications as high-risk.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"12 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 6-tsRNA signature for early detection, treatment response monitoring, and prognosis prediction in diffuse large B cell lymphoma","authors":"Jun Rao, Lin Xia, Qiong Li, NaYa Ma, Xinlei Li, Jiali Li, Lidan Zhu, Pan Zhao, Yunjing Zeng, Sha Zhou, Huanping Guo, Shijia Lin, Song Dong, Shifeng Lou, Fangyi Fan, Jin Wei, Jiang F. Zhong, Li Gao, Shengwen Calvin Li, Xi Zhang","doi":"10.1038/s41408-025-01267-z","DOIUrl":"https://doi.org/10.1038/s41408-025-01267-z","url":null,"abstract":"<p>Diffuse large B-cell lymphoma (DLBCL) presents considerable clinical challenges due to its aggressive nature and diverse clinical progression. New molecular biomarkers are urgently needed for outcome prediction. We analyzed blood samples from DLBCL patients and healthy individuals using short, non-coding RNA sequencing. A classifier based on six tsRNAs was developed through random forest and primary component analysis. This classifier, established using Cox proportional hazards modeling with repeated 10-fold cross-validation on an internal cohort of 100 samples analyzed using RT-qPCR, effectively identified high-risk patients with significantly lower overall survival compared to low-risk patients (Hazard ratio: 6.657, 95%CI 2.827-15.68, <i>P</i> = 0.0006). Validation in an external cohort of 160 samples using RT-qPCR confirmed the classifier’s robust performance. High-risk status was strongly associated with disease histological subtype, stage, and International Prognostic Index scores. Integration of the classifier into the IPI model enhanced the precision and consistency of prognostic predictions. A dynamic study revealed that patients experiencing a 1.06-fold decrease after one therapy cycle (early molecular response) exhibited better treatment outcomes and prognosis. Furthermore, the 6-tsRNA signature accurately differentiated healthy individuals from DLBCL (AUC 0.882, 95%CI 0.826-0.939). These findings underscore the potential of the identified 6-tsRNA profile as a biomarker for monitoring treatment effectiveness and predicting DLBCL outcomes.</p><figure></figure>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"82 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of POD24 as a robust early clinical indicator of poor survival in mantle cell lymphoma from 1280 patients on clinical trials, a LYSA study","authors":"Clémentine Sarkozy, Loïc Chartier, Vincent Ribrag, Remy Gressin, Christian H. Geisler, Hanneke C. Kluin-Nelemans, Catherine Thieblemont, Franck Morschhauser, François Lemonnier, Violaine Safar, Benoît Tessoulin, Lucie Oberic, Ghandi Damaj, Hervé Ghesquières, Krimo Bouabdallah, René Olivier Casasnovas, Roch Houot, Wolfram Klapper, Barbara Burroni, Christiane Pott, Marie-Hélène Delfau-Larue, Elizabeth Macintyre, Mary Callanan, Mats Jerkeman, Michael Unterhalt, Eva Hoster, Martin Dreyling, Steven Le Gouill, Olivier Hermine, Morgane Cheminant","doi":"10.1038/s41408-025-01241-9","DOIUrl":"https://doi.org/10.1038/s41408-025-01241-9","url":null,"abstract":"<p>In mantle cell lymphoma, early progression of disease has been associated with short overall survival. The impact of clinical, pathological, and treatment strategies on the risk of early relapse has not been assessed in a large cohort of patients. We performed a pooled analysis of patients recruited in France from six randomized first-line MCL trials. Among 1386 treated MCL patients, 1280 were evaluable for POD24 status: 299 (23.4%) with a POD24 event and 981 (76.6%) without. Patients with a POD24 event had a median OS of 9.3 months (95% CI 8.4–11.8) versus not reached (95% CI 97.8–NR) for those without POD24 events. The median post-relapse OS of patients with a late relapse was also significantly longer at 49.4 months (HR = 0.39; 95% CI 0.31–0.48; <i>P</i> &lt; 0.001) as compared to POD24 patients. Baseline variables (age, performance status, B symptoms, LDH/ULN, leukocytes, blastoid variant, and Ki-67 &gt; 30%) were significantly associated with the risk of POD24, independent of ASCT. Among responding patients at end-of-induction (<i>n</i> = 1105) who had received ASCT, anti-CD20 maintenance was associated with a decreased risk of POD24 (OR = 0.37; 95% CI 0.1–1.0). Using this large data set of patients in clinical trials, we confirm that POD24 status is strongly associated with subsequent OS in MCL. Rituximab maintenance provided significant protection against the risk of POD24, independent of ASCT. Progression within 2 years should be considered as a primary endpoint in future studies.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"70 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}