Blood Cancer Journal最新文献

{"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}

{"title":"Novel humanized CD19-CAR-T (Now talicabtagene autoleucel, Tali-cel™) cells in relapsed/ refractory pediatric B-acute lymphoblastic leukemia- an open-label single-arm phase-I/Ib study","authors":"Gaurav Narula, Swaminathan Keerthivasagam, Hasmukh Jain, Sachin Punatar, Akanksha Chichra, Chetan Dhamne, Prashant Tembhare, Papagudi Ganesan Subramanian, Nikhil Patkar, Minal Poojary, Anant Gokarn, Sumeet Mirgh, Nishant Jindal, Albeena Nisar, Deepali Pandit, Khushali Pandit, Alka Dwivedi, Atharva Karulkar, Ankesh Kumar Jaiswal, Aalia Khan, Shreshtha Shah, Afrin Rafiq, Moumita Basu, Juber Pendhari, Sweety Asija, Ambalika Chowdury, Ankit Banik, Nirmalya Roy Moulik, Shyam Srinivasan, Shilpushp Bhosle, Sumathi Hiregoudar, Shashank Ojha, Lingaraj Nayak, Jayshree Thorat, Bhausaheb Bagal, Manju Sengar, Navin Khattry, Shripad Banavali, Steven Highfill, Nirali N. Shah, Rahul Purwar","doi":"10.1038/s41408-025-01279-9","DOIUrl":"https://doi.org/10.1038/s41408-025-01279-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Chimeric Antigen Receptor-T (CAR-T) cell therapy is effective for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) but is not universally available. We developed a novel humanized CD19-directed CAR-T (HCAR19) approved for Phase 1/1b/2 trials. Patients aged 3–25 years were enrolled with r/r B-ALL and ineligible for allogeneic stem cell transplant. Lymphodepletion utilized standard-dose fludarabine and cyclophosphamide. A 3 + 3 design testing 3 dose-ranges was used to determine Phase-2 Dose (P2D): Dose-A, 1 × 10⁶ HCAR19 cells/kg, Dose-B, 3–5 × 10⁶/kg, and Dose-C, 10–15 × 10⁶/kg. Primary endpoint was overall response rate (ORR) at day-30 on bone-marrow flow-cytometry. From May-2021 to September-2023 12 patients [median age-14 (range: 5–24) years] were enrolled with median bone marrow blasts 19.5% at screening. Cytokine release syndrome occurred in 10 (83%) patients, predominantly Grades 1–2, and Grade-2 immune-cell associated neurotoxicity (ICANS) in 1. All patients had Grade-3 cytopenia. ORR was 91.7% (11/12), complete response (CR) in 8 (66.7%) and partial response in 3 (25%). Seven of 8 CRs were at Dose-levels B and C, all of which were sustained till 12 months follow-up. Patients who received dose levels below 3 × 10⁶/kg, or did not achieve CR, had early loss of response or rapid progression. HCAR19 demonstrated safety, manageable toxicity, and durable remissions. and P2D was determined as 5–10 × 10⁶ HCAR19-cells/kg.</p><h3 data-test=\"abstract-sub-heading\">Clinical trial registration</h3><p>The study is registered in the Clinical Trials Registry- India (CTRI/2021/05/033348 and CTRI/2023/03/050689).</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"33 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866325","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":"Dual targeting of EZH2 and EZH1 drives exit of leukemia stem cells from quiescence and potentiates chemotherapy in acute myeloid leukemia","authors":"Hiroki Akiyama, Yuki Nishida, Kyung Hee Chang, Andrea D. Bedoy, Muharrem Muftuoglu, Wencai Ma, Mahesh Basyal, Zoe Hirschi, Daisuke Honma, Shinji Tsutsumi, Jing Wang, Weiguo Zhang, Xuelin Huang, Raajit K. Rampal, Olalekan O. Oluwole, Dale Lee Bixby, Naval G. Daver, Michael Andreeff","doi":"10.1038/s41408-025-01266-0","DOIUrl":"https://doi.org/10.1038/s41408-025-01266-0","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"7 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866324","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":"Immune profiling of smoldering multiple myeloma patients treated in a phase lb study of PVX-410 vaccine targeting XBP1/CD138/CS1 antigens, and citarinostat, a histone deacetylase inhibitor (HDACi) with and without lenalidomide","authors":"Diana Cirstea, Rajib Shome, Mehmet Samur, Srikanth Talluri, Joseph J. Connolly, Alexandra Jean Wright, Emilie Duvallet, Amanda N. R. Joyce, Kathleen Lively, Gina Basinsky, Andrew J. Yee, Cristiana Costa Chase, Ehsan Malek, Ruben Niesvizky, Paul G. Richardson, Noopur S. Raje","doi":"10.1038/s41408-025-01272-2","DOIUrl":"https://doi.org/10.1038/s41408-025-01272-2","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"71 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866323","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":"Effect of Intravenous Immunoglobulin (IVIG) Supplementation on infection-free survival in recipients of BCMA-directed bispecific antibody therapy for multiple myeloma","authors":"Meera Mohan, Aniko Szabo, Heloise Cheruvalath, Anna Clennon, Vineel Bhatlapenumarthi, Anannya Patwari, Metodi Balev, Divaya Bhutani, Asis Shrestha, Sharmilan Thanendrarajan, Binod Dhakal, Maurizio Zangari, Anup Trikannad, Sruthi Vellanki, Samer Al-Hadidi, Suzanne Lentzsch, Frits van Rhee, Aishee Bag, Anita D’Souza, Nishi Shah, Rajshekhar Chakraborty, Mansi R. Shah, Carolina Schinke","doi":"10.1038/s41408-025-01282-0","DOIUrl":"https://doi.org/10.1038/s41408-025-01282-0","url":null,"abstract":"<p>The main objective of this multi-institutional study is to understand the effect of primary intravenous immunoglobulin (IVIG) replacement on clinical outcomes in recipients of BCMA-directed bispecific antibody (bsAb), where infection remains an important cause of morbidity and mortality. This is a retrospective study of patients treated with either standard of care teclistamab or BCMA-directed investigational bsAb between Nov 2017 and Dec 2023. Primary IVIG prophylaxis was defined as starting IVIG prior to first documented infection. All analyses were adjusted for immortal-time bias inherent in this grouping. A total of 225 patients were included in this analysis. Primary IVIG prophylaxis was defined as starting IVIG prior to first documented infection. The median follow-up of patients treated with and without primary IVIG prophylaxis was, 9 and 11 months, respectively. The cumulative incidence of all grade infections at 12 months with and without primary IVIG prophylaxis were 56% (95%CI 40%,78%) and 60% (95% CI 48%, 76%); <i>p</i> = 0.72, respectively. The 12-month cumulative incidence of ≥ grade 3 infections was 35% (95% CI 21%, 57%) with primary IVIG prophylaxis and 45% (95% CI 34%, 60%) without; <i>p</i> = 0.37. The median infection free survival (IFS) for all-grade infections was 7.7 (95% CI 3.3, 14) months with primary IVIG prophylaxis and 3 (95% CI 2.6, 4.5) months without (<i>p</i> = 0.021). The median ≥ grade 3 IFS was 14 (95% CI 8.8, NR) and 7.5 (95% CI 6.1, 14) months, with and without primary IVIG respectively; <i>p</i> = 0.022. Patients on primary IVIG prophylaxis had a superior progression-free-survival (PFS) [median PFS 15 vs 8 months; <i>p</i> = 0.026] and overall-survival (OS) [median OS 16 vs 44 months; <i>p</i> = 0.007]. On multivariate analysis, primary IVIG prophylaxis was independently associated with improved OS (HR = 0.37; <i>p</i> = 0.021), while the presence of extra-medullary (HR = 2.71; <i>p</i> = &lt;0.001) and high-risk disease (HR = 1.88; <i>p</i> = 0.031) conferred poor outcomes. In recipients of BCMA-directed bsAb, IVIG supplementation was associated with an improved clinical outcome, including favorable IFS and OS.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"19 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866326","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":"Establishing measurable residual disease trajectories for patients on treatment for newly diagnosed multiple myeloma as benchmark for deployment of T-cell redirection therapy","authors":"Susan Bal, Tylan Magnusson, Gayathri Ravi, Smith Giri, Kelly Godby, Binod Dhakal, Natalie S. Callander, Rebecca W. Silbermann, Bhagirathbhai Dholaria, Vishnu B. Reddy, Luciano J. Costa","doi":"10.1038/s41408-025-01252-6","DOIUrl":"https://doi.org/10.1038/s41408-025-01252-6","url":null,"abstract":"<p>Autologous stem cell transplantation (ASCT) has been the prime consolidative strategy to increase the depth and duration of response in newly diagnosed multiple myeloma (NDMM), albeit with short- and long-term toxicities. Minimal residual disease (MRD) is an important early response endpoint correlating with clinically meaningful outcomes and may be used to isolate the effect of ASCT. We report the impact of ASCT on MRD burden and generate a benchmark for evaluation of novel treatments as consolidation. We collected MRD by next generation sequencing (NGS; clonoSEQ®) post induction and post-ASCT in consecutive patients (<i>N</i> = 330, quadruplet, <i>N</i> = 279; triplet, <i>N</i> = 51). For patients receiving quadruplets, MRD &lt; 10⁻⁵ post-induction was 29% (MRD &lt; 10⁻⁶ 15%) increasing to 59% post-ASCT (MRD &lt; 10⁻⁶ 45%). Among patients with MRD &gt; 10⁻⁵ post-induction, ASCT lowered the MRD burden&gt;1 log₁₀ for 69% patients. The use of quadruplet induction (vs. triplet) did not reduce the effect of ASCT on MRD burden. Reduction in MRD burden with ASCT was most pronounced in patients with high-risk chromosome abnormalities.</p><p>This dataset provides granular data to delineate the impact of ASCT on MRD as legacy consolidative strategy in NDMM and provides an important benchmark for evaluation of efficacy of TCRT as experimental consolidative strategy.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"1 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862954","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":"Basophilia and eosinophilia in primary myelofibrosis: phenotype, genotype, and prognostic correlates","authors":"Sarah Dingli, Saubia Fathima, Priyansh Faldu, Naseema Gangat, David Dingli, Ayalew Tefferi","doi":"10.1038/s41408-025-01285-x","DOIUrl":"https://doi.org/10.1038/s41408-025-01285-x","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"49 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853254","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":"Comment on: \"Switching TKIs during CML therapy is frequent, mostly driven by intolerance, and does not affect survival: a prospective Quebec registry study\" by Busque et al.","authors":"Ahmet Emre Eşkazan","doi":"10.1038/s41408-025-01288-8","DOIUrl":"https://doi.org/10.1038/s41408-025-01288-8","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"32 1","pages":"70"},"PeriodicalIF":12.8,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851052","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}