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Outcomes and prognostic impact of trisomy 8 in acute myeloid leukemia patients treated with intensive chemotherapy 急性髓系白血病强化化疗患者8三体的预后及预后影响
IF 12.8 1区 医学
Blood Cancer Journal Pub Date : 2025-08-28 DOI: 10.1038/s41408-025-01332-7
Daniel Tuyet Kristensen, Rasmus Froberg Brøndum, Michael Knudsen, Marianne Tang Severinsen, Lykke Grubach, Mette Klarskov Andersen, Jack B. Cowland, Vibe Skov, Birgitte Preiss, Dorthe Ørnskov, Estrid Høgdall, Tim Svenstrup Poulsen, Eigil Kjeldsen, Marie Bill, Hans Beier Ommen, Andreas Due Ørskov, Claudia Schöllkopf, Jakob Werner Hansen, Kirsten Grønbæk, Claus Werenberg Marcher, Dennis Lund Hansen, Ole Halfdan Larsen, Martin Bøgsted, Anne Stidsholt Roug
{"title":"Outcomes and prognostic impact of trisomy 8 in acute myeloid leukemia patients treated with intensive chemotherapy","authors":"Daniel Tuyet Kristensen, Rasmus Froberg Brøndum, Michael Knudsen, Marianne Tang Severinsen, Lykke Grubach, Mette Klarskov Andersen, Jack B. Cowland, Vibe Skov, Birgitte Preiss, Dorthe Ørnskov, Estrid Høgdall, Tim Svenstrup Poulsen, Eigil Kjeldsen, Marie Bill, Hans Beier Ommen, Andreas Due Ørskov, Claudia Schöllkopf, Jakob Werner Hansen, Kirsten Grønbæk, Claus Werenberg Marcher, Dennis Lund Hansen, Ole Halfdan Larsen, Martin Bøgsted, Anne Stidsholt Roug","doi":"10.1038/s41408-025-01332-7","DOIUrl":"https://doi.org/10.1038/s41408-025-01332-7","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"27 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915677","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}
引用次数: 0
18F-FDG brain/cerebellum-to-liver ratios as prognostic factors. 18F-FDG脑/小脑-肝比值作为预后因素。
IF 11.6 1区 医学
Blood Cancer Journal Pub Date : 2025-08-27 DOI: 10.1038/s41408-025-01357-y
David Morland, Eric Durot
{"title":"18F-FDG brain/cerebellum-to-liver ratios as prognostic factors.","authors":"David Morland, Eric Durot","doi":"10.1038/s41408-025-01357-y","DOIUrl":"https://doi.org/10.1038/s41408-025-01357-y","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"15 1","pages":"145"},"PeriodicalIF":11.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Who truly benefits from gilteritinib combinations in FLT3-mutated relapsed-refractory(R/R) AML: a Canadian single center analysis 谁真正受益于gilteritinib联合治疗flt3突变的复发难治性AML (R/R):加拿大单中心分析
IF 12.8 1区 医学
Blood Cancer Journal Pub Date : 2025-08-26 DOI: 10.1038/s41408-025-01353-2
Akhil Rajendra, Elliot Smith, Maria Agustina Perusini, Kenny Tang, Eshetu G. Atenafu, Aniket Bankar, Steven Chan, Marta B. Davidson, Vikas Gupta, Dawn Maze, Mark D. Minden, Guillaume Richard-Carpentier, Aaron D. Schimmer, Andre C. Schuh, Karen Yee, Hassan Sibai
{"title":"Who truly benefits from gilteritinib combinations in FLT3-mutated relapsed-refractory(R/R) AML: a Canadian single center analysis","authors":"Akhil Rajendra, Elliot Smith, Maria Agustina Perusini, Kenny Tang, Eshetu G. Atenafu, Aniket Bankar, Steven Chan, Marta B. Davidson, Vikas Gupta, Dawn Maze, Mark D. Minden, Guillaume Richard-Carpentier, Aaron D. Schimmer, Andre C. Schuh, Karen Yee, Hassan Sibai","doi":"10.1038/s41408-025-01353-2","DOIUrl":"https://doi.org/10.1038/s41408-025-01353-2","url":null,"abstract":"<figure></figure>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"142 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899263","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}
引用次数: 0
Optimization and validation of the international metabolic prognostic index for CD19 CAR-T in large B-cell lymphoma CD19 CAR-T在大b细胞淋巴瘤中的国际代谢预后指标的优化和验证
IF 12.8 1区 医学
Blood Cancer Journal Pub Date : 2025-08-26 DOI: 10.1038/s41408-025-01338-1
Michael Winkelmann, Sandeep S. Raj, Michael D. Jain, Gloria Iacoboni, Fabian Müller, Leo Hansmann, Magdalena Corona, Alejandro Luna, Khushali Jhaveri, Gunjan L. Shah, Michael Scordo, Turab Mohammad, Erin A. Dean, Gabriel T. Sheikh, Wolfgang G. Kunz, Tobias Tix, Veit L. Bücklein, Akshay Bedmutha, Doris Leithner, Michael von Bergwelt-Baildon, Alexander P. Boardman, M. Lia Palomba, Jae H. Park, Gilles Salles, Miguel-Angel Perales, Heiko Schöder, Marion Subklewe, Pere Barba, Frederick L. Locke, Roni Shouval, Kai Rejeski
{"title":"Optimization and validation of the international metabolic prognostic index for CD19 CAR-T in large B-cell lymphoma","authors":"Michael Winkelmann, Sandeep S. Raj, Michael D. Jain, Gloria Iacoboni, Fabian Müller, Leo Hansmann, Magdalena Corona, Alejandro Luna, Khushali Jhaveri, Gunjan L. Shah, Michael Scordo, Turab Mohammad, Erin A. Dean, Gabriel T. Sheikh, Wolfgang G. Kunz, Tobias Tix, Veit L. Bücklein, Akshay Bedmutha, Doris Leithner, Michael von Bergwelt-Baildon, Alexander P. Boardman, M. Lia Palomba, Jae H. Park, Gilles Salles, Miguel-Angel Perales, Heiko Schöder, Marion Subklewe, Pere Barba, Frederick L. Locke, Roni Shouval, Kai Rejeski","doi":"10.1038/s41408-025-01338-1","DOIUrl":"https://doi.org/10.1038/s41408-025-01338-1","url":null,"abstract":"<p>While CD19-directed CAR T-cell therapy represents a transformative immunotherapy for relapsed/refractory large B-cell lymphoma (r/r LBCL), more than 50% of patients ultimately progress or relapse. Recently, the International Metabolic Prognostic Index (IMPI) – incorporating age, stage, and metabolic tumor volume (MTV) – was shown to improve prognostication for LBCL frontline treatment. Here, we examine its utility to predict toxicity and survival in CAR-T recipients. This multicenter observational study spanning six international sites included 504 patients with available <sup>18</sup>FDG-PET/CT imaging at last response assessment prior to lymphodepletion. Optimal CAR-adapted MTV thresholds were identified in a development cohort (<i>n</i> = 256) and incorporated into a CAR-T-specific IMPI (“CAR-IMPI”). The prognostic performance of CAR-IMPI was validated in an independent cohort (<i>n</i> = 248). CAR-IMPI risk categories, defined by the median (1.35) and terciles (1.07, 1.58), demonstrated significant discrimination for progression-free survival (PFS; <i>p</i> &lt; 0.0001) and overall survival (OS; <i>p</i> &lt; 0.0001) in both cohorts. Multivariate Cox regression confirmed CAR-IMPI as an independent predictor of survival, accounting for pre-lymphodepletion LDH and CRP, performance status, treatment center, and CAR-T product. Patients in the CAR-IMPI high-risk category experienced increased severity of CRS and ICANS, and higher rates of intensive care unit (ICU) admissions. In an exploratory analysis, combining CAR-IMPI with established indices of high-risk systemic inflammation (CAR-HEMATOTOX, InflaMix) further enhanced survival stratification. The CAR-IMPI may provide a potent and validated PET-based tool for risk stratification of clinical outcomes in patients with r/r LBCL receiving CD19 CAR-T therapy. Our data highlight the utility of combining clinical and radiological modalities, with implications for patient selection and the anticipated level-of-care for toxicity management.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"7 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899264","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}
引用次数: 0
Allogeneic stem cell transplantation from variant-carrying family donors leads to long-term engraftment in Telomere Biology Disorders 来自携带变异的家族供体的同种异体干细胞移植导致端粒生物学疾病的长期植入
IF 12.8 1区 医学
Blood Cancer Journal Pub Date : 2025-08-25 DOI: 10.1038/s41408-025-01348-z
Nergis Güzel, Yannic Schumacher, Kim Kricheldorf, Margherita Vieri, Martin Kirschner, Anne-Claire Gerhard-le Gars, Jens Panse, Mareike Tometten, Jeanette Walter, Andrea Gehrig, Erdmute Kunstmann, Laura Holthöfer, Susann Schweiger, Daniel Wolff, Florian Kraft, Miriam Elbracht, Ingo Kurth, Tim H. Brümmendorf, Robert Meyer, Fabian Beier
{"title":"Allogeneic stem cell transplantation from variant-carrying family donors leads to long-term engraftment in Telomere Biology Disorders","authors":"Nergis Güzel, Yannic Schumacher, Kim Kricheldorf, Margherita Vieri, Martin Kirschner, Anne-Claire Gerhard-le Gars, Jens Panse, Mareike Tometten, Jeanette Walter, Andrea Gehrig, Erdmute Kunstmann, Laura Holthöfer, Susann Schweiger, Daniel Wolff, Florian Kraft, Miriam Elbracht, Ingo Kurth, Tim H. Brümmendorf, Robert Meyer, Fabian Beier","doi":"10.1038/s41408-025-01348-z","DOIUrl":"https://doi.org/10.1038/s41408-025-01348-z","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"111 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899265","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}
引用次数: 0
Venetoclax and azacitidine for molecular relapse after intensive chemotherapy in NPM1 or CBF AML: a FILO study Venetoclax和阿扎胞苷治疗NPM1或CBF AML强化化疗后分子复发:一项FILO研究
IF 12.8 1区 医学
Blood Cancer Journal Pub Date : 2025-08-21 DOI: 10.1038/s41408-025-01344-3
Jules Higué, Corentin Orvain, Pierre-Yves Dumas, Pierre Peterlin, Marie-Anne Hospital, Sabrina Barrière, Audrey Couturier, Martin Carre, Areti Chantzi, Emmanuelle Tavernier, Éric Delabesse, Audrey Bidet, Anne Bouvier, Marie-Joelle Mozziconacci, Lauren Véronèse, Cédric Pastoret, Sylvie Tondeur, Pascale Flandrin-Gresta, Sébastien Lachot, Marine Cazaux, Sylvain Thépot, Edouard Forcade, Patrice Chevallier, Raynier Devillier, Gaspar Aspas Requena, Sarah Bertoli, Arnaud Pigneux, Christian Récher
{"title":"Venetoclax and azacitidine for molecular relapse after intensive chemotherapy in NPM1 or CBF AML: a FILO study","authors":"Jules Higué, Corentin Orvain, Pierre-Yves Dumas, Pierre Peterlin, Marie-Anne Hospital, Sabrina Barrière, Audrey Couturier, Martin Carre, Areti Chantzi, Emmanuelle Tavernier, Éric Delabesse, Audrey Bidet, Anne Bouvier, Marie-Joelle Mozziconacci, Lauren Véronèse, Cédric Pastoret, Sylvie Tondeur, Pascale Flandrin-Gresta, Sébastien Lachot, Marine Cazaux, Sylvain Thépot, Edouard Forcade, Patrice Chevallier, Raynier Devillier, Gaspar Aspas Requena, Sarah Bertoli, Arnaud Pigneux, Christian Récher","doi":"10.1038/s41408-025-01344-3","DOIUrl":"https://doi.org/10.1038/s41408-025-01344-3","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"12 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899269","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}
引用次数: 0
Assessing the performance of the Iceland screens, treats, or prevents multiple myeloma (iStopMM) model in a multicultural Bronx cohort: implications for monoclonal gammopathy of undetermined significance risk stratification 在多文化布朗克斯队列中评估冰岛筛查、治疗或预防多发性骨髓瘤(iStopMM)模型的性能:对未确定显著性风险分层的单克隆γ病的影响
IF 12.8 1区 医学
Blood Cancer Journal Pub Date : 2025-08-21 DOI: 10.1038/s41408-025-01337-2
Rajvi Gor, Jeevan Shivakumar, Pallavi Surana, John Wei, Irina Murakhovskaya, Mendel Goldfinger, Noah Kornblum, Lauren Shapiro, Aditi Shastri, Ridhi Gupta, David Levitz, Marina Konopleva, Eric Feldman, Kira Gritsman, R. Alejandro Sica, Ioannis Mantzaris, Amit Verma, Dennis Cooper, Murali Janakiram, Nishi Shah
{"title":"Assessing the performance of the Iceland screens, treats, or prevents multiple myeloma (iStopMM) model in a multicultural Bronx cohort: implications for monoclonal gammopathy of undetermined significance risk stratification","authors":"Rajvi Gor, Jeevan Shivakumar, Pallavi Surana, John Wei, Irina Murakhovskaya, Mendel Goldfinger, Noah Kornblum, Lauren Shapiro, Aditi Shastri, Ridhi Gupta, David Levitz, Marina Konopleva, Eric Feldman, Kira Gritsman, R. Alejandro Sica, Ioannis Mantzaris, Amit Verma, Dennis Cooper, Murali Janakiram, Nishi Shah","doi":"10.1038/s41408-025-01337-2","DOIUrl":"https://doi.org/10.1038/s41408-025-01337-2","url":null,"abstract":"<p>The Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) risk stratification model, developed to predict ≥10% abnormal plasma cells in the bone marrow in monoclonal gammopathy of undetermined significance (MGUS) patients, was developed in a predominantly White and genetically homogeneous Icelandic population, lacking external validation. Our study aimed to externally validate this model in a racially and ethnically diverse Bronx population. The medical records of patients at Montefiore Medical Center (2002–2023) were searched to identify patients with MGUS who had undergone a bone marrow biopsy. For each patient, the iStopMM variables were entered into the iStopMM prediction model, and predicted, and actual plasma cell percentages were recorded. The area under the receiver operating characteristic (AUROC) curve assessed the iStopMM model’s performance in predicting ≥10% plasma cells, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Of the initial 663 patients, 190 were included in the final cohort, of whom 52.6% were African-Americans, and 23.2% identified themselves as Hispanic/Latino, remarkably different from the homogenous population of the iStopMM study. The iStopMM predictive model was able to predict greater than or equal to 10% plasma cells on bone marrow biopsy with an AUROC of 0.78 (CI 0.71, 0.85). When set at a 10% threshold for predicting SMM or worse, the iStopMM model had a 93.3% sensitivity, 33.7% specificity, 55.3% PPV, and 85.0% NPV. This AUROC value of 0.778 suggests a reasonable discriminatory performance of the model in our racially and ethnically diverse Bronx population.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"52 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899313","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}
引用次数: 0
Newly diagnosed acute myeloid leukemia in unfit patients: 2026 treatment algorithms 新诊断急性髓系白血病不适合患者:2026治疗算法
IF 12.8 1区 医学
Blood Cancer Journal Pub Date : 2025-08-16 DOI: 10.1038/s41408-025-01346-1
Naseema Gangat, Courtney D. Dinardo
{"title":"Newly diagnosed acute myeloid leukemia in unfit patients: 2026 treatment algorithms","authors":"Naseema Gangat, Courtney D. Dinardo","doi":"10.1038/s41408-025-01346-1","DOIUrl":"https://doi.org/10.1038/s41408-025-01346-1","url":null,"abstract":"<p>Management paradigms for newly-diagnosed acute myeloid leukemia (ND-AML) in patients considered <i>unfit</i> to receive intensive chemotherapy have evolved with improved understanding of disease biology. In this setting, management requires clear delineation of goals of therapy that should include preservation of quality-of-life (QoL). Combination of venetoclax (Ven) and a hypomethylating agent (HMA) is the current standard-of-care in most circumstances with flexible options in regard to drug dose and duration of treatment as well as the addition (triplet combinations) or alternative use of targeted therapies, such as inhibitors of <i>FLT3</i>, <i>IDH1</i>, <i>IDH2</i>, or menin for patients with <i>NPM1</i><sup>MUT</sup> or <i>KMT2A</i> rearrangements (<i>KMT2Ar</i>). Response rates (CR/CRi:40-90%) and overall survival outcomes (3-year: 0–67%) following Ven-HMA therapy are highly variable and depend primarily on tumor genetics while achievement of complete response with (CR) or without count recovery (CRi) and consolidation with allogeneic stem cell transplant (ASCT) are essential in securing long-term survival. <i>Favorable</i> genomic predictors of response to Ven-HMA include <i>NPM1</i><sup>MUT</sup>, <i>IDH2</i><sup>MUT</sup>, and <i>DDX41</i><sup>MUT</sup>, and <i>unfavorable TP53</i><sup>MUT</sup>, <i>FLT3-</i>ITD, and <i>K/NRAS</i><sup>MUT</sup>. <i>Favorable</i> predictors of overall survival include <i>IDH2</i><sup>MUT</sup>, and <i>unfavorable TP53</i><sup>MUT</sup>, <i>FLT3-</i>ITD, <i>K/NRAS</i><sup>MUT</sup>, and <i>KMT2Ar</i>. Whether or not triplet regimens provide significant survival gain over Ven-HMA in genetically targetable subgroups remains to be determined. Particularly frail patients who are considered <i>unfit</i> for Ven-HMA might benefit from monotherapy targeting <i>FLT3</i><sup>MUT</sup>, <i>IDH1/2</i><sup>MUT</sup>, <i>NPM1</i><sup>MUT</sup>or <i>KMT2Ar</i>. Future research projects should focus on incorporating patient-reported outcomes in clinical trials, optimization of Ven-HMA dosing and treatment duration especially in triplet combinations and broadening the use of ASCT and clarification of its timing.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"7 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860108","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}
引用次数: 0
Clinical and molecular characterization of TP53-mutant acute lymphoblastic leukemia in adults 成人tp53突变急性淋巴细胞白血病的临床和分子特征
IF 12.8 1区 医学
Blood Cancer Journal Pub Date : 2025-08-14 DOI: 10.1038/s41408-025-01350-5
Ethan J. Harris, Diren Arda Karaoglu, Madina Sukhanova, Yasmin Abaza, Theodoros Karantanos, Ann-Kathrin Eisfeld, Clare Anderson, Chenyu Lin, Yenny A. Moreno Vanegas, Talha Badar, Alexander Coltoff, Todd C. Knepper, Neval Ozkaya, Hamed Rahmani Youshanlouei, Sinan Cetin, Anand A. Patel, Adam S. DuVall, Michael W. Drazer, Peng Wang, Melissa Tjota, Jeremy P. Segal, Girish Venkataraman, Sandeep Gurbuxani, Jason X. Cheng, Daniel A. Arber, Richard A. Larson, Olatoyosi Odenike, Jonathan Webster, Bijal Shah, Wendy Stock, Caner Saygin
{"title":"Clinical and molecular characterization of TP53-mutant acute lymphoblastic leukemia in adults","authors":"Ethan J. Harris, Diren Arda Karaoglu, Madina Sukhanova, Yasmin Abaza, Theodoros Karantanos, Ann-Kathrin Eisfeld, Clare Anderson, Chenyu Lin, Yenny A. Moreno Vanegas, Talha Badar, Alexander Coltoff, Todd C. Knepper, Neval Ozkaya, Hamed Rahmani Youshanlouei, Sinan Cetin, Anand A. Patel, Adam S. DuVall, Michael W. Drazer, Peng Wang, Melissa Tjota, Jeremy P. Segal, Girish Venkataraman, Sandeep Gurbuxani, Jason X. Cheng, Daniel A. Arber, Richard A. Larson, Olatoyosi Odenike, Jonathan Webster, Bijal Shah, Wendy Stock, Caner Saygin","doi":"10.1038/s41408-025-01350-5","DOIUrl":"https://doi.org/10.1038/s41408-025-01350-5","url":null,"abstract":"<p><i>TP53</i>-mutant acute lymphoblastic leukemia (ALL) in adults is a high-risk subtype with poor outcomes, yet its molecular landscape and clinical implications remain incompletely defined. In this multi-institutional study of 830 adult ALL patients treated at eight academic centers between 2010 and 2024, we demonstrated that <i>TP53</i> mutations are independent predictors of inferior overall survival in both B-ALL (median, 1.9 vs 5 years) and T-ALL (1.6 vs 9.5 years), irrespective of age, biologic disease subtype, or therapy. Genomic profiling revealed that &gt;90% of <i>TP53</i> mutations were DNA-binding domain missense variants, frequently co-occurring with hypodiploidy in B-ALL and NOTCH1/FBXW7 mutations in T-ALL. Unlike myeloid malignancies, biallelic <i>TP53</i> mutations did not worsen outcomes, and variant type (missense vs truncating) did not influence survival. <i>TP53</i>-mutant B-ALL exhibited higher CD20 positivity than <i>TP53-</i>wild type B-ALL (65% vs 31%) but had inferior responses to conventional chemotherapy. Novel immunotherapies (e.g., inotuzumab/blinatumomab) or venetoclax-containing combination regimens improved remission rates, yet relapses were common, often with CD19/CD20/CD22 loss (triple-negative) or acquisition of new mutations. Allogeneic transplantation in first remission trended toward survival benefit (median, 3.3 vs 2.2 years). These findings underscore <i>TP53</i>-mutant ALL as a distinct, chemo-resistant entity necessitating tailored approaches, with antigen escape highlighting challenges of immunotherapy durability.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"86 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851442","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}
引用次数: 0
Impact of daratumumab refractoriness on clinical outcomes following CAR T-cell therapy for relapsed refractory multiple myeloma daratumumab的难治性对CAR - t细胞治疗复发难治性多发性骨髓瘤后临床结果的影响
IF 12.8 1区 医学
Blood Cancer Journal Pub Date : 2025-08-14 DOI: 10.1038/s41408-025-01343-4
T. Sebastian, S. Rajeeve, T. Farzana, R. Firestone, E. Jurgens, K. Miller, B. Costa, A. Lesokhin, C. Tan, G. Shah, N. Korde, H. Landau, M. Scordo, H. Hassoun, K. Maclachlan, U. Shah, M. Hultcrantz, A. Derkach, D. Nemirovsky, S. Giralt, S. Z. Usmani, S. Mailankody, H. Hashmi
{"title":"Impact of daratumumab refractoriness on clinical outcomes following CAR T-cell therapy for relapsed refractory multiple myeloma","authors":"T. Sebastian, S. Rajeeve, T. Farzana, R. Firestone, E. Jurgens, K. Miller, B. Costa, A. Lesokhin, C. Tan, G. Shah, N. Korde, H. Landau, M. Scordo, H. Hassoun, K. Maclachlan, U. Shah, M. Hultcrantz, A. Derkach, D. Nemirovsky, S. Giralt, S. Z. Usmani, S. Mailankody, H. Hashmi","doi":"10.1038/s41408-025-01343-4","DOIUrl":"https://doi.org/10.1038/s41408-025-01343-4","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"146 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851381","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}
引用次数: 0
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