LeukemiaPub Date : 2024-12-12DOI: 10.1038/s41375-024-02497-z
Corentin Orvain, Filippo Milano, Eduardo Rodríguez-Arbolí, Megan Othus, Effie W. Petersdorf, Brenda M. Sandmaier, Frederick R. Appelbaum, Roland B. Walter
{"title":"Relationship between donor source, pre-transplant measurable residual disease, and outcome after allografting for adults with acute myeloid leukemia","authors":"Corentin Orvain, Filippo Milano, Eduardo Rodríguez-Arbolí, Megan Othus, Effie W. Petersdorf, Brenda M. Sandmaier, Frederick R. Appelbaum, Roland B. Walter","doi":"10.1038/s41375-024-02497-z","DOIUrl":"10.1038/s41375-024-02497-z","url":null,"abstract":"Lack of HLA-matched related/unrelated donor remains a barrier to allogeneic hematopoietic cell transplantation (HCT) for adult acute myeloid leukemia (AML), with ongoing uncertainty about optimal donor type if more than one alternative donor is available. To assess the relationship between donor type, pre-HCT measurable residual disease (MRD), and post-HCT outcomes, we retrospectively analyzed 1265 myelodysplastic neoplasm (MDS)/AML and AML patients allografted in first or second remission with an HLA-matched sibling (MSD) or unrelated donor (MUD), HLA-mismatched unrelated donor (MMD), an HLA-haploidentical donor, or umbilical cord blood (UCB) at a single institution. Relapse risk was non-significantly higher after HLA-haploidentical and lower after UCB HCT. Non-relapse mortality (NRM) was significantly higher in patients undergoing MMD HCT, HLA-haploidentical HCT, and UCB, translating into significantly lower relapse-free survival (RFS) and overall survival for MMD and HLA-haploidentical HCT. There was a significant interaction between conditioning intensity and post-HCT outcomes for UCB HCT with better RFS for UCB HCT after MAC but higher NRM after non-MAC. In patients with pre-HCT MRD receiving MAC, relapse risk was significantly lower and RFS higher in those who underwent UCB HCT in comparison to MSD/MUD. Together, UCB HCT is a valuable alternative for MAC HCT, particularly in patients with pre-HCT MRD.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"381-390"},"PeriodicalIF":12.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02497-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815781","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}
LeukemiaPub Date : 2024-12-12DOI: 10.1038/s41375-024-02470-w
Mylène Gerritsen, Florentien E. M. in ’t Hout, Ruth Knops, Bas L. R. Mandos, Melanie Decker, Tim Ripperger, Bert A. van der Reijden, Joost H. A. Martens, Joop H. Jansen
{"title":"Acute myeloid leukemia associated RUNX1 variants induce aberrant expression of transcription factor TCF4","authors":"Mylène Gerritsen, Florentien E. M. in ’t Hout, Ruth Knops, Bas L. R. Mandos, Melanie Decker, Tim Ripperger, Bert A. van der Reijden, Joost H. A. Martens, Joop H. Jansen","doi":"10.1038/s41375-024-02470-w","DOIUrl":"10.1038/s41375-024-02470-w","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"520-523"},"PeriodicalIF":12.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809620","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}
LeukemiaPub Date : 2024-12-11DOI: 10.1038/s41375-024-02474-6
Eleni A. Argyriadi, Ingo G. Steffen, Christiane Chen-Santel, Andrej Lissat, Andishe Attarbaschi, Jean-Pierre Bourquin, Guenter Henze, Arend von Stackelberg
{"title":"Prognostic relevance of treatment deviations in children with relapsed acute lymphoblastic leukemia who were treated in the ALL-REZ BFM 2002 study","authors":"Eleni A. Argyriadi, Ingo G. Steffen, Christiane Chen-Santel, Andrej Lissat, Andishe Attarbaschi, Jean-Pierre Bourquin, Guenter Henze, Arend von Stackelberg","doi":"10.1038/s41375-024-02474-6","DOIUrl":"10.1038/s41375-024-02474-6","url":null,"abstract":"Relapsed Acute Lymphoblastic Leukemia (ALL) is among the most common causes of cancer-associated deaths in children. However, little is known about the implications of deviations from ALL treatment protocols on survival rates. The present study elucidates the various characteristics of treatment deviations in children with relapsed ALL included in the ALL-REZ BFM 2002 (i.e., Relapse Berlin-Frankfurt- Münster) trial and determines their prognostic relevance for relapse and death rates. Among 687 patients, 100 were identified with treatment deviations, further classified, and examined by occurrence time, cause and type. Protocol deviation was considered a time-dependent variable and its impact on Disease Free Survival (DFS) and Overall Survival (OS) was examined using the time-dependent model Mantel Byar. Five years after the relapse diagnosis, deviations were significantly related to both inferior DFS (38%) and OS (57%) rates compared to protocol conformed treatment (DFS = 61%; OS = 70%, P < 0.001). Based on multivariate analyses, protocol deviation proved to be an independent adverse prognostic factor of DFS. Moreover, deviations triggered by chemotherapy-induced toxicity were associated with a higher relapse rate compared to deviations due to insufficient response. Therefore, to avoid impairment of results by deviations, future clinical trials, and treatment strategies should focus on less toxic treatments and stricter protocol compliance.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"337-345"},"PeriodicalIF":12.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02474-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809726","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}
LeukemiaPub Date : 2024-12-10DOI: 10.1038/s41375-024-02483-5
Florian Simon, Othman Al-Sawaf, John F. Seymour, Barbara Eichhorst
{"title":"Surrogate endpoints in mature B-cell neoplasms – meaningful or misleading?","authors":"Florian Simon, Othman Al-Sawaf, John F. Seymour, Barbara Eichhorst","doi":"10.1038/s41375-024-02483-5","DOIUrl":"10.1038/s41375-024-02483-5","url":null,"abstract":"Indolent mature B-cell neoplasms are a group of diseases in which recent therapeutic advances have led to an improved overall survival (OS) extending beyond several years. While cause of celebration for patients and caregivers, the increasingly long observation periods necessary to capture treatment effects are complicating trial design and possibly hindering swift access to more effective therapies. Surrogate endpoints are a tool with the potential of earlier study readouts, however, their validity needs to be proven in each individual disease and therapeutic setting. The validation of surrogate endpoints and available data for mature B-cell neoplasms are discussed within this perspective article, followed by an outlook on the potential of precise tools such as measurable residual disease assessment as novel surrogate candidates.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"25-28"},"PeriodicalIF":12.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02483-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796999","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}
LeukemiaPub Date : 2024-12-10DOI: 10.1038/s41375-024-02492-4
Paul J. Hampel, Kari G. Rabe, Yucai Wang, Steven R. Hwang, Saad S. Kenderian, Eli Muchtar, Jose F. Leis, Amber B. Koehler, Mazie Tsang, Talal Hilal, Ricardo Parrondo, Rachel J. Bailen, Susan M. Schwager, Curtis A. Hanson, Esteban Braggio, Susan L. Slager, Min Shi, Cinthya J. Zepeda-Mendoza, Daniel L. Van Dyke, Tait D. Shanafelt, Rebecca L. King, Timothy G. Call, Neil E. Kay, Wei Ding, Sameer A. Parikh
{"title":"Incidence of Richter transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma in the targeted therapy era","authors":"Paul J. Hampel, Kari G. Rabe, Yucai Wang, Steven R. Hwang, Saad S. Kenderian, Eli Muchtar, Jose F. Leis, Amber B. Koehler, Mazie Tsang, Talal Hilal, Ricardo Parrondo, Rachel J. Bailen, Susan M. Schwager, Curtis A. Hanson, Esteban Braggio, Susan L. Slager, Min Shi, Cinthya J. Zepeda-Mendoza, Daniel L. Van Dyke, Tait D. Shanafelt, Rebecca L. King, Timothy G. Call, Neil E. Kay, Wei Ding, Sameer A. Parikh","doi":"10.1038/s41375-024-02492-4","DOIUrl":"10.1038/s41375-024-02492-4","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"503-507"},"PeriodicalIF":12.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796997","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}
LeukemiaPub Date : 2024-12-04DOI: 10.1038/s41375-024-02486-2
Sen Yang, Xiaoshuai Zhang, Robert Peter Gale, Xiaojun Huang, Qian Jiang
{"title":"Is there really an accelerated phase of chronic myeloid leukaemia at presentation?","authors":"Sen Yang, Xiaoshuai Zhang, Robert Peter Gale, Xiaojun Huang, Qian Jiang","doi":"10.1038/s41375-024-02486-2","DOIUrl":"10.1038/s41375-024-02486-2","url":null,"abstract":"Whether there is really a distinct accelerated phase (AP) at diagnosis in chronic myeloid leukaemia (CML) in the context of tyrosine kinase-inhibitor (TKI)-therapy is controversial. We studied 2122 consecutive subjects in chronic phase (CP, n = 1837) or AP (n = 285) at diagnosis classified according to the 2020 European LeukemiaNet (ELN) classification. AP subjects with increased basophils only had similar transformation-free survival (TFS) and survival compared with CP subjects classified as ELTS intermediate-risk. Those with increased blasts only had worse TFS but similar survival compared with CP subjects classified as ELTS high-risk. AP subjects with decreased platelets only had similar TFS but worse survival compared with subjects classified as ELTS high-risk. Proportions of CP and AP subjects meeting the 2020 ELN TKI-response milestones were similar. However, worse TFS at 3-month and survival at 6- or 12-month were only in AP subjects failing to meet ELN milestones. Findings were similar using the 2022 International Consensus Classification (ICC) criteria for AP replacing decreased platelets with additional cytogenetic abnormalities. Our data support the 2022 WHO classification of CML eliminating AP. We suggest adding a very high-risk cohort to the ELTS score including people with increased blasts or decreased platelets and dividing CML into 2 phases at diagnosis: CP and acute or blast phases.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"391-399"},"PeriodicalIF":12.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02486-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763190","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}
LeukemiaPub Date : 2024-12-04DOI: 10.1038/s41375-024-02485-3
Saioa Arza-Apalategi, Branco M. H. Heuts, Saskia M. Bergevoet, Roos Meering, Daan Gilissen, Pascal W. T. C. Jansen, Anja Krippner-Heidenreich, Peter J. M. Valk, Michiel Vermeulen, Olaf Heidenreich, Torsten Haferlach, Joop H. Jansen, Joost H. A. Martens, Bert A. van der Reijden
{"title":"HMX3 is a critical vulnerability in MECOM-negative KMT2A::MLLT3 acute myelomonocytic leukemia","authors":"Saioa Arza-Apalategi, Branco M. H. Heuts, Saskia M. Bergevoet, Roos Meering, Daan Gilissen, Pascal W. T. C. Jansen, Anja Krippner-Heidenreich, Peter J. M. Valk, Michiel Vermeulen, Olaf Heidenreich, Torsten Haferlach, Joop H. Jansen, Joost H. A. Martens, Bert A. van der Reijden","doi":"10.1038/s41375-024-02485-3","DOIUrl":"10.1038/s41375-024-02485-3","url":null,"abstract":"KMT2A::MLLT3 acute myelomonocytic leukemia (AML) comes in two clinically and biologically different subtypes. One is characterized by inferior outcome, older age, and MECOM oncogene expression. The other is mainly observed in children and young adults, associates with better clinical outcome, but lacks MECOM. To identify cell fate determining transcription factors downstream of KMT2A::MLLT3, we applied a bioinformatic algorithm that integrates gene and enhancer expression from primary MECOM-positive and -negative KMT2A::MLLT3 AML samples. This identified MECOM to be most influential in the MECOM-positive group, while neuronal transcription factor HMX3 was most influential in the MECOM-negative group. In large AML cohorts, HMX3 expression associated with a unique gene expression profile, younger age (p < 0.002) and KMT2A-rearranged and KAT6A-CREBBP leukemia (p < 0.00001). HMX3 was not expressed in other major genetic risk groups and healthy blood cells. RNA-sequencing analyses following forced HMX3 expression in healthy CD34+ cells and its silencing in KMT2A::MLT3 cells showed that HMX3 drives cancer-associated E2F and MYC gene programs (p < 0.001). HMX3 expression in healthy CD34+ cells blocked monocytic but not granulocytic colony formation. Strikingly, HMX3 silencing in KMT2A::MLLT3 patient cells resulted in cell cycle arrest, monocytic differentiation and apoptosis. Thus, the neuronal transcription factor HMX3 is a leukemia-specific vulnerability in KMT2A::MLLT3 AML.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"371-380"},"PeriodicalIF":12.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763191","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}
LeukemiaPub Date : 2024-12-03DOI: 10.1038/s41375-024-02487-1
Jeff P. Sharman, Miklos Egyed, Wojciech Jurczak, Alan Skarbnik, John M. Pagel, Ian W. Flinn, Manali Kamdar, Talha Munir, Renata Walewska, Gillian Corbett, Laura Maria Fogliatto, Yair Herishanu, Versha Banerji, Steven Coutre, George Follows, Patricia Walker, Karin Karlsson, Paolo Ghia, Ann Janssens, Florence Cymbalista, Jennifer A. Woyach, Emmanuelle Ferrant, William G. Wierda, Veerendra Munugalavadla, Ting Yu, Min Hui Wang, John C. Byrd
{"title":"Correction: Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naïve chronic lymphocytic leukemia","authors":"Jeff P. Sharman, Miklos Egyed, Wojciech Jurczak, Alan Skarbnik, John M. Pagel, Ian W. Flinn, Manali Kamdar, Talha Munir, Renata Walewska, Gillian Corbett, Laura Maria Fogliatto, Yair Herishanu, Versha Banerji, Steven Coutre, George Follows, Patricia Walker, Karin Karlsson, Paolo Ghia, Ann Janssens, Florence Cymbalista, Jennifer A. Woyach, Emmanuelle Ferrant, William G. Wierda, Veerendra Munugalavadla, Ting Yu, Min Hui Wang, John C. Byrd","doi":"10.1038/s41375-024-02487-1","DOIUrl":"10.1038/s41375-024-02487-1","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"529-529"},"PeriodicalIF":12.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02487-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770615","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}
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