Haematologica最新文献

{"title":"AURKA targeting: a NEAT approach to halt myeloma.","authors":"Antonio Giovanni Solimando, Cirino Botta","doi":"10.3324/haematol.2024.286085","DOIUrl":"10.3324/haematol.2024.286085","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3847-3849"},"PeriodicalIF":8.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106889","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}

{"title":"Clinical impact of clonal hematopoiesis in hematopoietic cell transplantation: a review, meta-analysis, and call to action.","authors":"Nancy Gillis, Amr Ebied, Zachary J Thompson, Joseph A Pidala","doi":"10.3324/haematol.2024.285392","DOIUrl":"10.3324/haematol.2024.285392","url":null,"abstract":"<p><p>Hematopoietic cell transplantation (HCT) is the only potentially curative treatment option for many patients with hematologic malignancies. While HCT outcomes have improved drastically over the years, patients and clinicians continue to face numerous survivorship challenges, such as relapse, graft-versus-host disease, and secondary malignancies. Recent literature suggests that clonal hematopoiesis (CH), the presence of a recurrent somatic mutation in hematopoietic cells, in HCT patients or donors may be associated with outcomes in autologous and allogeneic HCT. Herein, we perform a review of the literature and summarize reported associations between CH and clinical outcomes in HCT. For commonly reported outcomes, we used meta-analysis methods to provide estimates of effect sizes when combining results. A total of 32 articles with relevant and independent contributions were included, covering both autologous (N=19) and allogeneic (N=13) HCT. The articles report variable risk for developing outcomes according to CH characteristics, patient disease status, and method of HCT. Using meta-analysis of available results, HCT outcomes with statistically significant effects by CH status include therapy-related myeloid neoplasms (odds ratio =3.65; 95% confidence interval [CI]: 2.18-6.10) and overall survival (hazard ratio [HR]=1.38; 95% CI: 1.20-1.58) in autologous HCT and relapse (HR=0.80; 95% CI: 0.68-0.94) in allogeneic HCT. However, heterogeneity, biases, and limitations in the literature provide challenges for informing the translation of CH to clinical decision- making. We conclude with a call to action and discussion of next steps to build upon the current literature and provide granularity to the true clinical impact of CH in the setting of HCT.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3952-3964"},"PeriodicalIF":8.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426733","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}

{"title":"Umbilical cord blood T cells can be isolated and enriched by CD62L selection for use in 'off the shelf' chimeric antigen receptor T-cell therapies to widen transplant options.","authors":"Christos Georgiadis, Lauren Nickolay, Farhatullah Syed, Hong Zhan, Soragia Athina Gkazi, Annie Etuk, Ulrike Abramowski-Mock, Roland Preece, Piotr Cuber, Stuart Adams, Giorgio Ottaviano, Waseem Qasim","doi":"10.3324/haematol.2024.285101","DOIUrl":"10.3324/haematol.2024.285101","url":null,"abstract":"<p><p>Umbilical cord blood (UCB) T cells exhibit distinct naïve ontogenetic profiles and may be an attractive source of starting cells for the production of chimeric antigen receptor (CAR) T cells. Pre-selection of UCB-T cells on the basis of CD62L expression was investigated as part of a machine-based manufacturing process, incorporating lentiviral transduction, CRISPR- Cas9 editing, T-cell expansion, and depletion of residual TCRαβ T cells. This provided stringent mitigation against the risk of graft-versus-host disease (GvHD), and was combined with simultaneous knockout of CD52 to enable persistence of edited T cells in combination with preparative lymphodepletion using alemtuzumab. Under compliant manufacturing conditions, two cell banks were generated with high levels of CAR19 expression and minimal carriage of TCRαβ T cells. Sufficient cells were cryopreserved in dose-banded aliquots at the end of each campaign to treat dozens of potential recipients. Molecular characterization captured vector integration sites and CRISPR editing signatures, and functional studies, including in vivo potency studies in humanized mice, confirmed anti-leukemic activity comparable to peripheral blood-derived universal CAR19 T cells. Machine manufactured UCB-derived T-cell banks offer an alternative to autologous cell therapies and could help widen access to CAR T cells.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3941-3951"},"PeriodicalIF":8.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579545","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}

{"title":"Expanding the genetic landscape of congenital neutropenia: <i>CXCR2</i> mutations in three families revealed through whole exome sequencing.","authors":"Maksim Klimiankou, Ivan Tesakov, Grigorios Tsaknakis, Erasmia Boutakoglou, Irene Mavroudi, Malte Ritter, Marc Sturm, Julia Skokowa, Helen A Papadaki","doi":"10.3324/haematol.2024.285569","DOIUrl":"10.3324/haematol.2024.285569","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"4140-4144"},"PeriodicalIF":8.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859560","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}

{"title":"Superior survival with allogeneic hematopoietic stem cell transplantation <i>versus</i> chemotherapy for high-risk adult acute lymphoblastic leukemia in a PDT-ALL-2016 pediatric-inspired cohort.","authors":"Junjie Chen, Zihong Cai, Zicong Huang, Jieping Lin, Zhixiang Wang, Jiawang Ou, Xiuli Xu, Bingqing Tang, Chenhao Ding, Jia Li, Ren Lin, Ting Zhang, Li Xuan, Qifa Liu, Hongsheng Zhou","doi":"10.3324/haematol.2024.285590","DOIUrl":"10.3324/haematol.2024.285590","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"4125-4130"},"PeriodicalIF":8.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859564","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}

{"title":"Entities <i>versus</i> diseases: Myers <i>et al.</i> propose distinct aspects of adult T-cell lymphoma/leukemia.","authors":"Stefano A Pileri","doi":"10.3324/haematol.2024.286174","DOIUrl":"10.3324/haematol.2024.286174","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3844-3846"},"PeriodicalIF":8.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106892","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}

{"title":"Minor trauma and venous thromboembolism: the threshold for antithrombotic prophylaxis.","authors":"Alexandre Tran, Pamela L Lutsey, Marc Carrier","doi":"10.3324/haematol.2023.284612","DOIUrl":"https://doi.org/10.3324/haematol.2023.284612","url":null,"abstract":"<p><p>Trauma is an established risk factor for venous thromboembolism (VTE). Whether minor trauma is linked to greater risk of VTE remains unclear given that many studies evaluating trauma and VTE risk have not differentiated risk by trauma severity. Furthermore, the underlying risk of VTE is not uniform across all injured patients. While it is generally accepted that severely and moderately injured patients requiring prolonged hospitalization benefit from early and consistent administration of thromboprophylaxis, the threshold for its initiation following minor injury or in patients managed in an ambulatory setting is less clear. This review will describe how trauma is classified, summarize the evidence of the risk of VTE in patients with minor trauma, and guide clinicians through an approach to individualize these treatment decisions based on contemporary evidence. Guidance will be provided for both injured patients requiring hospitalization (who may have severe, moderate or minor trauma), and those suitable to be managed in an ambulatory setting (minor trauma).</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"109 12","pages":"3860-3867"},"PeriodicalIF":8.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768540","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}

{"title":"Safety and efficacy of flumatinib as later-line therapy in patients with chronic myeloid leukemia.","authors":"Yunfan Yang, Yuntao Liu, Hui Sun, Li Meng, Hai Lin, Chunyan Chen, Jianda Hu, Xuliang Shen, Minghui Duan, Yanli Zhang, Dilinazi Abulaiti, Jinghua Wang, Hongqian Zhu, Luoming Hua, Qing Leng, Chun Zhang, Lili Sun, Weiming Li, Huanling Zhu, Bingcheng Liu, Jianxiang Wang","doi":"10.3324/haematol.2023.284892","DOIUrl":"10.3324/haematol.2023.284892","url":null,"abstract":"<p><p>The aim of this study was to evaluate the efficacy and safety of flumatinib in later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia ((CP-CML) previously treated with tyrosine kinase inhibitors (TKI). Patients with CML-CP were evaluated for probabilities of responses, including complete hematologic response (CHR), cytogenetic response, and molecular response (MR), and adverse events after the later-line flumatinib therapy. Of 336 enrolled patients with a median age 50 years, the median duration of treatment with flumatinib was 11.04 months (range, 2-25.23). Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR) or 2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% of patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR were achieved in 86.4%, 52.7%, 49.6%, and 23.5% of patients, respectively, who lacked the respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as a second-line TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR rates. The adverse events observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who were resistant or intolerant to other TKI. In particular, second-line flumatinib treatment induced high response rates and was more beneficial to patients without previous second-generation TKI resistance, thus serving as a probable treatment option for these patients.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3965-3974"},"PeriodicalIF":8.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456374","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}

{"title":"LSD1/KDM1A and GFI1B repress endothelial fate and induce hematopoietic fate in induced pluripotent stem cell-derived hemogenic endothelium.","authors":"Huan Zhang, Marten Hansen, Franca Di Summa, Marieke Von Lindern, Nynke Gillemans, Wilfred F J Van IJcken, Arthur Flohr Svendsen, Sjaak Philipsen, Bert Van der Reijden, Eszter Varga, Emile Van den Akker","doi":"10.3324/haematol.2024.285214","DOIUrl":"10.3324/haematol.2024.285214","url":null,"abstract":"<p><p>Differentiation of induced pluripotent stem cells (iPSC) into hematopoietic lineages offers great therapeutic potential. During embryogenesis, hemogenic endothelium (HE) gives rise to hematopoietic stem and progenitor cells through the endothelial- to-hematopoietic transition (EHT). Understanding this process using iPSC is key to generating functional hematopoietic stem cells (HSC), a currently unmet challenge. In this study, we examined the role of the transcriptional factor GFI1B and its co-factor LSD1/KDM1A in EHT. To this end, we employed patient-derived iPSC lines with a dominant-negative dysfunctional GFI1B Q287* and irreversible pharmacological LSD1/KDM1A inhibition in healthy iPSC lines. The formation of HE remained unaffected; however, hematopoietic output was severely reduced in both conditions. Single-cell RNA sequencing (scRNAseq) performed on the CD144+/CD31+ population derived from healthy iPSC revealed similar expression dynamics of genes associated with in vivo EHT. Interestingly, LSD1/KDM1A inhibition in healthy lines before EHT resulted in a complete absence of hematopoietic output. However, uncommitted HE cells did not display GFI1B expression, suggesting a timed transcriptional program. To test this hypothesis, we ectopically expressed GFI1B in uncommitted HE cells, leading to downregulation of endothelial genes and upregulation of hematopoietic genes, including GATA2, KIT, RUNX1, and SPI1. Thus, we demonstrate that LSD1/KDM1A and GFI1B can function at distinct temporal points in different cellular subsets during EHT. Although GFI1B is not detected in uncommitted HE cells, its ectopic expression allows for partial hematopoietic specification. These data indicate that precisely timed expression of specific transcriptional regulators during EHT is crucial to the eventual outcome of EHT.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3975-3988"},"PeriodicalIF":8.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497898","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}

{"title":"A new frontier in the battle against infant acute lymphoblastic leukemia.","authors":"Daisuke Tomizawa","doi":"10.3324/haematol.2024.285975","DOIUrl":"10.3324/haematol.2024.285975","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3838-3840"},"PeriodicalIF":8.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633286","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}