Hematological Oncology最新文献

{"title":"Antibody targeting of surface P-selectin glycoprotein ligand 1 leads to lymphoma apoptosis and tumorigenesis inhibition","authors":"João L. Pereira,&nbsp;Francisca Ferreira,&nbsp;Nuno R. dos Santos","doi":"10.1002/hon.3257","DOIUrl":"10.1002/hon.3257","url":null,"abstract":"<p>Lymphomas are a heterogeneous group of diseases that originate from T, B or natural killer cells. Lymphoma treatment is based on chemotherapy, radiotherapy, and monoclonal antibody (mAb) or other immunotherapies. The P-selectin glycoprotein ligand 1 (PSGL-1) is expressed at the surface of hematological malignant cells and has been shown to have a pro-oncogenic role in multiple myeloma and lymphoma. Here, we investigated the expression and therapeutic potential of PSGL-1 in T and B cell lymphomas. By flow cytometry analysis, we found that PSGL-1 was expressed in both T and B cell-derived lymphoma cell lines but generally at higher levels in T cell lymphoma cell lines. For most T and B cell-derived lymphoma cell lines, in vitro targeting with the PL1 mAb, which recognizes the PSGL-1 N-terminal extracellular region and blocks functional interactions with selectins, resulted in reduced cell viability. The PL1 mAb pro-apoptotic activity was shown to be dose-dependent, to be linked to increased ERK kinase phosphorylation, and to be dependent on the MAP kinase signaling pathway. Importantly, anti-PSGL-1 treatment of mice xenografted with the HUT-78 cutaneous T-cell lymphoma cell line resulted in decreased tumor growth, had no effect on in vivo proliferation, but increased the levels of apoptosis in tumors. Anti-PSGL-1 treatment of mice xenografted with a Burkitt lymphoma cell line that was resistant to anti-PSGL-1 treatment in vitro, had no impact on tumorigenesis. These findings show that PSGL-1 antibody targeting triggers lymphoma cell apoptosis and substantiates PSGL-1 as a potential target for lymphoma therapy.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3257","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venetoclax plus daunorubicin and cytarabine in newly diagnosed acute myeloid leukemia patients: A propensity score-matched analysis","authors":"Rong Wang,&nbsp;Yi Zhang,&nbsp;Jie Chang,&nbsp;Huafeng Wang,&nbsp;Yinjun Lou,&nbsp;Min Yang,&nbsp;Gaixiang Xu,&nbsp;Hongyan Tong,&nbsp;Wanzhuo Xie,&nbsp;De Zhou,&nbsp;Juying Wei,&nbsp;Wenyuan Mai,&nbsp;Xiujin Ye,&nbsp;Haitao Meng,&nbsp;Jie Jin,&nbsp;Hong-Hu Zhu","doi":"10.1002/hon.3260","DOIUrl":"10.1002/hon.3260","url":null,"abstract":"<p>Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy (DAV) has shown safety and efficacy in eligible patients with newly diagnosed acute myeloid leukemia (AML). However, there are no direct comparisons between DAV and 3 + 7 daunorubicin and cytarabine chemotherapy (DA) alone. We performed a propensity score-matched analysis to compare the outcomes of DAV group with historical DA group and identify the clinical and molecular characteristics of patients who might benefit from the DAV regimen. The DAV group had a higher Complete remission (CR) rate than the DA group (90% vs. 55%, <i>p</i> = 0.008). 25 (96%) patients in the DAV group had a higher MRD-negative CRc rate compared with 13 (62%) patients in the DA group (<i>p</i> = 0.006). After a median follow-up duration of 19.15 (IQR 17.13–21.67) months, the DAV group had an improved overall survival (<i>p</i> = 0.001) and event-free survival (<i>p</i> = 0.069), but not disease-free survival (<i>p</i> = 0.136). Collectively, DAV regimen induced high CR rates and deep MRD-negative CRc rates after one cycle of induction therapy, as well as prolonged the overall survival, in young adult patients with AML who were eligible for intensive chemotherapy. The addition of venetoclax to intensive chemotherapy should be considered in the future to achieve better survival advantages in eligible AML patients.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isatuximab in combination with carfilzomib and dexamethasone in 1q21+ patients with relapsed/refractory multiple myeloma: Long-term outcomes in the Phase 3 IKEMA study","authors":"Thierry Facon,&nbsp;Philippe Moreau,&nbsp;Ivan Špicka,&nbsp;Kenshi Suzuki,&nbsp;Kwee Yong,&nbsp;Joseph Mikhael,&nbsp;Taro Fukao,&nbsp;Kamlesh Bisht,&nbsp;Nicole M. Armstrong,&nbsp;Sandrine Macé,&nbsp;Marie-Laure Risse,&nbsp;Thomas Martin","doi":"10.1002/hon.3258","DOIUrl":"10.1002/hon.3258","url":null,"abstract":"<p>Gain/amplification of 1q21 (≥3 copies), a chromosomal abnormality frequently observed in multiple myeloma, can negatively affect prognosis, due to its involvement in resistance to anti-myeloma therapy and disease progression. In this updated subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285) in relapsed/refractory multiple myeloma (RRMM), we evaluated progression-free survival (PFS) and depth of response with the anti-CD38 antibody isatuximab plus carfilzomib-dexamethasone (Isa-Kd) versus Kd, in 1q21+ patients and related subgroups, at long-term follow-up (44.2 months). Our analysis included patients with 1q21+ (≥3 copies, with/without high-risk chromosomal abnormality [HRCA]), isolated 1q21+ (≥3 copies, without HRCA), gain(1q21) (3 copies, with/without HRCA), and amp(1q21) (≥4 copies, with/without HRCA). PFS benefit was achieved with Isa-Kd versus Kd in patients with 1q21+ (HR 0.58, 95% CI: 0.37–0.92), with isolated 1q21+ (HR 0.49, 95% CI: 0.27–0.92), with gain(1q21), or amp(1q21), consistent with the overall population and prior interim 1q21+ subgroup analyses. Median PFS with Isa-Kd versus Kd was 25.8 versus 16.2 months in 1q21+ patients and 38.2 versus 16.2 months in patients with isolated 1q21+. Clinically meaningful, higher rates of very good partial response or better, complete response or better (≥CR), minimal residual disease (MRD) negativity, and MRD negativity and ≥CR were reached with Isa-Kd versus Kd in patients with 1q21+, isolated 1q21+, gain(1q21), or amp(1q21). In Isa-Kd and Kd, the MRD negativity and ≥CR rate was 29.3% versus 15.4% in 1q21+ patients, 36.2% versus 12.9% in patients with isolated 1q21+, 27.9% versus 13.5% in patients with gain(1q21), and 31.3% versus 20.0% in patients with amp(1q21), respectively. In conclusion, addition of Isa to Kd in triplet combination therapy has shown PFS benefit and deeper responses, compared with Kd, in 1q21+ patients at higher risk of progression, including patients with isolated 1q21+, gain(1q21), and amp(1q21), thus supporting Isa-Kd an effective treatment option for patients with RRMM.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Occurrence of lymphoproliferative disorders during ruxolitinib treatment: May fedratinib be the turning point?","authors":"Andrea Duminuco,&nbsp;Antonella Nardo,&nbsp;Giuseppe A. Palumbo","doi":"10.1002/hon.3259","DOIUrl":"10.1002/hon.3259","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and prognosis of acute myeloid leukemia patients with Runt-related transcription factor 1 mutation: A single-center retrospective analysis","authors":"Lin-Ya Wang,&nbsp;Yao Li,&nbsp;Qian Jiang,&nbsp;Hao Jiang,&nbsp;Yu Wang,&nbsp;Lan-Ping Xu,&nbsp;Xiao-Hui Zhang,&nbsp;Kai-Yan Liu,&nbsp;Fei-Fei Tang","doi":"10.1002/hon.3256","DOIUrl":"10.1002/hon.3256","url":null,"abstract":"<p>This study aimed to investigate the clinical characteristics and prognosis of Runt-related transcription factor 1 (RUNX1) mutant acute myeloid leukemia (AML) patients by comparing the features of AML patients with or without RUNX1 mutation. We retrospectively analyzed 180 AML patients including 36 AML patients with mutant RUNX1(AML-RUNX1^mut) and 144 AML patients with wild-type RUNX1(AML-RUNX1^wt) were selected using the case-pair method(1:4). Compared to AML-RUNX1^wt, AML-RUNX1^mut showed higher frequency of ASXL1 (<i>p</i> &lt; 0.001), SRSF2 (<i>p</i> &lt; 0.001), BCORL1 (<i>p</i> &lt; 0.001), RAS (<i>p</i> = 0.010) mutations, and absent NPM1 mutations (<i>p</i> = 0.022). The 3-year overall survival (OS) and disease-free survival (DFS) of AML-RUNX1^mut and AML-RUNX1^wt were 73.1% versus 68.0% (<i>p</i> = 0.64) and 80.7% versus 71.6% (<i>p</i> = 0.37), respectively. AML-RUNX1^mut receiving allogeneic hematopoietic cell transplantation (allo-HSCT) showed better survival than those who did not receive allo-HSCT (3-year OS, 84.3% vs. 52.7%; <i>p</i> = 0.006). Multivariate analysis showed that EZH2 mutation (<i>p</i> = 0.003), white blood cell (WBC) ≥30 × 10⁹/L (<i>p</i> = 0.036) and age ≥60 years (<i>p</i> = 0.038) were significant independent risk factors for inferior OS of AML-RUNX1^mut; WBC ≥30 × 10⁹/L (<i>p</i> = 0.013) and DNMT3A mutation (<i>p</i> = 0.045) were significant independent risk factors for shorter DFS of AML-RUNX1^mut. In conclusion, AML-RUNX1^mut showed unique clinical characteristics, but the survival between AML-RUNX1^mut and AML-RUNX1^wt were comparable. EZH2 co-mutation, DNMT3A co-mutation, old age and high WBC count were associated with inferior survival of AML-RUNX1^mut. Allo-HSCT can significantly improve the prognosis of AML-RUNX1^mut.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139897933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying and addressing unmet clinical needs on the use of zanubrutinib in chronic lymphocytic leukemia: A consensus-based position paper from an ad hoc expert panel","authors":"Francesca Romana Mauro,&nbsp;Alessandra Tedeschi,&nbsp;Marzia Varettoni,&nbsp;Francesco Zaja,&nbsp;Giovanni Barosi,&nbsp;Pier Luigi Zinzani","doi":"10.1002/hon.3255","DOIUrl":"10.1002/hon.3255","url":null,"abstract":"<p>Zanubrutinib has been approved for treating patients with different lymphoproliferative disorders and now represents a significant breakthrough in treating relapsed/refractory and previously untreated patients with chronic lymphocytic leukemia (CLL). Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of zanubrutinib in approved indications may be challenging. This article presents the results of a group discussion among an ad hoc constituted panel of experts to identify and address unmet clinical needs (UCNs) in using zanubrutinib in patients with CLL. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. Panel members reviewed the results of first-line and upstream controlled trials in which the efficacy and toxicity profile of zanubrutinib and other BTK inhibitors were investigated in patients with CLL. Based on a critical discussion of data, the panel produced recommendations for using zanubrutinib and proposals for new studies to increase the evidence for the optimal treatment of patients with CLL. The recommendations given by the panel are intended for use not only by expert centers but, above all, by less experienced hematologists as well as general practitioners.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How receptor tyrosine kinase-like orphan receptor 1 meets its partners in chronic lymphocytic leukemia","authors":"Nayla Mouawad,&nbsp;Edoardo Ruggeri,&nbsp;Guido Capasso,&nbsp;Leonardo Martinello,&nbsp;Andrea Visentin,&nbsp;Federica Frezzato,&nbsp;Livio Trentin","doi":"10.1002/hon.3250","DOIUrl":"https://doi.org/10.1002/hon.3250","url":null,"abstract":"<p>Chronic lymphocytic leukemia (CLL) is the most common leukemia in western societies, recognized by clinical and molecular heterogeneity. Despite the success of targeted therapies, acquired resistance remains a challenge for relapsed and refractory CLL, as a consequence of mutations in the target or the upregulation of other survival pathways leading to the progression of the disease. Research on proteins that can trigger such pathways may define novel therapies for a successful outcome in CLL such as the receptor tyrosine kinase-like orphan receptor 1 (ROR1). ROR1 is a signaling receptor for Wnt5a, with an important role during embryogenesis. The aberrant expression on CLL cells and several types of tumors, is involved in cell proliferation, survival, migration as well as drug resistance. Antibody-based immunotherapies and small-molecule compounds emerged to target ROR1 in preclinical and clinical studies. Efforts have been made to identify new prognostic markers having predictive value to refine and increase the detection and management of CLL. ROR1 can be considered as an attractive target for CLL diagnosis, prognosis, and treatment. It can be clinically effective alone and/or in combination with current approved agents. In this review, we summarize the scientific achievements in targeting ROR1 for CLL diagnosis, prognosis, and treatment.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment-related toxicity disparities in adult Hispanic acute lymphoblastic leukemia patients receiving pegaspargase-based regimens: A multicenter electronic health research network study","authors":"Benjamin J. Lee,&nbsp;Shawn P. Griffin","doi":"10.1002/hon.3254","DOIUrl":"https://doi.org/10.1002/hon.3254","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence, risk factors, and outcome of asymptomatic central nervous system involvement in adult patients with acute myeloid leukemia","authors":"Marijana Virijevic,&nbsp;Nada Kraguljac-Kurtovic,&nbsp;Mirjana Mitrovic,&nbsp;Ljubomir Jakovic,&nbsp;Zoran Bukumuric,&nbsp;Nikola Pantic,&nbsp;Nikica Sabljic,&nbsp;Zlatko Pravdic,&nbsp;Mirjana Cvetkovic,&nbsp;Vesna Knezevic,&nbsp;Tijana Dragovic-Ivancevic,&nbsp;Irena Djunić,&nbsp;Jovan Rajic,&nbsp;Violeta Milosevic,&nbsp;Milena Todorovic-Balint,&nbsp;Ana Vidovic,&nbsp;Nada Suvajdzic-Vukovic","doi":"10.1002/hon.3253","DOIUrl":"10.1002/hon.3253","url":null,"abstract":"<p>Examination of central nervous system (CNS) involvement is not routine diagnostic practice in adult patients with acute myeloid leukemia (AML). Therefore, many asymptomatic patients with CNS involvement might go undetected. The effect of CNS involvement on the AML disease course is not well defined, with conflicting results regarding clinical outcome. This study aimed to determine the incidence of asymptomatic CNS involvement in AML estimated by multiparametric flow cytometry of cerebrospinal fluid (MFC-CSF) at diagnosis, the related potential risk factors, and prognosis. In total, 645 patients with de novo AML were screened; 183 (28.4%) of them fulfilled institutional practice for MFC-CSF analysis based on presence of CNS symptoms and/or clinical features. CNS symptoms and signs were observed in 8/183 (4.4%) patients, but most patients (175/183, 95.6%) were asymptomatic. In the asymptomatic group, 73/175 (41.7%) patients had positive or suspicious cerebrospinal fluid (CSF) findings categorized as CNS positive (CNS^pos) and 102/175 (58.3%) had normal CNS findings categorized as CNS negative (CNS^neg). The presence of leukemic blasts was confirmed in 81/183 (44.3%) patients; the total incidence of CNS involvement in the whole AML group was 12.6% (81/645). Compared with asymptomatic patients with CNS^neg, those with CNS^pos had a significantly higher frequency of lymphadenopathy, white blood cell count ≥30 × 10⁹/L, presence of the monocytic phenotype, and a high percentage of bone marrow (BM) blasts. The multivariate logistic regression model identified monocytic phenotype (<i>p</i> = 0.047) and high percentage of BM blasts (<i>p</i> = 0.042) as predictors for CNS^pos. CNS^pos did not affect overall survival in patients with AML. There was a higher incidence of CNS involvement in asymptomatic adult patients with de novo AML, emphasizing possible undervalued rates of CNS disease at diagnosis. Prospective studies should determine whether diagnostic lumbar puncture for MFC-CSF analysis and CNS prophylaxis could contribute to better selection and prognosis in this patient population.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liposomal-encapsulated doxorubicin supercharge-containing front-line treatment improves response rates in primary mediastinal large B-cell lymphoma and mediastinal gray zone lymphoma","authors":"Marco Picardi,&nbsp;Claudia Giordano,&nbsp;Novella Pugliese,&nbsp;Massimo Mascolo,&nbsp;Silvia Varricchio,&nbsp;Giancarlo Troncone,&nbsp;Elena Vigliar,&nbsp;Claudio Bellavicine,&nbsp;Martina Lamagna,&nbsp;Dario Lisi,&nbsp;Annamaria Vincenzi,&nbsp;Fabrizio Pane","doi":"10.1002/hon.3247","DOIUrl":"https://doi.org/10.1002/hon.3247","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139550241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}