Blood Neoplasia最新文献

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A novel 3-way translocation involving ETV6::IL3 drives AML with eosinophilia 涉及ETV6::IL3的新型三向易位可诱发伴有嗜酸性粒细胞增多的急性髓细胞性白血病
Blood Neoplasia Pub Date : 2025-02-21 DOI: 10.1016/j.bneo.2025.100079
Ariel Siegel , Joseph Tripodi , Dianna Hardatt , Brianna Kelly , Sebastian El Ghaity-Beckley , Michelle Becker , Brenton Francisco , Kayleen Bailey , Bruce Petersen , Douglas Tremblay , Jonathan Feld , Hannah Levavi , Marina Kremyanskaya , Alla Keyzner , Bridget K. Marcellino , Christian Salib , Amy S. Duffield , John Mascarenhas , Vesna Najfeld , Alan H. Shih
{"title":"A novel 3-way translocation involving ETV6::IL3 drives AML with eosinophilia","authors":"Ariel Siegel , Joseph Tripodi , Dianna Hardatt , Brianna Kelly , Sebastian El Ghaity-Beckley , Michelle Becker , Brenton Francisco , Kayleen Bailey , Bruce Petersen , Douglas Tremblay , Jonathan Feld , Hannah Levavi , Marina Kremyanskaya , Alla Keyzner , Bridget K. Marcellino , Christian Salib , Amy S. Duffield , John Mascarenhas , Vesna Najfeld , Alan H. Shih","doi":"10.1016/j.bneo.2025.100079","DOIUrl":"10.1016/j.bneo.2025.100079","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 2","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adult leukemia in Florida 2010-2019: diverse, aging population as an indicator for the United States
Blood Neoplasia Pub Date : 2025-02-16 DOI: 10.1016/j.bneo.2025.100078
Ming S. Lee ∗ , Rebecca E. Kaiser ∗ , Christopher D. Armstrong , David B. Dukenik , Nancy S. Elliott , Raymond R. Balise , Justin M. Watts , Mikkael A. Sekeres , Erin N. Kobetz , Justin Taylor
{"title":"Adult leukemia in Florida 2010-2019: diverse, aging population as an indicator for the United States","authors":"Ming S. Lee ∗ ,&nbsp;Rebecca E. Kaiser ∗ ,&nbsp;Christopher D. Armstrong ,&nbsp;David B. Dukenik ,&nbsp;Nancy S. Elliott ,&nbsp;Raymond R. Balise ,&nbsp;Justin M. Watts ,&nbsp;Mikkael A. Sekeres ,&nbsp;Erin N. Kobetz ,&nbsp;Justin Taylor","doi":"10.1016/j.bneo.2025.100078","DOIUrl":"10.1016/j.bneo.2025.100078","url":null,"abstract":"<div><h3>Abstract</h3><div>According to recent data released by the National Cancer Institute, Florida has the highest incidence of adult leukemia in the United States. There is limited population-based research on aging and sociodemographic disparities associated with leukemia in Florida, which can have a national impact on the assessment of leukemia burden. Using geocoded cancer data from the Florida Cancer Data System and population data from the US Census, this study evaluated socioeconomic and regional disparities associated with leukemia and found that leukemia disparities by race/ethnicity and rurality exist in Florida. The non-Hispanic White population had the highest incidence rates for most subtypes of leukemia, whereas the non-Hispanic Black population had the highest odds of dying from leukemia. Rural counties and urban neighborhoods with lower socioeconomic status were associated with higher mortality odds for leukemia. Leukemia-treating physician numbers were mismatched in regions in which patients with leukemia exhibit higher incidence and mortality odds. These results suggest that leukemia incidence rate in Florida is likely to remain among the highest in the United States due to population aging; however, physician shortages may exacerbate disparities and limit care in rural areas. Florida demographically looks like what the entire US population may be in the future and is therefore an indicator of the coming needs in the United States for increased leukemia diagnosis, treatment, and survivorship care. Larger national and international studies can build on this study by applying our methodology on a larger scale and can also be applied to other hematologic malignancies and other cancer types.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 2","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-cell sequencing reveals shared clonal signatures in nonmalignant B and tumor cells in T-prolymphocytic leukemia
Blood Neoplasia Pub Date : 2025-02-16 DOI: 10.1016/j.bneo.2025.100076
Caroline Hesselager , Ingrid Thörn , Millaray Marincevic , Claes Ladenvall , Jonas Almlöf , Sara Löfgren , Simone Weström , Helena Nord , Lesley-Ann Sutton , Lucia Cavelier , Panagiotis Baliakas , Rose-Marie Amini
{"title":"Single-cell sequencing reveals shared clonal signatures in nonmalignant B and tumor cells in T-prolymphocytic leukemia","authors":"Caroline Hesselager ,&nbsp;Ingrid Thörn ,&nbsp;Millaray Marincevic ,&nbsp;Claes Ladenvall ,&nbsp;Jonas Almlöf ,&nbsp;Sara Löfgren ,&nbsp;Simone Weström ,&nbsp;Helena Nord ,&nbsp;Lesley-Ann Sutton ,&nbsp;Lucia Cavelier ,&nbsp;Panagiotis Baliakas ,&nbsp;Rose-Marie Amini","doi":"10.1016/j.bneo.2025.100076","DOIUrl":"10.1016/j.bneo.2025.100076","url":null,"abstract":"<div><h3>Abstract</h3><div>This study aimed to elucidate the clonal origin and evolutionary dynamics of T-cell prolymphocytic leukemia (T-PLL) using targeted next generation sequencing (NGS) of paired samples from diagnosis and relapse. DNA from both nonmalignant and tumor cells was extracted from sorted cell fractions obtained from 16 patients with T-PLL. NGS was performed using a customized Haloplex gene panel comprising 19 genes recurrently mutated in T-PLL (<em>ATM</em> and <em>JAK/STAT</em> pathway). Droplet digital polymerase chain reaction was performed to confirm mutations detected by NGS with low variant allele frequencies. Single-cell analysis of genomic DNA combined with cell surface protein markers was performed using the Mission Bio Tapestri Platform. The most frequently mutated gene was <em>ATM</em> (n = 10) followed by <em>STAT5B</em> (n = 7), <em>JAK3</em> (n = 3), <em>EZH2</em> (n = 3), <em>BCOR</em> (n = 1), and <em>STAT6</em> (n = 1). Relapse samples were available for 9 of the 16 patients. Varying patterns of clonal shifts were observed between diagnosis and relapse (increase, decrease, both increase and decrease, and no change). The presence of pathogenic variants in <em>ATM</em>, <em>EZH2</em>, <em>STAT5B</em>, and <em>JAK3</em> in both normal sorted B cells and clonal T cells was confirmed. Single-cell analysis revealed shared mutations in both nonmalignant B and clonal T cells in 1 case. A pathogenic variant within the <em>ATM</em> gene of potential germ line origin was observed in 1 case. T-PLL exhibits variable patterns of clonal evolution between diagnosis and relapse. Single-cell multiomics analysis reveals shared mutational signatures in both nonmalignant B cells and clonal T cells. The role of germ line <em>ATM</em> mutations in the pathogenesis of T-PLL should be further explored.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 2","pages":"Article 100076"},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prognostic impact of RDI of vincristine in patients with DLBCL receiving R-CHOP: a supplementary analysis of JCOG0601
Blood Neoplasia Pub Date : 2025-02-16 DOI: 10.1016/j.bneo.2025.100077
Takahiro Nakashima , Tomotaka Suzuki , Ryunosuke Machida , Kazuyuki Shimada , Tsutomu Kobayashi , Dai Maruyama , Wataru Munakata , Shinsuke Iida , Ken Ohmachi , Tomohiro Kinoshita , Kiyoshi Ando , Hirokazu Nagai
{"title":"Prognostic impact of RDI of vincristine in patients with DLBCL receiving R-CHOP: a supplementary analysis of JCOG0601","authors":"Takahiro Nakashima ,&nbsp;Tomotaka Suzuki ,&nbsp;Ryunosuke Machida ,&nbsp;Kazuyuki Shimada ,&nbsp;Tsutomu Kobayashi ,&nbsp;Dai Maruyama ,&nbsp;Wataru Munakata ,&nbsp;Shinsuke Iida ,&nbsp;Ken Ohmachi ,&nbsp;Tomohiro Kinoshita ,&nbsp;Kiyoshi Ando ,&nbsp;Hirokazu Nagai","doi":"10.1016/j.bneo.2025.100077","DOIUrl":"10.1016/j.bneo.2025.100077","url":null,"abstract":"<div><h3>Abstract</h3><div>R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine [VCR], and prednisolone) is the standard of care for previously untreated patients with diffuse large B-cell lymphoma (DLBCL). However, some DLBCL survivors experience long-lasting VCR-related peripheral neuropathy (PN). VCR dose is usually reduced based on PN severity, but inconsistent results have been reported regarding the effect of VCR dose reduction on the prognosis of patients with DLBCL. To evaluate the clinical impact of the relative dose intensity (RDI) of VCR (RDI<sub>O</sub>), we conducted a supplementary analysis of JCOG0601, a randomized phase 2/3 trial in which R-CHOP and CHOP with 8 doses of weekly rituximab were compared for progression-free survival (PFS). Among 422 patients enrolled in JCOG0601, 401 who had received at least 6 courses of protocol treatment were eligible. PFS was not significantly different between patients with low RDI<sub>O</sub> (&lt;95% [n = 161]) and high RDI<sub>O</sub> (≥95% [n = 240]; <em>P</em> = .0679), although those with low RDI<sub>O</sub> tended to have poor PFS (3-year PFS, 83.7% vs 78.2%). Multivariable analysis revealed that the presence of B symptoms and high-intermediate or high International Prognostic Index (IPI) risk, but not RDI<sub>O</sub>, were associated with poor PFS. To our knowledge, this is the first study revealing VCR dose reduction may not be associated with poor PFS as much as the presence of B symptoms and high-intermediate or high IPI risk, using data from a prospective trial with rituximab plus 21-day cycles of CHOP. If the patients with DLBCL can complete rituximab plus CHOP treatment, VCR dose reduction due to toxicity may not significantly impair treatment efficacy. JCOG0601 was registered at <span><span>www.jcog.jp/en/trials</span><svg><path></path></svg></span> as #jRCTs031180139.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 2","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety landscape of bispecific antibody therapy in non-Hodgkin lymphoma: a meta-analysis
Blood Neoplasia Pub Date : 2025-02-01 DOI: 10.1016/j.bneo.2024.100061
Rodrigo Fonseca , Alex J. Liu , Blake T. Langlais , Diana Almader-Douglas , Holenarasipur R. Vikram , Talal Hilal
{"title":"Safety landscape of bispecific antibody therapy in non-Hodgkin lymphoma: a meta-analysis","authors":"Rodrigo Fonseca ,&nbsp;Alex J. Liu ,&nbsp;Blake T. Langlais ,&nbsp;Diana Almader-Douglas ,&nbsp;Holenarasipur R. Vikram ,&nbsp;Talal Hilal","doi":"10.1016/j.bneo.2024.100061","DOIUrl":"10.1016/j.bneo.2024.100061","url":null,"abstract":"<div><h3>Abstract</h3><div>Bispecific antibodies (BsAbs) have emerged as a novel immunotherapy option for the treatment of non-Hodgkin lymphoma; however; their safety profiles remain underexplored. We conducted a systematic review and meta-analysis to better delineate the safety profiles of BsAbs, focusing on the prevalence and rates of infection, neutropenia, cytokine release syndrome (CRS), and immune effector cell–associated neurotoxicity syndrome (ICANS). A comprehensive literature search led to the inclusion of 32 trials, with a total of 2192 patients. Median age of participants was 66 years (range, 55-84) with a median of 2 prior lines of therapy (range, 0-5). At a median follow-up of 9.4 months (range, 2.8-32 , the pooled prevalence of all-grade and grade ≥3 neutropenia was 38% and 26%, respectively, with all-grade and grade ≥3 infections occurring at a rate of 38% and 12%, respectively. The prevalence of all grade CRS was 48% but only 2% was grade ≥3, whereas ICANS was infrequent (5% all grade). Stratification revealed both increased all-grade neutropenia and infection rates with combination therapy in comparison to BsAbs monotherapy. Despite these variations, BsAbs demonstrated an overall manageable safety profile, suggesting their viability as a treatment option in the relapsed/refractory setting. Standardized safety reporting and vigilant monitoring are essential to optimize their clinical use and improve patient outcomes.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 1","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Real-world safety profile of therapy with ibrutinib or acalabrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma
Blood Neoplasia Pub Date : 2025-02-01 DOI: 10.1016/j.bneo.2024.100064
Ramsay Hafer , Francesco Iadevaia , Thomas Z. Rohan , Teresa Duong , Maria Poluch , Gina Keiffer , Michael Li , Andres Ferber , Luca Laurenti , Alan S. Khoo , Pierluigi Porcu
{"title":"Real-world safety profile of therapy with ibrutinib or acalabrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma","authors":"Ramsay Hafer ,&nbsp;Francesco Iadevaia ,&nbsp;Thomas Z. Rohan ,&nbsp;Teresa Duong ,&nbsp;Maria Poluch ,&nbsp;Gina Keiffer ,&nbsp;Michael Li ,&nbsp;Andres Ferber ,&nbsp;Luca Laurenti ,&nbsp;Alan S. Khoo ,&nbsp;Pierluigi Porcu","doi":"10.1016/j.bneo.2024.100064","DOIUrl":"10.1016/j.bneo.2024.100064","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 1","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enitociclib, a selective CDK9 inhibitor: in vitro and in vivo preclinical studies in multiple myeloma
Blood Neoplasia Pub Date : 2025-02-01 DOI: 10.1016/j.bneo.2024.100050
Son Tran , Patrick Sipila , Melanie M. Frigault , Beatrix Stelte-Ludwig , Amy J. Johnson , Joseph Birkett , Raquel Izumi , Ahmed Hamdy , Ranjan Maity , Nizar J. Bahlis , Paola Neri , Aru Narendran
{"title":"Enitociclib, a selective CDK9 inhibitor: in vitro and in vivo preclinical studies in multiple myeloma","authors":"Son Tran ,&nbsp;Patrick Sipila ,&nbsp;Melanie M. Frigault ,&nbsp;Beatrix Stelte-Ludwig ,&nbsp;Amy J. Johnson ,&nbsp;Joseph Birkett ,&nbsp;Raquel Izumi ,&nbsp;Ahmed Hamdy ,&nbsp;Ranjan Maity ,&nbsp;Nizar J. Bahlis ,&nbsp;Paola Neri ,&nbsp;Aru Narendran","doi":"10.1016/j.bneo.2024.100050","DOIUrl":"10.1016/j.bneo.2024.100050","url":null,"abstract":"<div><h3>Abstract</h3><div>Multiple myeloma (MM) is a cancer of plasma cells that remains incurable despite advances in treatment options. In this study, a library of 216 clinically feasible small-molecule inhibitors was screened to identify agents that selectively inhibit MM cell proliferation. Enitociclib, a cyclin-dependent kinase 9–specific small-molecule inhibitor, was found to be highly effective in decreasing cell viability and inducing apoptosis in 4 MM cell lines. Enitociclib inhibited the phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II at Ser2/Ser5 and repressed the protein expression of oncogenes c-Myc, myeloid cell leukemia-1 (Mcl-1), and proliferating cell nuclear antigen (PCNA) in MM cells. Additionally, enitociclib demonstrated synergistic effects with several anti-MM agents, including bortezomib, lenalidomide, pomalidomide, and venetoclax. These results suggest that enitociclib may represent a promising therapeutic option for the treatment of MM, either as a single agent or in combination with other anti-MM agents.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 1","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aberrant heterochromatin silences immune response genes in chronic lymphocytic leukemia
Blood Neoplasia Pub Date : 2025-02-01 DOI: 10.1016/j.bneo.2024.100059
Olivia M. Depies , Qianqian Guo , Yuan Gao , Sutapa Sinha , Zhenqing Ye , Weiguo Han , Kari G. Rabe , Mingma S. Hoel , Heather C. Darby , Chuanhe Yu , Esteban Braggio , Sameer A. Parikh , Susan L. Slager , Neil E. Kay , Zhiquan Wang
{"title":"Aberrant heterochromatin silences immune response genes in chronic lymphocytic leukemia","authors":"Olivia M. Depies ,&nbsp;Qianqian Guo ,&nbsp;Yuan Gao ,&nbsp;Sutapa Sinha ,&nbsp;Zhenqing Ye ,&nbsp;Weiguo Han ,&nbsp;Kari G. Rabe ,&nbsp;Mingma S. Hoel ,&nbsp;Heather C. Darby ,&nbsp;Chuanhe Yu ,&nbsp;Esteban Braggio ,&nbsp;Sameer A. Parikh ,&nbsp;Susan L. Slager ,&nbsp;Neil E. Kay ,&nbsp;Zhiquan Wang","doi":"10.1016/j.bneo.2024.100059","DOIUrl":"10.1016/j.bneo.2024.100059","url":null,"abstract":"<div><h3>Abstract</h3><div>Epigenetic alterations have been found in chronic lymphocytic leukemia (CLL), but the functional importance of these changes remains underexplored. Here, we characterized the genome-wide histone modification landscapes of CLL using patient-derived samples across the disease course. Compared with normal B cells, we found that the enhancers specifically lost in CLL B cells are associated with the downregulation of genes involved in immune response. Importantly, these lost enhancers exhibit an increased level of heterochromatin marks, including H3K9me3 and H3K27me3. Using the <em>EBF1</em> gene locus as an example, we demonstrated that acquired H3K9me3 contributes to enhancer silencing and associated gene suppression. We further found that this aberrant chromatin signature also exists in the CLL precursor stage monoclonal B-cell lymphocytosis (MBL) cells, implicating the importance of epigenetic silencing in CLL evolution. Finally, when treated with the Bruton tyrosine kinase inhibitor ibrutinib, these silenced enhancers are relatively stable during therapy compared with the CLL-gained enhancers. In summary, we described an epigenetic silencing mechanism mediated by the heterochromatin that persists throughout CLL disease development and treatment and which may increase the risk of severe infections in MBL and CLL.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 1","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Outcomes of follicular lymphoma with leukemic phase in the modern era: results from a large multicenter study
Blood Neoplasia Pub Date : 2025-02-01 DOI: 10.1016/j.bneo.2024.100063
Asaad Trabolsi , Sunwoo Han , Narendranath Epperla , Kaitlin Annunzio , Firas Baidoun , Muhamad Alhaj Moustafa , Dan Morgenstern-Kaplan , Peter Doukas , Frederique St-Pierre , Brittany McCall , Lindsey Fitzgerald , Jose Sandoval-Sus , Shivani Dalal , Isildinha M. Reis , Jennifer Rose Chapman-Fredricks , Seo-Hyun Kim , Cherry Au , Natalie B. Otto , Khaled Alhamad , Thomas Ollila , Juan Pablo Alderuccio ∗
{"title":"Outcomes of follicular lymphoma with leukemic phase in the modern era: results from a large multicenter study","authors":"Asaad Trabolsi ,&nbsp;Sunwoo Han ,&nbsp;Narendranath Epperla ,&nbsp;Kaitlin Annunzio ,&nbsp;Firas Baidoun ,&nbsp;Muhamad Alhaj Moustafa ,&nbsp;Dan Morgenstern-Kaplan ,&nbsp;Peter Doukas ,&nbsp;Frederique St-Pierre ,&nbsp;Brittany McCall ,&nbsp;Lindsey Fitzgerald ,&nbsp;Jose Sandoval-Sus ,&nbsp;Shivani Dalal ,&nbsp;Isildinha M. Reis ,&nbsp;Jennifer Rose Chapman-Fredricks ,&nbsp;Seo-Hyun Kim ,&nbsp;Cherry Au ,&nbsp;Natalie B. Otto ,&nbsp;Khaled Alhamad ,&nbsp;Thomas Ollila ,&nbsp;Juan Pablo Alderuccio ∗","doi":"10.1016/j.bneo.2024.100063","DOIUrl":"10.1016/j.bneo.2024.100063","url":null,"abstract":"","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 1","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A phase 1 study of interleukin-15 in combination with mogamulizumab in relapsed and refractory T-cell malignancies
Blood Neoplasia Pub Date : 2025-02-01 DOI: 10.1016/j.bneo.2024.100054
Max J. Gordon ∗ , Sigrid Dubois ∗ , Milos D. Miljkovic , Samuel Ng , Bonita Bryant , Rahul Lakhotia , Christopher Melani , Stefania Pittaluga , Kevin Conlon , Thomas Waldmann , Louis M. Staudt , Wyndham H. Wilson , Mark Roschewski
{"title":"A phase 1 study of interleukin-15 in combination with mogamulizumab in relapsed and refractory T-cell malignancies","authors":"Max J. Gordon ∗ ,&nbsp;Sigrid Dubois ∗ ,&nbsp;Milos D. Miljkovic ,&nbsp;Samuel Ng ,&nbsp;Bonita Bryant ,&nbsp;Rahul Lakhotia ,&nbsp;Christopher Melani ,&nbsp;Stefania Pittaluga ,&nbsp;Kevin Conlon ,&nbsp;Thomas Waldmann ,&nbsp;Louis M. Staudt ,&nbsp;Wyndham H. Wilson ,&nbsp;Mark Roschewski","doi":"10.1016/j.bneo.2024.100054","DOIUrl":"10.1016/j.bneo.2024.100054","url":null,"abstract":"<div><h3>Abstract</h3><div>Recombinant human interleukin-15 (rhIL-15) is an immunotherapeutic agent that enhances natural killer (NK) cells to augment the antibody-dependent cellular cytotoxicity (ADCC) of monoclonal antibodies. Mogamulizumab is a CC chemokine receptor 4–directed monoclonal antibody that exerts cytotoxicity through ADCC and depletes regulatory T cells within the tumor microenvironment. We conducted a phase 1 clinical trial of rhIL-15 in combination with mogamulizumab. Patients with relapsed or refractory adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides (MF), and Sezary syndrome (SS) received a fixed dose mogamulizumab, combined with escalating doses of rhIL-15 to identify the maximum tolerated dose (MTD). Six patients were enrolled, 4 with ATLL and 2 with MF/SS. The most common adverse events were rash, infection, and fever (67% of all). Two patients (33%) had grade 4 acute kidney injury, and in 25% of cycles, grade 3 or higher anemia was present. The MTD was dose level 1. One patient with ATLL had a partial response despite receiving only 4 cycles because of grade 4 myositis. Circulating NK cells were increased in all patients during the first cycle and a rapid reduction in tumor cells within the peripheral circulation was noted. Ex vivo assessment demonstrated increased NK cell activation and increased cell lysis in the presence of monoclonal antibodies after only 5 days. Our small study suggests that rhIL-15, in combination with mogamulizumab, leads to effector NK cell activation and regulatory T-cell depletion but has an unfavorable safety profile. Future development of combinations of immunotherapy that target the microenvironment in relapsed or refractory T-cell lymphomas remains rational. This trial was registered at <span><span>www.ClinicalTrials.gov</span><svg><path></path></svg></span> as #NCT04185220.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 1","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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