Haematologica最新文献

{"title":"Adverse prognostic impact of <i>KIT</i> exon 17 mutations despite negative flow cytometric measurable residual disease in pediatric acute myeloid leukemia with <i>RUNX1::RUNX1T1</i>.","authors":"Shota Kato, Shin-Ichi Tsujimoto, Jun Matsubayashi, Shotaro Iwamoto, Hidefumi Hiramatsu, Yusuke Okuno, Tatsuya Kamitori, Kentaro Ohki, Takao Deguchi, Nobutaka Kiyokawa, Motohiro Kato, Junko Takita, Shiro Tanaka, Souichi Adachi, Daisuke Tomizawa, Norio Shiba","doi":"10.3324/haematol.2024.286243","DOIUrl":"10.3324/haematol.2024.286243","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"251-256"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132567","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":"Outcomes of patients with primary central nervous system lymphoma following CD19-targeted chimeric antigen receptor T-cell therapy.","authors":"Santiago Mercadal, Kwang Woo Ahn, Mariam Allbee-Johnson, Siddhartha Ganguly, Praveen Ramakrishnan Geethakumari, Sanghee Hong, Adriana Malone, Hemant Murthy, Attaphol Pawarode, Alejandro R Sica, Melhem Solh, Celalettin Ustun, Mazyar Shadman, Craig S Sauter, Mehdi Hamadani, Alex F Herrera, Catherine J Lee","doi":"10.3324/haematol.2024.285613","DOIUrl":"10.3324/haematol.2024.285613","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"218-221"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132573","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":"Pirtobrutinib monotherapy in Bruton tyrosine kinase inhibitor-intolerant patients with B-cell malignancies: results of the phase I/II BRUIN trial.","authors":"Nirav N Shah, Michael Wang, Lindsey E Roeker, Krish Patel, Jennifer A Woyach, William G Wierda, Chaitra S Ujjani, Toby A Eyre, Pier Luigi Zinzani, Alvaro J Alencar, Paolo Ghia, Nicole Lamanna, Marc S Hoffmann, Manish R Patel, Ian Flinn, James N Gerson, Shuo Ma, Catherine C Coombs, Chan Y Cheah, Ewa Lech-Maranda, Bita Fakhri, Won Seog Kim, Minal A Barve, Jonathon B Cohen, Wojciech Jurczak, Talha Munir, Meghan C Thompson, Donald E Tsai, Katherine Bao, Nicholas A Cangemi, Jennifer F Kherani, Richard A Walgren, Hongmei Han, Amy S Ruppert, Jennifer R Brown","doi":"10.3324/haematol.2024.285754","DOIUrl":"10.3324/haematol.2024.285754","url":null,"abstract":"<p><p>Bruton tyrosine kinase inhibitors (BTKi) have transformed the treatment of B-cell malignancies, but intolerance has often led to their discontinuation. The phase I/II BRUIN study evaluated pirtobrutinib, a highly selective non-covalent (reversible) BTKi, in patients with relapsed / refractory B-cell malignancies (clinicaltrials.gov 03740529). Pirtobrutinib was investigated in 127 patients with intolerance to at least one prior BTKi therapy in the absence of progressive disease. The most common adverse event (AE) leading to BTKi discontinuation was cardiac disorders (N=40, 31.5%), specifically atrial fibrillation (N=30, 23.6%). The median follow-up was 17.4 months and the median time on pirtobrutinib was 15.3 months. The most common reasons for pirtobrutinib discontinuation were progressive disease (26.8%), AE (10.2%) or death (5.5%). The most frequent treatment-emergent AE were fatigue (39.4%) and neutropenia (37.0%). Among patients who discontinued a prior BTKi for a cardiac issue, 75% had no recurrence of their cardiac AE. No patient discontinued pirtobrutinib for the same AE that led to discontinuation of the prior BTKi. In 78 chronic lymphocytic / small lymphocytic lymphoma (CLL/SLL) and 21 mantle cell lymphoma (MCL) patients intolerant to prior BTKi, overall response rate to pirtobrutinib was 76.9% and 81.0%, respectively. Median progression-free survival for CLL/SLL was 28.4 months but was not estimable for MCL. These results suggest that pirtobrutinib was safe, well-tolerated, and an efficacious option in patients with prior BTKi-intolerance.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"92-102"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371708","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":"Outcome of 421 adult patients with Philadelphia-negative acute lymphoblastic leukemia treated under an intensive program inspired by the GIMEMA LAL1913 clinical trial: a Campus ALL study.","authors":"Davide Lazzarotto, Marco Cerrano, Cristina Papayannidis, Sabina Chiaretti, Federico Mosna, Nicola Fracchiolla, Patrizia Zappasodi, Silvia Imbergamo, Maria Ilaria Del Principe, Monia Lunghi, Federico Lussana, Matteo Piccini, Monica Fumagalli, Michelina Dargenio, Prassede Salutari, Fabio Forghieri, Teresa Giulia Da Molin, Massimiliano Bonifacio, Matteo Olivi, Fabio Giglio, Silvia Trappolini, Matteo Leoncin, Antonino Mule, Mario Delia, Crescenza Pasciolla, Francesco Grimaldi, Benedetta Cambo, Lidia Santoro, Fabio Guolo, Paola Minetto, Marzia Defina, Patrizia Chiusolo, Matteo Fanin, Endri Mauro, Lara Aprile, Carla Mazzone, Fabio Trastulli, Maria Ciccone, Marco De Gobbi, Alessandro Cignetti, Eleonora De Bellis, Valentina Mancini, Alfonso Piciocchi, Marco Vignetti, Giovanni Marsili, Irene Della Starza, Renato Fanin, Mario Luppi, Felicetto Ferrara, Giovanni Pizzolo, Renato Bassan, Robin Foa, Anna Candoni","doi":"10.3324/haematol.2024.285638","DOIUrl":"10.3324/haematol.2024.285638","url":null,"abstract":"<p><p>The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph- ALL) has significantly improved patients' prognosis. Within the Campus ALL network, we analyzed the outcome of adult Ph- ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial to compare the real-life data with the study results. We included 421 consecutive patients; median age 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94%, and measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high-risk (VHR) and MRD positive cases, transplanted (hematopoietic stem cell transplantation [HSCT]) patients had a significantly better DFS than non-HSCT patients (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs. 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large, real-life cohort of Ph- ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial (CR rate after C1, 94% vs. 85%, P=0.0004; 3-year OS, 67% vs. 67%, P=0.94; 3-year DFS, 57% vs. 63%, P=0.17). HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"55-67"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999770","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":"Unlocking the therapeutic potential of selective CDK7 and BRD4 inhibition against multiple myeloma cell growth.","authors":"Yao Yao, Shuhui Deng, Jessica Fong Ng, Mei Yuan, Chandraditya Chakraborty, Vera JoyWeiler, Nikhil Munshi, Mariateresa Fulciniti","doi":"10.3324/haematol.2024.285491","DOIUrl":"10.3324/haematol.2024.285491","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a plasma cell malignancy that is considered incurable despite the recent therapeutic advances. Effective targeted therapies are, therefore, needed. Our previous studies proved that inhibiting CDK7 impairs the cell cycle and metabolic programs by disrupting E2F1 and MYC transcriptional activities, making it an appealing therapeutic target for MM. Given that CDK7 and BRD4 operate in two distinct regulatory axes in MM, we hypothesized that targeting these two complementary pathways simultaneously would lead to a deeper and more durable response. Indeed, combination therapy had superior activity against MM cell growth and viability, and induced apoptosis to a greater extent than did single-agent therapy in both cell lines and patients' cells. This synergistic activity was also observed in Waldenström macroglobulinemia (WM) cells and with other inhibitors of E2F1 activity. Dual inhibition effectively impaired the MYC and E2F transcriptional programs and MM tumor growth and progression in xenograft animal models, providing evidence for the potential of combination therapy as a therapeutic strategy in MM and WM.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"153-162"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758388","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":"Risk of infections in multiple myeloma. A populationbased study on 8,672 multiple myeloma patients diagnosed 2008-2021 from the Swedish Myeloma Registry.","authors":"Cecilie Hveding Blimark, Kristina Carlson, Christopher Day, Sigrun Einarsdottir, Gunnar Juliusson, Moshtak Karma, Dorota Knut-Bojanowska, Gunnar Larfors, Ingemar Turesson, Mariana Villegas-Scivetti, Ingigerdur Sverrisdóttir","doi":"10.3324/haematol.2024.285645","DOIUrl":"10.3324/haematol.2024.285645","url":null,"abstract":"<p><p>In multiple myeloma (MM), advancements in treatments and toxicity management have enhanced survival rates. This, coupled with shifting age demographics in MM, necessitates an updated assessment of infection risks in MM patients compared to the general population. Using Swedish population-based registries, we investigated the incidence of infections in 8,672 Swedish symptomatic MM patients diagnosed 2008-2021 and 34,561 matched controls. Overall, MM patients had a 5-fold risk (hazard ratio [HR] =5.30; 95% confidence interval [CI]: 5.14-5.47) of developing a clinically significant infection compared to matched controls. Bacterial infections represented a 5-fold (HR=4.88; 95% CI: 4.70-5.07) increased risk, viral and fungal infections 7-fold compared to controls. The first year after MM diagnosis the risk of infections compared to controls was 7-fold (HR=6.95; 95% CI: 6.61-7.30) and remained elevated up to 5 years after the myeloma diagnosis. The risk of infection compared to controls remained 5-fold in MM patients with follow-up till 2022. Preceding MM diagnosis, the risk compared to matched controls was significantly increased up to 4 years before MM diagnosis (HR=1.16; 95% CI: 1.05-1.28). Among MM patients, 8% had died within 2 months of diagnosis and infection contributed to 32% of all deaths. After 1 year, 20% MM patients had died, and infection-related mortality was 27%. Our data constitute the largest population-based study to date on the risk of infections compared to the normal population in the era of modern MM therapies and confirms that infections still represent a major threat to patients and underscores importance of preventive strategies.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"163-172"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633296","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":"Oxygen release from hemoglobin has limited effects on mitochondrial respiration measured from red blood cells. Reply to the Comment on \"Increased retention of functional mitochondria in mature sickle red blood cells is associated with increased sickling tendency, hemolysis and oxidative stress\".","authors":"Antoine Stier, Sofia Esperti, Elie Nader, Damien Roussel, Philippe Connes","doi":"10.3324/haematol.2024.286361","DOIUrl":"10.3324/haematol.2024.286361","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"260-263"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999771","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":"The CLL hunters: finally, BTK got arrested.","authors":"Loic Ysebaert","doi":"10.3324/haematol.2024.286469","DOIUrl":"10.3324/haematol.2024.286469","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"110 1","pages":"1-3"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914644","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":"Respiratory syncytial virus and other vaccine-preventable infections in multiple myeloma. A population-based study on 8,672 myeloma patients diagnosed 2008-2021 from the Swedish Myeloma Registry.","authors":"Sigrun Einarsdottir, Ingigerdur Sverrisdottir, Mariana Villegas-Scivetti, Chris Day, Ingemar Turesson, Gunnar Juliusson, Markus Hansson, Gunnar Larfors, Cecilie Hveding Blimark","doi":"10.3324/haematol.2024.285161","DOIUrl":"10.3324/haematol.2024.285161","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"179-182"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456373","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":"Blinatumomab is associated with better post-transplant outcome than chemotherapy in children with high-risk, first-relapse B-cell acute lymphoblastic leukemia irrespective of the conditioning regimen.","authors":"Christina Peters, Angela Bruno, Carmelo Rizzari, Alessandra Brescianini, Arend Von Stackelberg, Christin Linderkamp, Yi Zeng, Gerhard Zugmaier, Franco Locatelli","doi":"10.3324/haematol.2024.285837","DOIUrl":"10.3324/haematol.2024.285837","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"234-238"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132569","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}