Haematologica最新文献

{"title":"Chemotherapy-free combination of ibrutinib and obinutuzumab for untreated advanced follicular lymphoma: results of a phase II study from the German Lymphoma Alliance.","authors":"Christian Schmidt, Gabriel Scheubeck, Vindi Jurinovic, Martin Sökler, Roswitha Forstpointner, Christian Buske, Andreas Viardot, Ulrich Keller, Ullrich Graeven, Reinhard Marks, Mathias Hänel, Rüdiger Liersch, Jan Dürig, Christiane Pott, Eva Hoster, Michael Unterhalt, Wolfgang Hiddemann","doi":"10.3324/haematol.2024.287162","DOIUrl":"https://doi.org/10.3324/haematol.2024.287162","url":null,"abstract":"<p><p>Immunochemotherapy induces long-term response in patients with follicular lymphoma. However, toxicity of chemotherapy remains a relevant challenge. The Bruton's tyrosine kinase inhibitor ibrutinib has shown significant activity in patients with indolent B-cell lymphoma. Combining ibrutinib with obinutuzumab may therefore be an attractive chemotherapy free option. We conducted a prospective, single-arm, multicenter phase 2 trial to evaluate the chemotherapy-free regimen of obinutuzumab plus ibrutinib in patients with previously untreated advanced-stage follicular lymphoma. Patients received six 21-days cycles of ibrutinib and obinutuzumab for induction and 12 additional two-month cycles for maintenance. Primary endpoint was one-year progression-free survival (PFS). The study was powered to detect an improvement of 10 percent over the one-year PFS of 85%. A total of 98 patients was enrolled in the trial. Median follow-up was 5.5 years. After induction, 5 patients (5%) had a complete response (CR) and 82 (85%) a partial response (PR). The one-year PFS was 80%, missing the prospected improvement of a one-year PFS of 85% (p=0.93). Median PFS was 4.5 years, median duration of response and overall survival were not reached. The most common adverse events of grade 3/4 were neutropenia, lung infection, hypertension, fatigue, rash and thrombocytopenia. The trial failed the primary efficacy endpoint of the chemotherapyfree regimen of obinutuzumab and ibrutinib in follicular lymphoma patients. However, the combination achieved durable and deep responses and revealed an acceptable safety profile.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274727","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}

{"title":"Atypical acute promyelocytic leukemia with tripartite fusion gene <i>PML::RARG::LINE-L2a</i> is resistant to ATRA but sensitive to arsenic-based therapy.","authors":"Sanyun Wu, Yalan Yu, Xiang Lin, Xiaosu Zhou, Yuanyuan Zhou, Ping Luo, Hui Shen, Jing He, Li Liu, Xiaoyan Liu, Dong Lei Zhang, Yanan Liu, Hui Xiao, Fuling Zhou, Hongxing Liu, Zhanglin Zhang","doi":"10.3324/haematol.2025.287318","DOIUrl":"https://doi.org/10.3324/haematol.2025.287318","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274724","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}

{"title":"Metabolic epigenome targeting hits KMT2A-rearranged acute lymphoblastic leukemia.","authors":"Dirk Heckl, Eva Rettinger","doi":"10.3324/haematol.2025.287881","DOIUrl":"https://doi.org/10.3324/haematol.2025.287881","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274732","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}

{"title":"Recombinant human erythropoietin plus all-trans retinoic acid and testosterone undecanoate for the treatment of anemia in patients with lower-risk myelodysplastic syndromes: a multicenter, single-arm, prospective trial.","authors":"Chen Mei, Gaixiang Xu, Cuiping Zheng, Yaping Xie, Minming Li, Yanping Shao, Rongxin Yao, Shi Tao, Wei Jiang, Jun Guo, Zhiyin Zheng, Wei Wang, Xinping Zhou, Liya Ma, Li Ye, Yingwan Luo, Chunmei Yang, Wenjuan Yu, Wanzhuo Xie, Jie Jin, Hongyan Tong","doi":"10.3324/haematol.2024.287055","DOIUrl":"https://doi.org/10.3324/haematol.2024.287055","url":null,"abstract":"<p><p>Erythropoiesis-stimulating agents (ESAs) achieve hematological improvement-erythroid (HIE) in only 30% of ESA-naïve lower risk myelodysplastic syndrome (LR-MDS) patients with anemia, highlighting the need for developing novel drugs or new treatment strategies to improve the outcome of these patients. We conducted this multicenter, single-arm trial to investigate the efficacy and safety of a triple regimen consisting of recombinant human erythropoietin (rhEPO), all-trans retinoic acid (ATRA) and testosterone undecanoate in patients with anemia due to lower-risk MDS based on Revised International Prognostic Scoring System. Eligible patients received rhEPO 10000 IU/day, oral ATRA 25 mg/m2/day and oral testosterone undecanoate 80 mg twice daily for 12 weeks. The primary endpoint was the proportion of patients achieving HI-E during 12 weeks of treatment. Of 52 eligible patients, 32 (61.5%, 95%CI 48.0%-73.5%) achieved HI-E, meeting the primary endpoint. Fifteen patients (65.2% [15/23]) with baseline serum erythropoietin ≤500 IU/L had HI-E versus 58.6% of those (17/29) with baseline serum erythropoietin >500 IU/L. More patients with very low or low risk had HI-E than those with intermediate risk (73.3% vs. 45.5%, P = 0.041) and fewer patients with mutated ASXL1 had HI-E than those with wildtype ASXL1 (33.3% vs. 70.0%, P = 0.040). The regimen had an acceptable safety profile compatible with individual agents. In conclusion, the triple regimen of rhEPO combined with ATRA and testosterone undecanoate attained HI-E in approximately 61.5% of patients regardless of baseline serum EPO levels, supporting further development of this regimen for LR-MDS patients with anemia. This study was registered at CHICTR.ORG.CN as ChiCTR2000032845.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274734","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}

{"title":"Metabolic reprogramming by PRDM16 drives cytarabine resistance in acute myeloid leukemia.","authors":"Junji Ikeda, Hiroyoshi Kunimoto, Yusuke Saito, Shin-Ichi Tsujimoto, Masanobu Takeuchi, Ayaka Miura, Takayuki Kurosawa, Koichi Murakami, Ikuma Kato, Megumi Funakoshi-Tago, Akihiko Yokoyama, Norio Shiba, Souichi Adachi, Daisuke Tomizawa, Tomohiko Tamura, Shuichi Ito, Hideaki Nakajima","doi":"10.3324/haematol.2024.287265","DOIUrl":"https://doi.org/10.3324/haematol.2024.287265","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) patients with high PRDM16 expression frequently experience induction failure and have a poor prognosis. However, the molecular mechanisms underlying these clinical features remain elusive. We found that murine AML cells transformed by MLL::AF9 fusion and oncogenic short-isoform Prdm16 overexpression (hereafter, MF9/sPrdm16) exhibited resistance to cytarabine (AraC), but not to anthracycline, both in vitro and in vivo. Intriguingly, MF9/sPrdm16 cells displayed a gene expression signature of high oxidative phosphorylation (OxPHOS) and increased mitochondrial respiration. The inhibition of mitochondrial respiration with metformin or tigecycline abrogated AraC resistance in MF9/sPrdm16 cells via an energetic shift toward low OxPHOS status. Furthermore, sPrdm16 upregulated Myc and the glutamine transporter Slc1a5, activating TCA cycle and glutaminolysis. Of note, both OxPHOS and MYC-target gene signatures were significantly enriched in AML patient samples with high PRDM16 expression. Together, we showed that PRDM16 overexpression activates mitochondrial respiration through metabolic reprogramming via MYC-SLC1A5-Glutaminolysis axis, thereby conferring AraC resistance on AML cells. These results suggest that targeting mitochondrial respiration might be a novel treatment strategy to overcome chemoresistance in AML patients with high PRDM16 expression.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"0"},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274733","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}

{"title":"Altered mesenchymal and endothelial subsets in interstitial bone marrow and focal lesions in myeloma patients and SCID-hu mice.","authors":"Wen Ling, Maurizio Zangari, Frits Van Rhee, Bart Barlogie, Shmuel Yaccoby","doi":"10.3324/haematol.2025.287717","DOIUrl":"https://doi.org/10.3324/haematol.2025.287717","url":null,"abstract":"<p><p>In myeloma, the bone marrow (BM) stroma mediates tumor growth directly and indirectly through the alteration of BM niches. The mesenchymal and endothelial cell subsets altered in the interstitial BM and focal lesions (FLs) of patients newly diagnosed with myeloma, as well as in the myelomasupportive human bone of the SCID-hu mouse model, were identified using single-cell atlases and gene expression profiling. The mesenchymal compartment showed enriched cells reflecting matrix cancer-associated fibroblasts (CAFs) and vascular CAFs/pericytes in FLs compared to interstitial BM and in myeloma interstitial BM compared to healthy donors. Patients with myeloma possessed inflammatory mesenchymal stem cell (MSC) subsets that expressed genes resembling various CAFs, including antigen-presenting CAFs and genes composing the diagnostic three-gene MSCs score for myeloma. The vascular compartment in FLs showed reduced expression of genes representing specialized bone remodeling endothelial cells and upregulation of genes reflecting angiogenic endothelial cells. We identified stroma factor-expressing CYR61/CCN1+ myeloid cells that were detected in myeloma but not in donors' bones. CYR61/CCN1+ myeloid cells co-expressed CD14, and their numbers were lower in the interstitial BM of patients with high-risk versus low-risk disease, and rare in FLs. These cells were enriched in the BM aspirate lipid layer. The SCID-hu model showed changes in mesenchymal and endothelial cell subsets resembling clinical FLs, except for inflammatory mesenchymal cells, which were present in the model but suppressed in FLs. Overall, this study provides a comprehensive assessment of the altered stroma in myeloma and identifies previously unappreciated microenvironmental cell subsets.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274722","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}

{"title":"Blocking platelet glycoprotein V cleavage reduces bleeding in mouse models of <i>MYH9</i>-related disease.","authors":"Patricia Öftering, Juliane Baumann, Sarah Beck, Andreas Greinacher, Bernhard Nieswandt, Markus Bender","doi":"10.3324/haematol.2025.287542","DOIUrl":"https://doi.org/10.3324/haematol.2025.287542","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274726","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}

{"title":"Response to Comment on: A simplified frailty score predicts outcome in curatively treated older patients with classical Hodgkin lymphoma.","authors":"Kjersti Lia, Rasmus Rask Kragh Jørgensen, Per Wikman, Bente L Wold, Ninja Övergaard, Øystein Fluge, Unn-Merete Fagerli, Hanne Bersvendsen, Idun B Bø, Sameer Bhargava, Daniel Molin, Alexander Fosså","doi":"10.3324/haematol.2025.288284","DOIUrl":"https://doi.org/10.3324/haematol.2025.288284","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274735","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}

{"title":"Blinatumomab and better BCR::ABL1 inhibition begets better bone marrow transplant outcomes.","authors":"Marlise R Luskin, Jessica T Leonard","doi":"10.3324/haematol.2025.288068","DOIUrl":"https://doi.org/10.3324/haematol.2025.288068","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274725","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}

{"title":"Comprehensive evaluation of disease characteristics and outcomes of patients with extramedullary multiple myeloma in the modern era.","authors":"Megan Broughton, Subodh Bhatta, Doshi Sonali, Naresh Bumma, Abdullah M Khan, Srinivas Devarakonda, Elvira Umyarova, Don Benson, Ashley Rosko, Francesca Cottini","doi":"10.3324/haematol.2025.287545","DOIUrl":"https://doi.org/10.3324/haematol.2025.287545","url":null,"abstract":"<p><p>Multiple myeloma (MM) derives from the clonal proliferation of plasma cells, primarily residing in the bone marrow. However, MM cells can disseminate systemically, leading to osseous or soft tissue extramedullary disease (EMM) or plasma cell leukemia (PCL). The presence of EMM or PCL has historically been linked to poor prognosis and aggressive features. In this study, we analyzed 201 patients with EMM treated at our institution between January 1, 2010, and November 30, 2023. Among these patients, 25 had primary PCL, 19 had secondary PCL, 89 were diagnosed with EMM at the time of MM diagnosis, 29 developed EMM after therapy, and 39 had solitary plasmacytoma (SP), with 20 progressing into MM. Patients with EMM at the time of MM diagnosis or SP progressing to MM exhibited a median overall survival (OS) comparable to those with MM alone (7.5 years or not reached). However, the presence of EMM was associated with worse prognosis in specific groups: primary PCL (median OS: 26 months), secondary PCL (median OS: 1.6 months), and secondary EMM (median OS: 16 months). Additional prognostic features included high R-ISS (Revised International Staging System), chromosomal abnormalities (1q+, 17p deletion, and 13q deletion), and elevated lactate dehydrogenase values at presentation. While the site of EMM did not correlate with inferior outcomes, osseous SP increased the risk of progression to overt MM. In conclusion, the presence of EMM confers variable prognosis, emphasizing the need for more effective therapeutic strategies, particularly for patients with PCL or those developing EMM later during treatment.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274729","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}