Haematologica最新文献

{"title":"Decitabine plus all-<i>trans</i> retinoic acid <i>versus</i> decitabine monotherapy for myelodysplastic syndromes with excess blasts: a multicenter, randomized controlled trial.","authors":"Xinping Zhou, Yanjuan Lin, Yan Gao, Zheng Ge, Li Huang, Jin Zhang, Hai Cheng, Guifang Ouyang, Fanjun Meng, Yulu Tian, Yuemin Kuang, Fengping Zhou, Lixia Sheng, Weimei Jin, Gaixiang Xu, Liya Ma, Li Ye, Chen Mei, Jian Li, Jie Jin, Hongyan Tong","doi":"10.3324/haematol.2025.288526","DOIUrl":"10.3324/haematol.2025.288526","url":null,"abstract":"<p><p>Despite standard treatment with hypomethylating agents, the prognosis of patients with higher-risk myelodysplastic syndrome (MDS) remains poor. All-trans retinoic acid (ATRA) has demonstrated promising efficacy in unfit patients with acute myeloid leukemia. This multicenter controlled trial randomized (1:1) untreated patients with MDS with excess blasts (MDSEB) to ATRA plus decitabine (ATRA at 25 mg/m2/day in 2 divided daily doses throughout the 28-day cycle plus decitabine at 20 mg/m2 on days 1-5) or decitabine alone (20 mg/m2 on days 1-5). The primary endpoint was the overall response rate within four treatment cycles. A total of 227 patients were randomized. Four patients who did not commence therapy were excluded from the modified intention-to-treat (mITT) analysis. The median patient age was 62 years (range, 19-81). The overall response rate was 78% (86/110) in the ATRA group versus 51% (58/113) in the decitabine group (odds ratio =3.40; 95% confidence interval [CI]: 1.90-6.09; P<0.001). The ATRA group also had a higher complete remission rate (23% vs. 12%; odds ratio =2.05; 95% CI: 1.02-4.25; P=0.042). With a median follow-up of 30.1 months, progression-free survival (PFS) was 14.9 months in the ATRA group versus 10.5 months in the decitabine group (hazard ratio [HR]=0.70; 95% CI: 0.51-0.97; P=0.03). The overall survival was 23.0 months and 19.3 months, respectively (HR=0.77; 95% CI: 0.54-1.09; P=0.137). The two groups did not differ in grade 3 or higher hematological adverse events. In conclusion, adding ATRA to decitabine increased the overall response rate and prolonged PFS in adult patients with MDS-EB without increasing hematological toxicity. This study was registered at Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR1800018307).</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1683-1693"},"PeriodicalIF":7.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556761","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":"Interleukin-6 in Castleman disease subtypes: look to tissues, not just blood.","authors":"Mariam Goubran, Luke Y C Chen","doi":"10.3324/haematol.2025.289031","DOIUrl":"10.3324/haematol.2025.289031","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1529-1531"},"PeriodicalIF":7.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451687","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":"Mutational profiling in acute myeloid leukemia.","authors":"Courtney D DiNardo","doi":"10.3324/haematol.2026.289405","DOIUrl":"10.3324/haematol.2026.289405","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"111 5","pages":"1511-1512"},"PeriodicalIF":7.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814238","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":"Clonal hematopoiesis and its progression to myeloid neoplasms: insights into risk, biology, and therapeutic strategies.","authors":"J Scott Beeler, Matthew J Walter, Kelly L Bolton","doi":"10.3324/haematol.2025.287488","DOIUrl":"10.3324/haematol.2025.287488","url":null,"abstract":"<p><p>Clonal hematopoiesis (CH) is defined by the clonal expansion of hematopoietic stem and progenitor cells harboring somatic mutations that confer a fitness advantage. CH is common with advancing age and becomes nearly ubiquitous in middle age. Although typically asymptomatic, CH is associated with an increased risk of hematologic malignancies particularly myeloid neoplasms (MN), diverse non-malignant conditions, and all-cause mortality. Over the past decade, research has provided major insights into the origins of CH. In addition to aging, CH is promoted by environmental exposures, inherited genetic predisposition, and acquired conditions. Large-scale population and longitudinal sequencing studies have identified determinants of clonal behavior. Characterization of the natural history of CH has enabled the development of risk stratification models to identify individuals with CH at high risk of progression to MN, thereby providing a rationale for selecting patient populations best suited for therapeutic intervention trials. Emerging strategies include targeting mutation-specific vulnerabilities, modulating inflammatory pathways, reducing genotoxic therapy-induced clonal selection, and repurposing agents with efficacy in MN. In this review, we summarize current knowledge of the risk factors underlying CH development, highlight recent advances in understanding the determinants of clonal behavior including progression to MN, and discuss emerging therapeutic approaches for preventing malignant transformation and clinical trial design considerations.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1536-1551"},"PeriodicalIF":7.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124768","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":"Ethnicity affects relapse-free survival in immunemediated thrombotic thrombocytopenic purpura.","authors":"Júlia Weisinger, Florian Blanchard, Benoit Suzon, Christophe Deligny, Jehane Fadlallah, François Provôt, Pascale Poullin, Manon Marie, David Ribes, Gabriel Choukroun, Yahsou Delmas, Elie Azoulay, Ygal Benhamou, Maximilien Grall, Jean-Michel Halimi, Moglie Le Quintrec, Aude Servais, Thomas Papo, Camille Lepart, Claire Cartery, Valérie Chatelet, Jean-Francois Augusto, Simon Ville, Pierre Perez, Loïc Lièvre, Mathieu Legendre, Anne Rumpler, Alexandre Hertig, Virginie Rieu, Arnaud Jaccard, Patricia Zunic, Laurent Gilardin, Nihal Martis, Sara Rovira Puig, Rutuja Gupte, Maria Del Mar Tolos Garcia, Margot Dierickx, Daniela Greco, Timon Albrecht, Andreea-Adela Icleanu, Raïda Bouzid, Bérangère Joly, Agnès Veyradier, Adrien Picod, Paul Coppo","doi":"10.3324/haematol.2025.288789","DOIUrl":"10.3324/haematol.2025.288789","url":null,"abstract":"<p><p>Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is caused by a severe, antibody-mediated deficiency of ADAMTS13 activity. The B-cell depleting agent rituximab is effective in restoring ADAMTS13 activity and therefore preventing relapses. However, the risk of relapse appears heterogeneous among patients, although the underlying causes are elusive. Preliminary reports suggested that African ancestry could be associated with decreased relapse-free survival (RFS). Data from the registry of the French National Thrombotic Microangiopathy Reference Center were used to further address the role of ethnicity on response and RFS after rituximab administration in the acute as well as in the preemptive setting. A total of 790 patients (134 patients of African ancestry and 656 patients of European ancestry) were included in the study. Time from rituximab administration to ADAMTS13 recovery was comparable between the two cohorts. Patients of African ancestry had inferior 3-year RFS after the first rituximab-treated episode compared to patients of European ancestry (P<0.05). In multivariate analyses, African ancestry was identified as an independent risk factor for relapse (hazard ratio [HR]=1.36; P<0.05), as well as male sex (HR=1.21; P<0.05) and type of index episode treated by rituximab (relapsed disease vs. initial episode, HR=1.62; P<0.05). Moreover, time to relapse shortened progressively after consecutive courses of rituximab, regardless of ethnicity (P<0.05). These results indicate that ethnicity affects RFS with patients of African ancestry relapsing earlier, suggesting that a closer ADAMTS13 monitoring might be necessary in high-risk patients.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1716-1724"},"PeriodicalIF":7.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932890","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":"Genetic testing guides therapy in children with refractory cytopenias.","authors":"Yael Gernez, Bindu Sathi, Latha Rao, Joseph D Hernandez, Bertil Glader, Alma-Martina Cepika, Elisabeth G Hoyte, Kirsten Mouradian, Deepika Singh, Rosa Bacchetta, May Chien, David B Lewis, Katja G Weinacht","doi":"10.3324/haematol.2025.288839","DOIUrl":"10.3324/haematol.2025.288839","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1907-1913"},"PeriodicalIF":7.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932948","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":"Menin inhibitor DS-1594b drives differentiation and induces synergistic lethality in combination with venetoclax in acute myeloid leukemia cells with rearranged mixed-lineage leukemia and mutated nucleophosmin-1.","authors":"Valerio Ciaurro, Vassilena Sharlandjieva, Anna Skwarska, Catherine Chahrour, Natalia Baran, Zhihong Zeng, Cassandra Ramage, Naval Daver, Bing Z Carter, Sovira Chaundhry, Palaniraja Thandapani, Maria Paola Martelli, Thomas A Milne, Marina Konopleva","doi":"10.3324/haematol.2024.286833","DOIUrl":"10.3324/haematol.2024.286833","url":null,"abstract":"<p><p>Mixed-lineage leukemia (MLL) rearrangements (MLLr) and nucleophosmin-1 (NPM1) mutations are associated with acute leukemias whose pathogenesis is critically influenced by protein-protein interactions between menin and MLL. We hypothesized that targeting the menin-MLL interaction using DS-1594b and blocking the anti-apoptotic BCL-2 protein using venetoclax may promote differentiation and enhance eradication of MLLr and NPM1-mutated leukemias models. We treated acute myeloid leukemia (AML) cell lines with MLLr, NPM1 mutations, other leukemias and primary samples from AML patients with venetoclax alone, DS-1594b alone, and their combination. We measured proliferation, viability, apoptosis, and differentiation using a variety of cellular assays, western blotting, and BH3 profiling. Treatment with DS-1594b and venetoclax exerted significant synergy, resulting in enhanced differentiation and inhibited proliferation across several cell lines. In the NPM1-mutated AML patient-derived xenograft model, DS-1594b single-agent treatment significantly extended survival. Importantly, compared with DS-1594b monotherapy, the combination of DS-1594b and venetoclax more profoundly reduced leukemic burden and prolonged mouse survival. Menin inhibition was the primary driver of transcription changes in this model and impacted the expression of anti-apoptotic regulators, providing a mechanistic explanation for the synergy observed between these drugs. Overall, we observed synergistic effects on differentiation induction and proliferation inhibition, both in vitro and in vivo. Together, our studies underscore the promise of this combination strategy as a novel therapeutic approach for improving treatment outcomes in patients with these specific genomic alterations.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1610-1624"},"PeriodicalIF":7.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451746","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":"<i>IDH2</i> mutation is associated with favorable outcome among older adults with newly diagnosed acute myeloid leukemia treated with hypomethylating agent-based therapy.","authors":"Fieke W Hoff, Ying Huang, Rina Li Welkie, Ronan T Swords, Elie Traer, Eytan M Stein, Tara L Lin, Maria R Baer, Vu H Duong, William G Blum, Martha L Arellano, Wendy Stock, Olatoyosi Odenike, Joshua F Zeidner, Rebecca L Olin, Catherine C Smith, Gary J Schiller, Emily K Curran, Shivani V Handa, Nyla A Heerema, Timothy Chen, Molly Martycz, Mona Stefanos, Sonja G Marcus, Leonard Rosenberg, Brian J Druker, Ross L Levine, Amy Burd, Ashley O Yocum, Uma M Borate, Alice S Mims, John C Byrd, Yazan F Madanat","doi":"10.3324/haematol.2025.288743","DOIUrl":"10.3324/haematol.2025.288743","url":null,"abstract":"<p><p>Mutations of isocitrate dehydrogenase (IDH) are recurrent in newly diagnosed acute myeloid leukemia (AML) and their prevalence increases with age. The prognostic impact of IDH mutations in AML remains controversial. IDH inhibitors generally have a favorable side-effect profile, making them an attractive option for older patients. This retrospective analysis aimed to describe the prevalence and prognostic impact of IDH mutations in a large cohort of newly diagnosed AML patients aged ≥60 years enrolled in the Beat AML clinical trial. A total of 1,023 patients were included. IDH mutations were detected in 28% of patients, including 9.7% with IDH1mut, 18.9% with IDH2mut, and 1.0% with mutations in both IDH1 and IDH2. IDH mutations frequently co-occurred with DNMT3A (38%), NPM1 (35%), and SRSF2 (34%) mutations. In patients treated with intensive chemotherapy, IDH mutations were not prognostic for overall survival (OS) (P=0.76), while OS was longer for patients with IDH2mut compared to IDHwt in patients treated with hypomethylating agent (HMA)-based therapy (median OS, 18.5 vs. 10.2 months, P<0.001). IDH1 was not significant for outcome. IDH2 remained prognostic for OS after exclusion of patients receiving an IDH inhibitor (hazard ratio=0.60, 95% confidence interval: 0.41-0.89). Outcomes with TP53 or myelodysplasia-related gene mutations were also better with an IDH co-mutation (P=0.043, and P=0.006, respectively). In patients treated with HMA plus venetoclax (N=243), IDHmut was not prognostic (P=0.42). The high prevalence of IDHmut and favorable impact in patients treated with HMA-based therapy supports studies investigating the addition of targeted therapies to HMA-based regimens for older patients with IDH-mutant AML; mut: mutated; wt: wild-type.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1625-1633"},"PeriodicalIF":7.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451594","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":"RNA modification, leukemia stem cell, selective vulnerability.","authors":"Fengbiao Zhou","doi":"10.3324/haematol.2026.301076","DOIUrl":"https://doi.org/10.3324/haematol.2026.301076","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769986","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":"Myeloid blast phase of chronic myeloid leukemia with co-occurring t(11;12)(p15;q13)/<i>NUP98</i>::<i>HOXC12</i>: a novel <i>NUP98</i> fusion partner.","authors":"Azeem Khan, Jie Xu, Beenu Thakral, Gokce Altay Toruner, L Jeffrey Medeiros, Lianqun Qiu","doi":"10.3324/haematol.2025.300433","DOIUrl":"https://doi.org/10.3324/haematol.2025.300433","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770003","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}