Haematologica最新文献

{"title":"Asciminib for Philadelphia chromosome positive leukemias.","authors":"Timothy P Hughes,Deborah L White,David T Yeung","doi":"10.3324/haematol.2024.286798","DOIUrl":"https://doi.org/10.3324/haematol.2024.286798","url":null,"abstract":"Twenty-five years after the introduction of imatinib, we have entered a new era of therapy for Chronic Myeloid Leukemia (CML). Despite the development of second and third generation (2G and 3G) tyrosine kinase inhibitors (TKIs), their impact have been incremental in improving outcomes for CML patients. While frontline use of 2G TKIs have improved molecular response rates and reduced progression to blast phase, there has been no improvement in overall survival compared to imatinib, likely due to the higher toxicity and consequent higher non CML-related mortality. Imatinib remains the most prescribed therapy for CML worldwide, despite it being the least potent TKI and most prone to resistance and progression. Asciminib, the first STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor, binds to the myristoyl pocket of BCR::ABL1. Its specificity minimises off-target toxicity which enables asciminib to finally break this frustrating link between potency and toxicity. After a decade of clinical trials, both in patients with resistance and intolerance to two or more TKIs, and more recently in the frontline setting, asciminib is fulfilling its early promise of a more rapid and reliable pathway to long-term disease control with minimal toxicity. There are however some unexpected challenges when using asciminib that require further investigation. In this Spotlight we review the key studies and outline the potential impact and current limitations of this first STAMP inhibitor in the CML setting and in other leukemias where ABL1 or ABL2 is the key target.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"21 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488148","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":"Use of second-line and beyond maintenance therapies in adult patients with primary immune thrombocytopenia in Europe: a parallel study of six prospective multicenter national registries.","authors":"Guillaume Moulis,Frederick Chen,Giuseppe Carli,Waleed Ghanima,Karolin Trautmann-Grill,Thomas Stauch,Alexandra Schifferli,Haroon Miah,Manuela Rueter,Lisanna Ghiotto,Riccardo Tomasello,Annabell Georgi,Vickie McDonald,Francesco Zaja,Heidi Hassel Pettersen,Thomas Kühne,Maria Luisa Lozano,Tomás José González-López,Drew Provan,Marc Michel,Nichola Cooper,Francesco Rodeghiero","doi":"10.3324/haematol.2025.287408","DOIUrl":"https://doi.org/10.3324/haematol.2025.287408","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"243 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488167","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":"Early detection and management of extracranial arteriopathy reduces the incidence of silent cerebral infarcts in sickle cell anemia: a long-term prospective cohort study.","authors":"Francoise Bernaudin,Cecile Arnaud,Annie Kamdem,Jenny Youn,Manuela Vasile,Isabelle Hau,Fouad Madhi,Aline Malterre,Celine Delestrain,Ralph Epaud,Camille Jung,Suzanne Verlhac","doi":"10.3324/haematol.2025.287720","DOIUrl":"https://doi.org/10.3324/haematol.2025.287720","url":null,"abstract":"Previous reports about the Creteil newborn-cohort (1988/Apr-2007) showed that the risk of silent cerebral infarcts (SCI) remained high (37.1%) by age 14 in children with sickle cell anemia (SCA) and intracranial time-averaged mean maximum velocity (TAMMV)≥200cm/s despite chronictransfusion. Systematic assessment of extracranial internal carotid artery (eICA) since June-2011 revealed that SCI-risk is associated with chronic or acute anemia and eICA-stenosis. Based on these results, SCA-children with eICA-TAMMV≥200cm/s or eICA-stenosis were placed on chronictransfusion and considered for allogeneic stem-cell transplantation (alloSCT). SCA-children with 160-199cm/s eICA-TAMMV were maintained on hydroxyurea. We hypothesized that detection/management of eICA-arteriopathy and wider use of hydroxyurea could reduce SCI-incidence. Comparison between the new cohort (May-2007/Dec-2014) eICA-assessed before age 4 with wider but not systematic use of hydroxyurea and the earlier cohort (1988/Apr-2007) never eICAassessed until the 2008 update, revealed a significant reduction of SCI-risk (Log-Rank, P=.009) associated with eICA-assessment but not with wider use of hydroxyurea. eICA-TAMMVs≥160cm/s, even with no eICA-stenosis, were risk-factors for SCI, suggesting that all SCA-children with eICATAMMV≥ 160cm/s should be placed on chronic-transfusion. Hydroxyurea initiation at an early age was associated with lower intracranial-arteriopathy incidence, but not with lower eICA-arteriopathy and SCI-incidence. In the overall cohort (1988-2014), including 332 SCA-children, all assessed/managed for eICA-arteriopathy after 2011, the cumulative-SCI-incidence by age 14 was 25.0% (95%CI:19.0%-31.0%). SCI-risk was associated with being older at first-neck-MRA and having high MCV on hydroxyurea. While the impact of hydroxyurea on SCI-incidence remains unclear, making controlled trials necessary, eICA-arteriopathy management by intensive therapy is effective at improving SCIprevention.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"17 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488157","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":"An aggressive hematolymphoid neoplasm with homozygous SMARCB1 loss shows response to EZH2 inhibition.","authors":"Iman Sarami,Amy S Duffield,Suchitra Sundaram,Douglas I Lin,Christian Salib,Shafinaz Hussein,Siraj El Jamal,Nasrin Ghesani,Busra Cangut,Bruce E Petersen","doi":"10.3324/haematol.2024.285776","DOIUrl":"https://doi.org/10.3324/haematol.2024.285776","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"46 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488150","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":"Germline and somatic genetic landscape of pediatric myelodysplastic syndromes.","authors":"Lili Kotmayer,Alyssa L Kennedy,Marcin W Wlodarski","doi":"10.3324/haematol.2024.285700","DOIUrl":"https://doi.org/10.3324/haematol.2024.285700","url":null,"abstract":"Pediatric myelodysplastic syndromes (MDS) represent a rare group of clonal hematopoietic stem cell disorders accounting for ~5% of pediatric hematological malignancies. They are characterized by ineffective hematopoiesis, cytopenia, and dysplastic changes in the bone marrow with variable risk of progression to acute myeloid leukemia. Unlike adult MDS, pediatric cases predominantly present with hypocellular bone marrow, with monosomy 7 and trisomy 8 as the most common cytogenetic aberrations. Pediatric MDS can manifest as primary disease or arise secondary to classical inherited bone marrow failure syndromes, prior cytotoxic therapy, or acquired aplastic anemia. In recent years, new germline syndromes have been identified in a substantial proportion of patients with \"primary\" MDS. The most common are GATA2 deficiency and SAMD9/SAMD9L syndromes, accounting for at least 7% and 8%, respectively. The somatic mutational landscape is different from adult MDS, with recurrent mutations affecting SETBP1, ASXL1, RUNX1, and RAS pathway genes (PTPN11, NRAS, KRAS, CBL), while mutations in spliceosome components and epigenetic regulators which are common in adults, are virtually absent in children. Monosomy 7 serves as a \"central hub\" in disease evolution, associating with somatic leukemia driver mutations. On the other hand, somatic UBTF-TD and NPM1 mutations define a subtype of MDS with excess blasts with predominantly normal karyotype without known germline predisposition. Hematopoietic stem cell transplantation is the only curative option for pediatric MDS. Understanding the unique genetic profile of pediatric MDS has implications for diagnosis, therapy, donor selection and longterm surveillance, particularly for patients with germline predisposition syndromes. This review discusses current classification systems (WHO and ICC), provides a detailed overview of the germline and somatic genetic landscape of pediatric MDS, and highlights clinical implications of these genetic alterations.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"243 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488210","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":"Sugar free transforming growth factor β1 increases the fitness of myelodysplastic neoplasm / acute myeloid leukemia cells.","authors":"Eric Solary","doi":"10.3324/haematol.2025.288156","DOIUrl":"https://doi.org/10.3324/haematol.2025.288156","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"635 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488158","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":"Macrophages promote aberrant DNA repair in multiple myeloma via the CXCL5/8-CXCR2 axis.","authors":"Mengmeng Dong,Donghua He,Jinna Zhang,Haimeng Yan,Haoguang Chen,Enfan Zhang,Yili Feng,Jingsong He,Xi Huang,Guoqiao Chen,Xiuna Sun,Fei Cheng,Huiyao Gu,Huanping Wang,Anyong Xie,Zhen Cai,Cai Lab","doi":"10.3324/haematol.2025.287312","DOIUrl":"https://doi.org/10.3324/haematol.2025.287312","url":null,"abstract":"Multiple myeloma (MM) is closely associated with abnormal DNA repair and genome instability. The bone marrow microenvironment, particularly myeloma associated macrophages (MΦs) is critical to the progression of MM. However, there is limited understanding on the role of MΦs in DNA repair in MM. Here, we found that MΦs regulated DNA repair in MM cells by the CXCL5/8-CXCR2 axis. By promoting non-homologous end joining rather than homology-directed repair, MΦs increased the probability of chromosomal translocations in MM cells. Furthermore, clinical data confirmed that MΦs are closely associated to the increased genetic variations of MM patients' primary cells. The study elucidates a mechanism by which MΦs regulates DNA repair in MM in the microenvironment and provides a potentially new target to counter MM progression.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"13 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488153","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":"Understanding infectious complications in patients with lower risk myelodysplastic syndromes: a step towards improving survival.","authors":"Guillermo Garcia-Manero","doi":"10.3324/haematol.2025.287847","DOIUrl":"https://doi.org/10.3324/haematol.2025.287847","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"36 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488154","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":"Severe toxicity and poor efficacy of reinduction chemotherapy are associated with overall poor outcomes in relapsed B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group AALL1331 trial.","authors":"Laura E Hogan,Teena Bhatla,Xinxin Xu,Lia Gore,Elizabeth A Raetz,Deepa Bhojwani,David T Teachey,Stephen P Hunger,Mignon L Loh,Patrick A Brown,Lingyun Ji","doi":"10.3324/haematol.2025.287386","DOIUrl":"https://doi.org/10.3324/haematol.2025.287386","url":null,"abstract":"Children's Oncology Group AALL1331 utilized an intensive chemotherapy induction (Block 1) based on UK ALLR3 induction for children, adolescents, and young adults with acute lymphoblastic leukemia in first relapse, followed by risk-stratified therapy. High/intermediate risk patients were subsequently randomized to receive 2 blocks of chemotherapy or 2 blocks of blinatumomab followed by hematopoietic stem cell transplant. Low risk patients were randomized to chemotherapy or chemotherapy cycles intercalated with three blinatumomab blocks. Patients who had an early treatment failure were eligible to receive blinatumomab for up to 2 salvage cycles. We reviewed Block 1 responses, risk stratification, randomization rates, adverse events (AE), and event-free survival and overall survival for all enrolled patients. AALL1331 enrolled 661 patients: 24 died during Block 1 and 42 experienced early treatment failure. Overall, 531/661 (80.3%) attained complete remission with 586 risk-assigned and only 471 were randomized. Of 532 patients with marrow involvement, 290 (54.5%) were minimal residual disease positive (≥0.01%) after Block 1. Grade 3/4/5 AE occurred in Block 1 in 44.9, 24.1, and 3.6% patients respectively, with febrile neutropenia, infections, and sepsis most frequent. Notably, 190 enrolled patients (28.7%) did not proceed with post-induction therapy, including 115 (17.4%) risk stratified but not randomized. These patients had dismal survival. More effective and less toxic reinduction strategies are needed for B-ALL in first relapse. Trial Registration Number: NCT02101853.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"52 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488155","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":"Revised renal stratification and progression models for predicting long-term renal outcomes in immunoglobulin light chain amyloidosis.","authors":"Muhammad Umaid Rauf,Steven Law,Marisa Santostefano,Philip N Hawkins,Aviva Petrie,Francesco Cappelli,Federico Perfetto,Yousuf Razvi,Aldostefano Porcari,Sriram Ravichandran,Adam Ioannou,Joshua Bomsztyk,Alessia Argirò,Costanza Gaudio,Elisabetta Antonioli,Alessandro Barilaro,Marco Delsante,Vittorio Di Maso,Maria G Chiappini,Olabisi Ogunbiyi,Oliver C Cohen,Ana Martinez-Naharro,Carol Whelan,Helen J Lachmann,Ashutosh D Wechalekar,Federico Alberici,Marianna Fontana,Marco Allinovi,Julian D Gillmore","doi":"10.3324/haematol.2025.287703","DOIUrl":"https://doi.org/10.3324/haematol.2025.287703","url":null,"abstract":"Renal prognosis in light-chain amyloidosis (AL) is determined by categorizing patients into three renal stages at diagnosis and assessing Renal Response or Renal Progression following chemotherapy after 6 months. We evaluated, in a test (N=1935) cohort of patients with renal AL amyloidosis who were followed for a median of 95 months, a modified 4-stage model where Renal Stage 2 was sub-categorized according to preserved (2A) or reduced (2B) estimated Glomerular Filtration Rate (eGFR). A hybrid model for evaluation of Renal Progression was also introduced, using an eGFR cut-off of 30ml/min/1.73 m2. These models were compared with existing models; namely those of Palladini and Kastritis, and results were validated in a multicenter cohort (N=438). The risk of progression to renal replacement therapy (RRT) increased progressively across all Renal Stages of the revised staging model (Hazard ratio [HR]: 3.25, 5.13, 10.66 for Stages 2A, 2B and 3 respectively vs Stage 1, each p.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"70 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488165","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}