Haematologica最新文献

{"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}

{"title":"Rethinking the feasibility and safety of venetoclax-obinutuzumab in chronic lymphocytic leukemia: non-traditional factors may play a role in clinical practice.","authors":"Anna Maria Frustaci,Andrea Galitzia,Mariano Lucignano,Lorena Appio,Jacopo Olivieri,Alessandro Sanna,Claudia Baraté,Fabrizio Pane,Luana Schiattone,Beatrice Casadei,Isacco Ferrarini,Amalia Figuera,Paolo Sportoletti,Giacomo Loseto,Caterina Stelitano,Andrea Visentin,Melania Celli,Francesca Romana Mauro,Massimiliano Palombi,Marta Coscia,Vanessa Innao,Riccardo Moia,Marina Motta,Filomena Russo,Monica Tani,Annalisa Arcari,Elia Boccellato,Chiara Borella,Enrico Capochiani,Angela Ferrari,Massimo Gentile,Roberta Giachetti,Annamaria Giordano,Martina Bullo,Enrico Lista,Luigi Malandruccolo,Maurizio Musso,Marzia Varettoni,Federico Vozella,Francesca Cibien,Michele Merli,Laura Nocilli,Maria Cristina Pasquini,Azzurra Anna Romeo,Valentina Rossi,Gloria Turri,Anna Vanazzi,Marina Cavaliere,Alessandro Gozzetti,Lara Crucitti,Moira Lucesole,Marina Deodato,Annamaria Tomasso,Arianna Zappaterra,Roberta Murru,Caterina Patti,Luca Laurenti,Alessandra Tedeschi","doi":"10.3324/haematol.2025.287799","DOIUrl":"https://doi.org/10.3324/haematol.2025.287799","url":null,"abstract":"The concept of fitness for novel agents in chronic lymphocytic leukemia (CLL) remains debated. Comorbidities and treatment-related logistics are increasingly recognized as key factors in treatment feasibility. Venetoclax-obinutuzumab (VO) has demonstrated efficacy in both fit and unfit patients in clinical trials, yet real-world data remain limited. This retrospective, multicenter study analyzed disease- and patient-related factors affecting VO management and outcomes in 271 patients. Fitness was assessed using comorbidity indices (CLL-CI, CIRS, CCI), ECOG-PS, and caregiver need. Adverse events (AEs) and treatment modifications were evaluated across four treatment phases. Median age was 66 years (19% ≥75); 83% had comorbidities, 34% required polypharmacy, and 10% needed caregiver support. Overall, 96% completed debulking, 89% the full regimen, while 11% discontinued due to toxicity (Tox-DTD). Grade ≥3 AEs occurred in 55%, tumor lysis syndrome in 6%, severe infusion-related reactions in 5%. Overall, 3.3% died during treatment. Unfit patients did not show a significantly higher risk of treatment modifications due to AEs. Dose adjustments were more frequent during debulking. None of the validated fitness scores predicted treatment feasibility or Tox-DTD. Global feasibility was impacted by age (p .002), prior malignancies (p .003), prolonged steroid pre-treatment (p.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"75 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488209","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":"Fecal microbiota transplantation for decolonization from multidrug-resistant bacteria in pediatric allogeneic hematopoietic stem cell transplantation recipients: a retrospective real-word data study.","authors":"Riccardo Masetti,Giovanni Barbara,Edoardo Muratore,Giovanni Marasco,Cesare Cremon,Antonella Marangoni,Patrizia Brigidi,Lorenza Putignani,Giulia Angelino,Francesco Quagliarella,Federica Galaverna,Davide Leardini,Tiziana Lazzarotto,Maria Gabelli,Edoardo Savarino,Marco Zecca,Maura Faraci,Arcangelo Prete,Alessandra Biffi,Franco Locatelli,Pietro Merli","doi":"10.3324/haematol.2025.288067","DOIUrl":"https://doi.org/10.3324/haematol.2025.288067","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"67 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488111","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":"Radiopsy: a prospective observational study on quantitative multiparametric whole-body magnetic resonance imaging to discriminate between smoldering and multiple myeloma.","authors":"Giacomo Feliciani,Emiliano Loi,Elena Amadori,Eleonora Antognoni,Andrea Prochowski Iamurri,Danila Diano,Daniele Bruno,Arrigo Cattabriga,Paola Caroli,Matteo Marchesini,Davide Bezzi,Delia Cangini,Federica Matteucci,Domenico Barone,Davide Nappi,Gerardo Musuraca,Michela Ceccolini,Sonia Ronconi,Irene Azzali,Giovanni Martinelli,Lorenzo Stefano Maffioli,Nicola Normanno,Anna Sarnelli,Alice Rossi,Claudio Cerchione","doi":"10.3324/haematol.2025.287563","DOIUrl":"https://doi.org/10.3324/haematol.2025.287563","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"5 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319777","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":"Randomized trial of anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide to prevent graft-versus-host disease in haploidentical transplantation.","authors":"Zheng-Li Xu,Ting-Ting Han,Xiao-Lu Zhu,Jing Liu,Meng Lv,Yu-Qian Sun,Xiao-Dong Mo,Yi-Fei Cheng,Lan-Ping Xu,Xiao-Hui Zhang,Xiao-Jun Huang,Yu Wang","doi":"10.3324/haematol.2025.287504","DOIUrl":"https://doi.org/10.3324/haematol.2025.287504","url":null,"abstract":"The combination of anti-thymocyte globulin (ATG) and posttransplant cyclophosphamide (PTCy) appears to be a potentially effective graft-versus-host disease (GVHD) prevention strategy for haploidentical transplantation. However, the majority of the evidence originated from retrospective studies without uniform protocols. Our previous findings indicated that 10 mg/kg ATG plus low-dose PTCy could decrease GVHD among high-risk populations transplanted from maternal or collateral relatives. We designed an open-label, phase III, randomized controlled trial to compare patients receiving granulocyte colony-stimulating factor (G-CSF)/ATG-based haploidentical transplantation with or without low-dose PTCy (14.5 mg/kg on days 3 and 4) in nonmaternal, noncollateral haploidentical transplants from fathers, children or siblings. A total of 66 patients were randomly assigned to ATG-PTCy (n=44) or ATG (n=22) when the first interim analysis was performed. The interim analysis revealed that the 100-day cumulative incidences (CI) of grade II-IV (18.2% [95% CI 6.6-29.7] vs. 18.2% [1.7-34.7]; P = 0.996) and III-IV acute GVHD (2.3% [95% CI 0-6.7] vs. 0; P = 0.480) were comparable between the ATG-PTCy and ATG cohorts, as was chronic GvHD at 1 year. The estimated 1-year disease free survival (DFS) rates were also similar between ATG-PTCy and ATG cohorts (95.5% [95% CI 89.5-100] vs. 95.2% [86.6-100]; P = 0.979). These results suggested that ATG/PTCy (low-dose) had no advantage over 10 mg/kg ATG-based prophylaxis in patients with haploidentical transplantation other than that of maternal donors or collateral relatives. Future work needs to focus on identifying which populations might benefit from the combined strategy in the context of G-CSF/ATG-based protocols.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"13 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319804","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}