Haematologica最新文献

{"title":"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.2025.287509","DOIUrl":"https://doi.org/10.3324/haematol.2025.287509","url":null,"abstract":"Older patients with classical Hodgkin lymphoma (cHL) have lower tolerance and inferior outcomes after standard chemotherapy regimens. To identify patient-derived indicators of frailty associated with outcome, we retrospectively analyzed patient and disease characteristics, treatment and outcome in a Norwegian population-based cohort of older (≥60 years) patients with cHL diagnosed 2000-2015. We included 279 patients (median age 69 years, range 60-90) treated with curative intent, defined as any typical cHL regimen with ≥50% standard doxorubicin dose in the first cycle. Treatment-related mortality was 8%, median progression-free (PFS) and overall survival (OS) were 7.1 years (95% confidence interval [CI] 5.0-9.3) and 8.7 years (95%CI 7.0-10.4), respectively, in the Norwegian cohort. Multivariable analyses identified patient-derived prognostic factors working independently of stage, histology and international prognostic score. We derived a frailty index ranging from 0-3 with one point each for age ≥70 years, Eastern Cooperative Oncology Group status ≥2 and a Cumulative illness rating scale in geriatrics score ≥8. Patients were categorized as fit (score 0, 34% of patients), unfit (score 1-2, 60%) and frail (score 3, 7%), with 5-year PFS of 74%, 49% and 11%, and 5-year OS of 86%, 52%, and 22% respectively. The proposed frailty score was validated in an external cohort of 792 similarly selected patients from the Swedish Lymphoma Register, where comorbidities were scored based on the Charlson comorbidity index (0-2 versus 3 or higher). In this comprehensive study, we develop a frailty score for elderly cHL patients to inform clinical decisions and prospective trials evaluating selective therapies for older patients.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"141 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872048","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":"Prophylactic and pre-emptive donor lymphocyte infusion in patients with acute myeloid leukemia and myelodysplastic syndrome: validation of current recommendations and proposal of a modified outcome assessment.","authors":"Giuliano Filippini Velázquez,Jan Frederic Weller,Anna Rubeck,Tobias Arndt,Stefan Schiele,Markus Mezger,Claudia Lengerke,Wolfgang Bethge,Martin Trepel,Gernot Müller,Maximilian Christopeit,Christoph Schmid","doi":"10.3324/haematol.2024.287206","DOIUrl":"https://doi.org/10.3324/haematol.2024.287206","url":null,"abstract":"Prophylactic and pre-emptive donor lymphocyte infusion (pro/preDLI) is used to prevent haematological relapse of AML and MDS after allogeneic stem cell transplantation. For lack of prospective trials, outcome reports, risk factor analyses and published recommendations for DLI administration had to rely on registry studies, frequently limited by inconsistent reporting and missing data. Therefore, we performed an extensive chart review on recipients of pro/preDLI in two German centers to investigate the clinical applicability of current guidelines in a well-defined cohort. Beyond, as outcome after pro/preDLI is unsatisfactorily described by conventional parameters, we constructed a model for treatment success, defined as leukaemia-free survival (LFS) without intensive immunosuppressive treatment for Graft-versus-Host-Disease (GvHD). Eighty-three patients had received proDLI (n=36), preDLI for incomplete chimerism (preDLIIC, n=27) or for persisting minimal residual disease/molecular relapse (preDLI-MRD, n=20). According to current guidelines concerning initial T cell doses and timing of DLI, 42% of patients had received DLI as recommended (standard-intensity), whereas 30%/28% had received DLI in lower/higher cell doses and/or at a later/earlier time point (low-/highintensity). Two-year rates of overall survival (OS), LFS, relapse incidence and non-relapse mortality within the entire cohort were 80%/67%/27%/8%. One-year rates of high-grade acute/chronic GvHD were 34%/27% among all patients and 53%/33% after high-intensity DLI. One-year treatment success rate were 72%/69% after low-/standard intensity, in contrast to 34% after high-intensity DLI. Apart from advanced disease at alloSCT, high-intensity DLI was the major risk factor for lower OS (HR=6.12), LFS (HR=5.43), higher aGvHD (HR=2.51), and lower treatment success (HR=0.41), supporting adherence to current recommendations.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"14 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872047","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":"Production of platelets in vitro in functionalised 3-dimensional scaffolds mimicking the bone marrow niche.","authors":"Holly R Foster,Maria Colzani,Guenaelle Bouet,Daniel Howard,Christian A Di Buduo,Nicole Müller-Sienerth,Amie K Waller,Yi Sun,Natalia Davidenko,Jennifer H Shepherd,Thomas Moreau,Amanda L Evans,Paolo M Soprano,Martin E M Parsons,Yumi Ying Sims,Meera Arumugam,Wardiya Afshar-Saber,Ernest Turro,Patricia B Maguire,Serena M Best,Ruth E Cameron,Alessandra Balduini,Gavin J Wright,Cedric Ghevaert","doi":"10.3324/haematol.2024.286758","DOIUrl":"https://doi.org/10.3324/haematol.2024.286758","url":null,"abstract":"The safety, quality and supply of donor-derived platelet units intended for transfusion have improved over the past decades but significant problems still remain. In vitroderived platelets offer a possible alternative but up-scaling production is hindered by our limited understanding of thrombopoiesis (the release of platelets by their mother cell, the megakaryocyte [MK]). Here, we have developed an integrated strategy aiming to mimic ex vivo the bone marrow physiological niche that promotes thrombopoiesis by mature MKs. The screening of a panel of 259 recombinant transmembrane proteins derived from cells known to promote platelet production through direct contact with MKs enabled us to show that ACVR1B, CRTAM, MUCEN and BTN1A1 improve platelet production from either cord blood- (ACVR1B) or pluripotent stem cells-derived (CRTAM, MUCEN and BTN1A1) MKs. Using two different methodologies, we functionalise either collagen- or silkbased 3-dimensional scaffolds and confirm increased functional platelet production by up to two-fold. This unbiased approach has allowed us to identify novel proteins whose role in platelet formation was previously unknown and highlights the potential gain of recreating the MK niche to allow in vitro platelets to become a viable alternative for transfusion.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"66 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871977","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":"S-adenosylmethionine addiction confers sensitivity to methionine restriction in KMT2A-rearranged acute lymphoblastic leukemia.","authors":"Trisha Tee,Titine J J Ruiter,Shuiyan Wu,Weiya Zhang,Dorette van Ingen Schenau,Maria Rodionova,Danique Wajon,Britt M T Vervoort,Kari J T Grunewald,Marjolein Bosma,Rico Hagelaar,John Baker-Hernandez,Ahmed Dahaoui,Pauline Schneider,Nanda M Verhoeven-Duif,Laurens T Van der Meer,Frank N Van Leeuwen","doi":"10.3324/haematol.2023.284869","DOIUrl":"https://doi.org/10.3324/haematol.2023.284869","url":null,"abstract":"Current intensive chemotherapy regimens have improved overall survival in pediatric acute lymphoblastic leukemia (ALL) but fail to cure some high-risk patient subgroups. We observed that lysine methyltransferase 2A (KMT2A)-rearranged leukemia, an aggressive subset with a dismal prognosis, is particularly vulnerable to perturbations of the methionine cycle. We demonstrate that this methionine dependency is driven by an increased need for S-adenosylmethionine (SAM) to maintain the hypermethylated state of KMT2A-r leukemias. Important pro-survival KMT2A-r target genes are repressed under methionine restriction, which, combined with other downstream metabolic changes, results in rapid cell death. FIDAS-5, an orally active methionine adenosyltransferase 2A (MAT2A) inhibitor that blocks SAM production, successfully impaired leukemia progression in patient-derived xenograft models, and a drug screen revealed strong synergy between MAT2A inhibition and histone deacetylase inhibitors. Our results identify the methionine cycle as a targetable vulnerability in KMT2A-r leukemia, which may increase the efficacy of epigenetic targeting agents.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"34 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871979","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":"The specific transcriptional profile and clonal selection of monoclonal gammopathy of undetermined significance-like behavior predict an exceptionally favorable prognosis in multiple myeloma.","authors":"Wenqiang Yan,Chen Qiu,Jieqiong Zhou,Jingyu Xu,Jian Cui,Yuntong Liu,Chenxing Du,Tengteng Yu,Shuaishuai Zhang,Weiwei Sui,Shuhui Deng,Yan Xu,Dehui Zou,Weiping Yuan,Lugui Qiu,Mu Hao,Yajing Chu,Gang An","doi":"10.3324/haematol.2025.287523","DOIUrl":"https://doi.org/10.3324/haematol.2025.287523","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"258 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872050","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":"Asparaginase dosing for acute lymphoblastic leukemia: more questions than answers.","authors":"Etan Orgel","doi":"10.3324/haematol.2025.287429","DOIUrl":"https://doi.org/10.3324/haematol.2025.287429","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"20 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872052","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":"A phase II study of ponatinib for prevention of relapse after allotransplantation in FLT3 internal tandem duplication mutation positive (FLT3-ITD+) acute myeloid leukemia: the PONALLO trial.","authors":"Patrice Chevallier,Anne Thiebaut,Sylvie François,Sylvain Chantepie,Marie-Thérèse Rubio,Hélène Labussiere-Wallet,Eolia Brissot,Natacha Maillard,Anne Huynh,Valérie Coiteux,Maxime Jullien,Alice Garnier,Amandine Le Bourgeois,Pierre Peterlin,Thierry Guillaume","doi":"10.3324/haematol.2025.287681","DOIUrl":"https://doi.org/10.3324/haematol.2025.287681","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"17 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846298","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":"Novel PROTAC to target FKBP12: the potential to enhance bone morphogenetic protein activity and apoptosis in multiple myeloma.","authors":"Ingrid Quist-Lokken,Mira Tilseth,Clara Andersson-Rusch,Md Abu Hanif,Michael Walz,Johanna Fredrikke Nordstrand Moen,Megan Anne Vik,Tobias Schmidt Slordahl,Anders Sundan,Felix Hausch,Toril Holien","doi":"10.3324/haematol.2024.287047","DOIUrl":"https://doi.org/10.3324/haematol.2024.287047","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"29 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846349","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":"Prognostic value of minimal residual disease detected by EuroFlow next-generation flow cytometry and next-generation sequencing in patients with multiple myeloma achieving complete response and receiving lenalidomide maintenance after autotransplant: a prospective comparison study.","authors":"Takeshi Yoroidaka,Hiroyuki Takamatsu,Ryota Urushihara,Mitsuhiro Itagaki,Satoshi Yoshihara,Kota Sato,Naoki Takezako,Shuji Ozaki,Kazuhito Suzuki,Kentaro Kohno,Tsuyoshi Muta,Morio Matsumoto,Yasushi Terasaki,Takeshi Yamashita,Shin-Ichi Fuchida,Jun Sakamoto,Tadao Ishida,Kenshi Suzuki,Hirokazu Murakami,Brian G M Durie,Kazuyuki Shimizu","doi":"10.3324/haematol.2025.287411","DOIUrl":"https://doi.org/10.3324/haematol.2025.287411","url":null,"abstract":"Novel agents inducing deeper responses have improved the prognosis of patients with multiple myeloma (MM). To assess minimal residual disease (MRD) and stratify patients achieving complete response (CR), advanced technologies such as EuroFlow next-generation flow cytometry (NGF) and next-generation sequencing (NGS) are increasingly utilized. This prospective study evaluated responses in newly diagnosed MM patients undergoing autologous stem cell transplantation (ASCT) followed by lenalidomide maintenance therapy across multiple Japanese medical centers. Patients achieving CR or stringent CR within 100-365 days post-ASCT were included. MRD levels in the bone marrow were assessed using both NGF and NGS (cutoff: 1×10-5) at three time points: 100-365 days, 1 year, and 2 years post-ASCT. A total of 52 patients were analyzed. MRD levels determined by NGF and NGS showed a strong correlation (r = 0.9722, P < 0.0001). After a median follow-up of three years, the three-year progression-free survival (PFS) and overall survival (OS) rates were 76.5% (95% confidence interval [CI], 62.3%-85.9%) and 96.2% (95% CI, 85.5%-99.0%), respectively. Patients with sustained MRD negativity for >6 months demonstrated superior three-year PFS compared to those without sustained MRD negativity, as measured by both NGF (100% vs. 67.6%; hazard ratio [HR] 0.06; 95% CI, 0.0005-0.50; P < 0.007) and NGS (90.5% vs. 72.2%; HR 0.23; 95% CI, 0.06-0.94; P = 0.048). These findings highlighted a strong correlation in the MRD levels assessed by NGF and NGS and validated that sustained MRD negativity was significantly associated with prolonged PFS. (Trial registered at UMIN 000022238).","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"102 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846356","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":"A phase I / IIa trial of PXS-5505, a novel pan-lysyl oxidase inhibitor, in advanced myelofibrosis.","authors":"Pankit Vachhani,Peter Tan,Anne-Marie Watson,Shang-Ju Wu,Ross Baker,Stanley Cheung,Sung-Eun Lee,Chih-Cheng Chen,Tsai-Yun Chen,Hui-Hua Hsiao,Jae Hoon Lee,Lucia Masarova,Shuh Ying Tan,Jana Baskar,Brett Charlton,Alison Findlay,Dieter Hamprecht,Wolfgang Jarolimek,Joanna Leadbetter,John Miller,Kristen Morgan,Amna Zahoor,Gabriela Hobbs","doi":"10.3324/haematol.2024.287231","DOIUrl":"https://doi.org/10.3324/haematol.2024.287231","url":null,"abstract":"Myelofibrosis (MF) is a progressive disease characterized by accumulation of extracellular matrix (ECM) in the bone marrow (BM) which impairs normal hematopoiesis. While Janus kinase (JAK) inhibitors reduce spleen volume and provide symptomatic improvement, they do not resolve BM fibrosis and may cause or exacerbate anemia and thrombocytopenia. An anti-fibrotic therapy capable of normalising BM microenvironment and function remains a significant gap in the current treatment landscape. MF is associated with elevated expression of lysyl oxidases; enzymes responsible for maturation of the most abundant ECM proteins, collagen and elastin. PXS-5505 is a novel pan-lysyl oxidase inhibitor designed to exert an anti-fibrotic mode of action by preventing the cross-linking of collagen and elastin. PXS5505-MF-101 is a multi-center phase 1/2a study of PXS-5505 in MF patients which included a dose escalation phase (DEP) and a cohort expansion phase (CEP). Primary objectives were to determine the safety and tolerability of PXS-5505 and to define dosing for future studies. The DEP demonstrated that the highest dose tested, 200 mg BID, was safe and achieved robust systemic reduction of lysyl oxidase activity; this dose was therefore selected for the CEP. Twentyfour patients (median age 72 years) with relapsed or refractory MF were recruited into the CEP and 54% (13/24) completed 24 weeks of treatment. PXS-5505 was well tolerated and reached steady state concentrations by Day 28. Over the 24-week treatment period preliminary indications of clinical efficacy, including a reduction in BM collagen, were evident. Overall, these data support continued investigation of PXS-5505.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846352","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}