Haematologica最新文献

{"title":"Real-world comparison of lisocabtagene maraleucel and axicabtagene ciloleucel in large B-cell lymphoma: an inverse probability of treatment weighting analysis with 3-year follow up.","authors":"Andrew J Portuguese, Jennifer J Huang, Yein Jeon, Mahnoosh Taheri, Aya Albittar, Emily C Liang, Alexandre V Hirayama, Erik L Kimble, Lorenzo Iovino, Christina Poh, Ajay K Gopal, Mazyar Shadman, Brian G Till, Filippo Milano, Aude G Chapuis, Folashade Otegbeye, Ryan D Cassaday, Ryan S Basom, Qian Vicky Wu, David G Maloney, Jordan Gauthier","doi":"10.3324/haematol.2024.287010","DOIUrl":"https://doi.org/10.3324/haematol.2024.287010","url":null,"abstract":"<p><p>Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are FDA- and EMAapproved chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory large B-cell lymphoma (LBCL). However, comparative real-world analyses of their efficacy and toxicity with extended follow-up are lacking. We conducted a retrospective study of 160 LBCL patients treated at the Fred Hutchinson Cancer Center with commercial liso-cel or axi-cel per standard of care. Using inverse probability of treatment weighting (IPTW) to mitigate treatment allocation bias and multivariable adjustments to minimize other sources of confounding, we assessed the impact of CAR T-cell product type on outcomes. Axi-cel was associated with significantly higher rates of cytokine release syndrome (CRS; G1+: adjusted OR [aOR] 4.27, p=0.004; G2+: aOR 2.88, p=0.006), immune effector cell-associated neurotoxicity syndrome (ICANS; G1+: aOR 2.10, p=0.048), and immune effector cell-associated hematotoxicity (ICAHT; G1+: aOR 8.09, p.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614728","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":"Regulation of immune responses to therapeutic factor VIII by transplacental delivery of Fc-fused immunodominant factor VIII domains or peptides.","authors":"Alejandra Reyes-Ruiz, Sandrine Delignat, Aurélien Azam, Victoria Daventure, Leslie Dourthe, Angelina Mimoun, Geneviève McCluskey, Maria T Georgescu, David Lillicrap, Jordan D Dimitrov, Sebastien Lacroix-Desmazes","doi":"10.3324/haematol.2024.287057","DOIUrl":"https://doi.org/10.3324/haematol.2024.287057","url":null,"abstract":"<p><p>Patients with severe hemophilia A (HA) often develop undesired immune responses to therapeutic factor VIII (FVIII) that hamper replacement therapy with FVIII-derived products. The transplacental delivery of two Fc-fused FVIII domains in pregnant HA mice was shown to induce partial FVIII-specific immune tolerance in the offspring. Here, we evaluated whether the transplacental delivery of Fc-fused FVIII (rFVIIIFc) induces complete immune tolerance towards FVIII. rFVIIIFc injected to pregnant HA mice was poorly transferred to the fetal circulation and failed to confer tolerance to exogenous FVIII in the offspring. The poor transplacental delivery of rFVIIIFc was associated with the large size of the molecule and with the presence of positive patches at the surface of FVIII. It was however independent from the capacity of rFVIIIFc to bind Fcô€€€ receptor or von Willebrand factor in the maternal circulation. Conversely, the transplacental delivery of Fc-fused A2 and C2 immunodominant domains of FVIII, as well as of Fc-fused molecules containing seven different immunodominant FVIII-derived peptides decreased the levels of anti-FVIII antibodies following FVIII replacement therapy in the offspring. Our study paves the way towards the development of engineered Fc-fused molecules able to efficiently cross the placenta and confer potent and long-lasting immune tolerance to protein therapeutics.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614730","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":"Impact of hematopoietic cell transplantation and quizartinib in newly diagnosed patients with acute myeloid leukemia and FMS-like tyrosine kinase 3-internal tandem duplications in the QuANTUM-First trial.","authors":"Richard F Schlenk, Pau Montesinos, Hee-Je Kim, Antonio Romero-Aguilar, Radovan Vrhovac, Elżbieta Patkowska, Pavel Žak, Po-Nan Wang, James Hanyok, Li Liu, Yasser Mostafa Kamel, Karima Imadalou, Arnaud Lesegretain, Jorge Cortes, Mikkael A Sekeres, Herve Dombret, Sergio Amadori, Jianxiang Wang, Alexander E Perl, Mark J Levis, Harry P Erba","doi":"10.3324/haematol.2024.286623","DOIUrl":"https://doi.org/10.3324/haematol.2024.286623","url":null,"abstract":"<p><p>QuANTUM-First (NCT02668653) was a randomized phase 3 trial in newly diagnosed FLT3-ITDQpositive acute myeloid leukemia (AML) patients treated with quizartinib or placebo plus standard induction and consolidation chemotherapy and/or allogeneic hematopoietic cell transplantation (allo-HCT), followed by single-agent maintenance therapy. We evaluated the impact of allo-HCT performed in first complete remission (CR1) or composite CR1 (CRc1) on overall survival (OS), considering treatment randomization. Post-hoc extended Cox regression multivariable analyses were conducted in patients who achieved CR/CRc by the end of induction, including allo-HCT in CR1/CRc1 as a time-dependent variable to identify prognostic and predictive factors for OS. There were 297 patients with CR by the end of induction (quizartinib, n=147; placebo, n=150); of these, 157 (52.9%) underwent allo-HCT in CR1 (quizartinib, n=84; placebo, n=73). There were 368 patients with CRc by the end of induction (quizartinib, n=192; placebo, n=176); of these, 196 (53.3%) underwent allo-HCT in CRc1 (quizartinib, n=110; placebo, n=86). Multivariable analyses revealed quizartinib treatment and allo-HCT in either CR1 (hazard ratio [HR]=0.553, 95% confidence interval [CI]=0.383Q0.798, P=0.0015 and HR=0.527, 95% CI=0.349Q0.796, P=0.0023, respectively) or CRc1 (HR=0.645, 95% CI=0.470Q0.886, P=0.0068 and HR=0.557, 95% CI=0.391Q0.793, P=0.0012, respectively) as significant predictive factors for a longer OS. No new safety signals were identified. Patients who underwent protocol-specified allo-HCT in CR1/CRc1 experienced post-allo-HCTQrelated complications, mostly grade ≥2 graft-versus-host disease, as expected. This posthoc analysis further supports quizartinib and allo-HCT in CR1/CRc1 as an efficacious and well-tolerated treatment strategy for newly diagnosed FLT3-ITDQpositive AML patients fit for intensive chemotherapy.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614723","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":"Leukemic presentation in nodal mantle cell lymphoma is characterized by frequent SOX11 negativity, a poor risk genomic landscape including higher <i>TP53</i> alterations, and worse overall survival.","authors":"Mingfei Yan, Shenon Sethi, Jyoti Kumar, Anita Kumar, Ahmet Dogan, Pallavi Galera","doi":"10.3324/haematol.2024.287108","DOIUrl":"https://doi.org/10.3324/haematol.2024.287108","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614724","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":"Safe platelet count for lumbar puncture: are we being overcautious?","authors":"Talha Badar","doi":"10.3324/haematol.2025.287359","DOIUrl":"https://doi.org/10.3324/haematol.2025.287359","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614704","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":"Enforcement of stem-cell dormancy by nucleophosmin mutation is a critical determinant of unrestricted self-renewal during myeloid leukemogenesis.","authors":"Maria Elena Boggio Merlo, Maria Mallardo, Lucilla Luzi, Giulia De Conti, Chiara Caprioli, Roman Hillje, Mario Faretta, Cecilia Restelli, Andrea Polazzi, Valentina Tabanelli, Angelica Calleri, Stefano Pileri, Pier Giuseppe Pelicci, Emanuela Colombo","doi":"10.3324/haematol.2024.286577","DOIUrl":"https://doi.org/10.3324/haematol.2024.286577","url":null,"abstract":"<p><p>Mutations in the NPM1 gene (NPMc+) and in the FLT3 gene (FLT3-ITD) represent the most frequent co-occurring mutations in Acute Myeloid Leukemia (AML), yet the cellular and molecular mechanisms of their cooperation remain largely unexplored. Using mouse models that faithfully recapitulate human AML, we investigated the impact of these oncogenes on pre-leukemic and leukemic hematopoietic stem cells (HSCs), both separately and in combination. While both NPMc+ and Flt3-ITD promote the proliferation of pre-leukemia HSCs, only NPMc+ drives extended selfrenewal by preventing the depletion of the quiescent HSC pool. Quiescent HSCs exist in a dynamic equilibrium between dormant and active states, which respectively support self-renewal and regenerative haematopoiesis. Transcriptional profiling of these dormant and active states revealed that not only does NPMc+ stimulate the transition from dormancy to activity but it also reinforces the dormant state, thereby ensuring the replenishment of dormant HSCs. Intriguingly, the coexpression of NPMc+ and Flt3-ITD engenders a novel phenotypic state within quiescent HSCs, whereby dormancy and activity co-exist within a single cell. We posit that this unique state fuels the in vivo expansion of self-renewing HSCs and facilitates the rapid selection of leukemiainitiating cells. Pharmacological inhibition of the dormancy-related TGFβ1 - pathway effectively reduces the self-renewal capacity of leukemia SCs and extends survival in our mouse models. Collectively, these findings demonstrate that enforcement of HSC dormancy is a critical determinant of unrestricted self-renewal during leukemogenesis and, as such, represents a compelling target for the development of novel anti-leukemic therapies.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614659","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":"Exploring new horizons in menin: it's bleximenib's turn.","authors":"Bradley Rockwell, Marina Konopleva","doi":"10.3324/haematol.2024.287142","DOIUrl":"https://doi.org/10.3324/haematol.2024.287142","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614720","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":"Bruton tyrosine kinase covalent inhibition shapes the immune microenvironment in chronic lymphocytic leukemia.","authors":"Daniel Medina-Gil, Laura Palomo, Víctor Navarro, Gonzalo Lázaro, Beatriz Martín-Mur, Cristina Hernández, Oriol Castells, Belén Sánchez, Pau Marc Muñoz-Torres, Carlota Pagès, Gemma Pujadas, Anna Esteve-Codina, Alba Cabirta, Christelle Ferrà, Miguel Alcoceba, Maria José Terol, Rafael Andreu, Mercè Martí, Pau Abrisqueta, Francesc Bosch, Marta Crespo","doi":"10.3324/haematol.2024.286663","DOIUrl":"https://doi.org/10.3324/haematol.2024.286663","url":null,"abstract":"<p><p>Continuous treatment with ibrutinib not only exerts tumor control but also enhances T cell function in patients with chronic lymphocytic leukemia (CLL). We conducted longitudinal multi-omics analyses in samples from CLL patients receiving ibrutinib upfront to identify potential adaptive mechanisms to Bruton tyrosine kinase (BTK) inhibition during the first 12 months of continuous therapy. We found that ibrutinib induced a decrease in the expression of exhaustion markers and the proportion of Tregs and Tfh cells normalized to levels observed in healthy donors. Functionally, the expression of genes related to activation, proliferation, differentiation, and metabolism were downregulated in T cells; after in vitro stimulation, proliferation capacity was only slightly modified by ibrutinib treatment, while cytokine production was increased. In CLL cells, we observed a downregulation of immunosuppression, adhesion, and migration proteins. Adaptation at molecular level, characterized by an increase in cancer cell fraction of CLL cells with mutated driver genes, was observed in around half of the patients and was associated with retained migrative capacity towards CXCL12/CXCR4 axis. Interestingly, BTK C481S mutations were detected as early as after 6 months of treatment, particularly enriched in subsets of malignant cells retaining migrative capacity. These CLL cells with potential migrative capacity under ibrutinib also exhibited a distinct transcriptomic profile including upregulation of mTOR-AKT and MYC pathways. We identified the high expression of TMBIM6 as a potential novel independent poor prognostic factor. Of note, BIA, a TMBIM6 antagonist, induced CLL cell apoptosis and synergized with ibrutinib. In summary, our comprehensive multiomics analysis of CLL patients undergoing ibrutinib therapy has unveiled early immunomodulatory effects on T cells and adaptative mechanisms in CLL cells. These findings can contribute to the identification of resistance mechanisms and the discovery of novel therapeutic targets.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614695","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":"Hemophilia is associated with accelerated biological aging.","authors":"Marina Trappl, Rafaela Vostatek, Manuel Salzmann, Daniel Kraemmer, Johanna Gebhart, Philipp Hohensinner, Ingrid Pabinger, Cihan Ay","doi":"10.3324/haematol.2024.286421","DOIUrl":"https://doi.org/10.3324/haematol.2024.286421","url":null,"abstract":"<p><p>Hemophilia is a rare X-linked bleeding disorder caused by mutations in the F8 or F9 gene (hemophilia A or B), leading to deficient factor VIII or IX proteins, respectively. Hemophilia-related complications caused by bleeding into the joints (the hallmark of hemophilia) and age-related comorbidities occur frequently and impact the functionality and quality of life of persons with hemophilia (PwH). Given the chronic nature of hemophilia, we hypothesized that hemophilia has an association with accelerated biological aging. Therefore, we investigated biological aging biomarkers, i.e. telomere length and mitochondrial DNA (mtDNA) copy number with a quantitative-PCR-based assay in PwH (n=99) and age- and sex-matched healthy controls (n=61). The association of telomere length and mtDNA copy number with hemophilia severity was investigated using ordinary-least-squares linear regression models allowing for interactions with chronological age. Telomere length (6.09 [4.79-7.68] kb vs. 10.07 [7.93-12.66] kb, p.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614721","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":"Plasma exchange for hyperammonemia-induced reduced consciousness after PEG-asparaginase in an adult patient with acute lymphoblastic leukemia.","authors":"Felix Klingler, Anika Forstreuter, Luisa Stegat, Sofie Kämereit, Felix Ullrich, Florian Udonta, Christian Krebs, Dominik Wichmann, Carsten Bokemeyer, Nicola Goekbuget, Walter Fiedler, Franziska Modemann","doi":"10.3324/haematol.2024.286972","DOIUrl":"https://doi.org/10.3324/haematol.2024.286972","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614726","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}