HaematologicaPub Date : 2025-07-01Epub Date: 2025-03-20DOI: 10.3324/haematol.2024.286824
Iryna Lastovytska, Silke Heidenreich, Evgeny Klyuchnikov, Christian Niederwieser, Nico Gagelmann, Johanna Richter, Radwan Massoud, Kristin Rathje, Tetiana Perekhrestenko, Gaby Zeck, Catherina Lück, Dietlinde Janson, Christine Wolschke, Francis Ayuk, Nicolaus Kröger
{"title":"Lower incidence of chronic graft-<i>versus</i>-host disease after ruxolitinib plus extracorporeal photopheresis versus ruxolitinib alone in steroid-refractory acute graft-<i>versus</i>-host disease following allogeneic stem cell transplantation.","authors":"Iryna Lastovytska, Silke Heidenreich, Evgeny Klyuchnikov, Christian Niederwieser, Nico Gagelmann, Johanna Richter, Radwan Massoud, Kristin Rathje, Tetiana Perekhrestenko, Gaby Zeck, Catherina Lück, Dietlinde Janson, Christine Wolschke, Francis Ayuk, Nicolaus Kröger","doi":"10.3324/haematol.2024.286824","DOIUrl":"10.3324/haematol.2024.286824","url":null,"abstract":"<p><p>We compared long-term outcomes in 78 patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD) treated at the University Medical Center Hamburg, Germany, between December 2015 and August 2022 who received either ruxolitinib alone (Ruxo, N=29) or Ruxo plus extracorporeal photopheresis (Ruxo-ECP, N=49). Patients were well balanced between both arms except for SR-aGvHD grade IV which was higher in the Ruxo-ECP group (45% vs. 14%, P<0.001). In both cohorts, steroids were tapered rapidly, and median steroid treatment was 39 days in Ruxo and 35 days in Ruxo-ECP. The overall response rate including complete remissions (CR) of aGvHD at day 28 was 90% and 31% for Ruxo versus 86% and 0% (P<0.001, respectively) for Ruxo-ECP. At six months, partial remission (PR) and CR status of evaluable patients was 11% and 50% in Ruxo-ECP versus 10% and 40% after Ruxo alone, respectively (P=0.018). At 12 months, PR and CR status was 6% and 17% in the Ruxo group, but 82% and 64% (P<0.001) in the Ruxo-ECP cohort, and the cumulative incidence of chronic GvHD was significantly higher after Ruxo versus Ruxo-ECP at 49% (95% CI: 33-69%) versus 24% (95% CI: 15-38%) (P=0.01). Reconstitution of B cells occurred significantly earlier at one and three months in the Ruxo arm. No difference in 1-year non-relapse mortality, relapse, and 2-year overall survival was observed. Despite the limitations of this retrospective single- center study, the data suggest a better long-term control of aGvHD and less chronic GvHD at one year combining ruxolitinib with ECP compared to ruxolitinib alone in SR-aGvHD.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1536-1544"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663439","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}
HaematologicaPub Date : 2025-07-01DOI: 10.3324/haematol.2025.287512
Francesco Rodeghiero
{"title":"Splenectomy: still a life-saving treatment in immune thrombocytopenia.","authors":"Francesco Rodeghiero","doi":"10.3324/haematol.2025.287512","DOIUrl":"https://doi.org/10.3324/haematol.2025.287512","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"27 1","pages":"1451-1453"},"PeriodicalIF":10.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521337","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}
HaematologicaPub Date : 2025-07-01Epub Date: 2025-02-06DOI: 10.3324/haematol.2024.285343
Adrian G Minson, Michael J Dickinson
{"title":"New bispecific antibodies in diffuse large B-cell lymphoma.","authors":"Adrian G Minson, Michael J Dickinson","doi":"10.3324/haematol.2024.285343","DOIUrl":"10.3324/haematol.2024.285343","url":null,"abstract":"<p><p>CD20xCD3 T-cell-engaging bispecific antibodies are a highly active new treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Epcoritamab and glofitamab have both been approved in over 30 countries as monotherapy for DLBCL after two prior treatment lines; odronextamab has recent European approval, and mosunetuzumab is active and is being developed as a combination partner. These agents can be safely combined with other immunotherapies and chemotherapy, and single-arm and randomized trial outcomes promise an expanding role for this class of drugs in earlier treatment lines. This review examines the clinical development of the CD20xCD3 bispecific antibodies in DLBCL, how the phase I and II trials inform their current use, and the key distinctions between the agents. We focus on the efficacy and safety of those bispecific antibodies most advanced in development. We also consider emerging understandings of resistance mechanisms. Finally, we review key ongoing trials and combinations and consider the potential future of bispecific antibodies within the sequence of available treatments for DLBCL.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1483-1499"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255619","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}
HaematologicaPub Date : 2025-07-01Epub Date: 2024-12-19DOI: 10.3324/haematol.2024.286331
Roberta Soscia, Giovanni Manfredi Assanto, Irene Della Starza, Riccardo Moia, Donatella Talotta, Vittorio Bellomarino, Teresa Bellissimo, Marco Antonacci, Luigi Petrucci, Gianluca Gaidano, Anna Guarini, Maurizio Martelli, Alice Di Rocco, Robin Foà, Ilaria Del Giudice
{"title":"Molecular measurable residual disease by immunoglobulin gene rearrangements on circulating tumor DNA predicts outcome in diffuse large B-cell lymphoma.","authors":"Roberta Soscia, Giovanni Manfredi Assanto, Irene Della Starza, Riccardo Moia, Donatella Talotta, Vittorio Bellomarino, Teresa Bellissimo, Marco Antonacci, Luigi Petrucci, Gianluca Gaidano, Anna Guarini, Maurizio Martelli, Alice Di Rocco, Robin Foà, Ilaria Del Giudice","doi":"10.3324/haematol.2024.286331","DOIUrl":"10.3324/haematol.2024.286331","url":null,"abstract":"<p><p>In diffuse large B-cell lymphoma (DLBCL) treatment response relies on imaging. We investigated the potential value of molecular measurable residual disease (MRD) on circulating tumor DNA (ctDNA) to predict the outcome of 73 DLBCL patients. At baseline, next-generation sequencing was used to detect clonal immunoglobulin (IG) gene rearrangements on tumor biopsies (N=57) and ctDNA (N=73). MRD monitoring was applied by tracking the IG clones in ctDNA samples collected during treatment (interim) and at the end of treatment (EOT). MRD results were correlated with clinical data and radiologic disease assessment. Before treatment, clonal IG were found in 91.2% (52/57) of tumor biopsies and in 93.2% (68/73) of ctDNA samples. In paired samples, the same clonotype was found in 69.2% (36/52) of cases. At the interim analysis, ctDNA MRD was negative in 32 of 45 evaluable patients and positive in 13 of 45, correlating significantly with progression-free survival (PFS) (78.1% MRD- vs. 30.8% MRD+; P<0.0001) after a median follow-up of 40 months. Moreover, ctDNA MRD could stratify prognosis of 27 patients in partial response (P=0.018). At EOT, ctDNA MRD was negative in 37 of 47 patients and positive in ten of 47 (PFS 83.8% MRD- vs. 0% MRD+; P<0.0001). All MRD+ patients in complete metabolic response relapsed (P<0.0001). At multivariate analysis, MRD at EOT independently predicted PFS and overall survival. Monitoring IG-based ctDNA MRD during and after treatment predicts DLBCL patients' outcome. This non-invasive method should be implemented in risk-adapted clinical trials and validated as a treatment decision-making tool.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1573-1583"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864123","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}
HaematologicaPub Date : 2025-07-01Epub Date: 2024-12-19DOI: 10.3324/haematol.2024.285826
Anna Torun, Aleksandra Zdanowicz, Nina Miazek-Zapala, Piotr Zapala, Bhaskar Pradhan, Marta Jedrzejczyk, Andrzej Ciechanowicz, Zofia Pilch, Marcin Skorzynski, Mikołaj Słabicki, Grzegorz Rymkiewicz, Joanna Barankiewicz, Claudio Martines, Luca Laurenti, Marta Struga, Magdalena Winiarska, Jakub Golab, Magdalena Kucia, Mariusz Z Ratajczak, Adam Huczynski, Dinis P Calado, Dimitar G Efremov, Abdessamad Zerrouqi, Beata Pyrzynska
{"title":"Potassium/sodium cation carriers robustly upregulate CD20 antigen by targeting MYC, and synergize with anti- CD20 immunotherapies to eliminate malignant B cells.","authors":"Anna Torun, Aleksandra Zdanowicz, Nina Miazek-Zapala, Piotr Zapala, Bhaskar Pradhan, Marta Jedrzejczyk, Andrzej Ciechanowicz, Zofia Pilch, Marcin Skorzynski, Mikołaj Słabicki, Grzegorz Rymkiewicz, Joanna Barankiewicz, Claudio Martines, Luca Laurenti, Marta Struga, Magdalena Winiarska, Jakub Golab, Magdalena Kucia, Mariusz Z Ratajczak, Adam Huczynski, Dinis P Calado, Dimitar G Efremov, Abdessamad Zerrouqi, Beata Pyrzynska","doi":"10.3324/haematol.2024.285826","DOIUrl":"10.3324/haematol.2024.285826","url":null,"abstract":"<p><p>Our investigation uncovers that nanomolar concentrations of salinomycin, monensin, nigericin, and narasin (a group of potassium/ sodium cation carriers) robustly enhance surface expression of CD20 antigen in B-cell-derived tumor cells, including primary malignant cells of chronic lymphocytic leukemia and diffuse large B-cell lymphoma. Experiments in vitro, ex vivo, and animal model reveal a novel approach of combining salinomycin or monensin with therapeutic anti-CD20 monoclonal antibodies or anti-CD20 chimeric antigen receptor T cells, significantly improving non-Hodgkin lymphoma therapy. The results of RNA sequencing, genetic editing, and chemical inhibition delineate the molecular mechanism of CD20 upregulation, at least partially, to the downregulation of MYC, the transcriptional repressor of the MS4A1 gene encoding CD20. Our findings propose the cation carriers as compounds targeting MYC oncogene, which can be combined with anti-CD20 antibodies or adoptive cellular therapies to treat non-Hodgkin lymphoma and mitigate resistance, which frequently depends on the CD20 antigen loss, offering new solutions to improve patient outcomes.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1555-1572"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864126","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}
HaematologicaPub Date : 2025-07-01Epub Date: 2024-12-19DOI: 10.3324/haematol.2024.285154
Serena De Matteis, Laura Del Coco, Federica De Castro, Anna Maria Giudetti, Beatrice Casadei, Francesco Iannotta, Francesco De Felice, Enrica Tomassini, Francesca Vaglio, Maria Naddeo, Irene Salamon, Gianluca Storci, Noemi Laprovitera, Daria Messelodi, Salvatore Nicola Bertuccio, Marta Tassoni, Barbara Sinigaglia, Francesco Barbato, Margherita Ursi, Elena Campanini, Enrico Maffini, Marcello Roberto, Cinzia Pellegrini, Elisa Dan, Chiara Pirazzini, Paolo Garagnani, Manuela Ferracin, Pier Luigi Zinzani, Francesco Paolo Fanizzi, Massimiliano Bonafè, Francesca Bonifazi
{"title":"Metabolic profile evolution in relapsed/refractory B-cell non-Hodgkin lymphoma patients treated with CD19 chimeric antigen receptor T-cell therapy and implications in clinical outcome.","authors":"Serena De Matteis, Laura Del Coco, Federica De Castro, Anna Maria Giudetti, Beatrice Casadei, Francesco Iannotta, Francesco De Felice, Enrica Tomassini, Francesca Vaglio, Maria Naddeo, Irene Salamon, Gianluca Storci, Noemi Laprovitera, Daria Messelodi, Salvatore Nicola Bertuccio, Marta Tassoni, Barbara Sinigaglia, Francesco Barbato, Margherita Ursi, Elena Campanini, Enrico Maffini, Marcello Roberto, Cinzia Pellegrini, Elisa Dan, Chiara Pirazzini, Paolo Garagnani, Manuela Ferracin, Pier Luigi Zinzani, Francesco Paolo Fanizzi, Massimiliano Bonafè, Francesca Bonifazi","doi":"10.3324/haematol.2024.285154","DOIUrl":"10.3324/haematol.2024.285154","url":null,"abstract":"<p><p>Plasma metabolomics analysis was performed on 44 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r/BNHL) infused with approved CD19 chimeric antigen receptor (CAR) T-cell products at the time of pre-lymphodepletion (PLD) and at day +1 (D1), D7, and D30 after CAR T-cell infusion. At the PLD time point, a metabolic profile characterized by high lipoproteins and lactate and low glucose contributed to poor outcome prediction in association with high lactate dehydrogenase levels. At D1, higher plasma levels of lipid metabolism products and lower glucose and glycoproteins levels were observed in tisa-cel-compared to axi-cel-treated patients. At D30, discriminant analysis found two clusters in a subgroup of patients, one with complete response lasting 1 year after therapy, and another who relapsed within 1 year (relapsed >D30). This latter showed a higher content of N-GlycA, a known biomarker of systemic inflammation that is also correlated with C-reactive protein in our case setting of relapsing patients. Our data show complex metabolomic changes that track the evolution of the disease and drug activity in the first 30 days of CAR T-cell therapy. Conceivably, a pro-inflammatory drift may be linked to a forthcoming disease relapse in CAR T patients.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1545-1554"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864120","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}
HaematologicaPub Date : 2025-07-01Epub Date: 2025-02-13DOI: 10.3324/haematol.2024.287062
Cyril Salek, Stepan Hrabovsky, Frantisek Folber, Zdenek Koristek, Jan M Horacek, Eva Fronkova, Leona Rezkova Reznickova, Pavla Pecherkova, Petr Soukup, Barbora Dluhosova, Vaclava Polivkova, Jitka Krizkova, Katerina Machova Polakova, Zuzana Vrzalova, Hana Halamova, Jan Trka, Petr Cetkovsky, Michael Doubek
{"title":"Blinatumomab in induction therapy improves molecular response in untreated adults with Ph- B-cell precursor acute lymphoblastic leukemia.","authors":"Cyril Salek, Stepan Hrabovsky, Frantisek Folber, Zdenek Koristek, Jan M Horacek, Eva Fronkova, Leona Rezkova Reznickova, Pavla Pecherkova, Petr Soukup, Barbora Dluhosova, Vaclava Polivkova, Jitka Krizkova, Katerina Machova Polakova, Zuzana Vrzalova, Hana Halamova, Jan Trka, Petr Cetkovsky, Michael Doubek","doi":"10.3324/haematol.2024.287062","DOIUrl":"10.3324/haematol.2024.287062","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1644-1648"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407144","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}
HaematologicaPub Date : 2025-07-01Epub Date: 2025-03-06DOI: 10.3324/haematol.2024.286424
Larissa Lordier, Christian A Di Buduo, Alexandre Kauskot, Nathalie Balayn, Cécile Lavenu-Bombled, Francesco Baschieri, Valérie Proulle, Cecilia P Marin Oyarzun, Francesca Careddu, Ida Biunno, Tudor Manoliu, Philippe Rameau, Isabelle Plo, Nicolas Papadopoulos, Stefan Constantinescu, William Vainchenker, Guillaume Nam Nguyen, Paola Ballerini, Remi Favier, Alessandra Balduini, Hana Raslova
{"title":"Increased RhoA pathway activation downstream of αIIbβ3/SRC contributes to heterozygous Bernard Soulier syndrome.","authors":"Larissa Lordier, Christian A Di Buduo, Alexandre Kauskot, Nathalie Balayn, Cécile Lavenu-Bombled, Francesco Baschieri, Valérie Proulle, Cecilia P Marin Oyarzun, Francesca Careddu, Ida Biunno, Tudor Manoliu, Philippe Rameau, Isabelle Plo, Nicolas Papadopoulos, Stefan Constantinescu, William Vainchenker, Guillaume Nam Nguyen, Paola Ballerini, Remi Favier, Alessandra Balduini, Hana Raslova","doi":"10.3324/haematol.2024.286424","DOIUrl":"10.3324/haematol.2024.286424","url":null,"abstract":"<p><p>Bernard Soulier syndrome (BSS) is a severe bleeding disorder with moderate to severe thrombocytopenia, giant platelets, and platelet dysfunction, caused by biallelic mutations in GP1BA, GP1BB, or GP9 genes. We generated induced pluripotent stem cells (iPSC) from a BSS patient with a novel heterozygous GP1BA p.N103D mutation, resulting in moderate macrothrombocytopenia. The mutation does not affect megakaryocyte (MK) differentiation or GPIb-GPIX complex expression but reduces affinity to von Willebrand factor (VWF). It induces increased signaling independent of VWF and αIIbβ3-mediated outside-in signaling, causing a profound defect in proplatelet formation after adhesion on fibrinogen. Pre-activation of αIIbβ3 integrin and heightened stress fiber formation linked to RhoA pathway overactivation were observed, likely due to increased phosphorylation of SRC at Y419 downstream of GPIbα. Dasatinib, a SRC inhibitor, restored stress fiber formation. Using a 3D bone marrow model to mimic platelet release under flow, we demonstrated that the ROCK1/2 inhibitor Y27632 increased platelet number and restored platelet size in GPIbαN103D MK, as well as in MK from two other patients with heterozygous GP1BA mutations (p.L160P and p.N150S). However, Y27632 had no additional effect on platelet generation from MK of two patients with biallelic BSS, suggesting a distinct molecular mechanism in biallelic cases.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1596-1609"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566566","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}
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