Haematologica最新文献

{"title":"Optimization of T-cell-replete haploidentical hematopoietic stem cell transplantation: the Chinese experience.","authors":"Xiaodong Mo, Xuying Pei, Xiaojun Huang","doi":"10.3324/haematol.2024.286194","DOIUrl":"10.3324/haematol.2024.286194","url":null,"abstract":"<p><p>Haploidentical-related donor (HID) hematopoietic stem cell transplantation (HSCT) has undergone significant advances in recent decades. Granulocyte colony-stimulating factor- and antithymocyte globulin-based protocols and post-transplantation cyclophosphamide-based regimens represent two of the current T-cell-replete protocols in HID HSCT. Recently, the optimization of several critical transplant techniques has further improved hematopoietic reconstitution, decreased the incidence of relapse and graft-versus-host disease after HID HSCT, and extended the application of HID HSCT to older patients and those with non-malignant hematologic disorders. Combining this approach with novel immunotherapy could further improve the efficacy and safety of HID HSCT. This review focuses on recent progress in the optimization of HID HSCT.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"562-575"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681536","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}

{"title":"Challenges associated with access to recently developed hemophilia treatments in routine care: perspectives of healthcare professionals.","authors":"Karin Berger, Roxy H O'Rourke, Matteo Nicola Dario Di Minno, Angelika Batorova, Kaan Kavakli, Pier Mannuccio Mannucci, Wolfgang Schramm, Rhonda L Bohn, Louis Aledort","doi":"10.3324/haematol.2024.285647","DOIUrl":"10.3324/haematol.2024.285647","url":null,"abstract":"<p><p>The treatment landscape for hemophilia continues to rapidly develop, and expectations for future treatment success are high. There is limited information on the challenges of accessing new and innovative therapies. The aim of this study was to explore challenges of accessing hemophilia treatment from the perspective of healthcare professionals (HCP). A cross-sectional study design was used. A pilot-tested, online survey was distributed to hemophilia treatment centers in Australia, Canada, France, Italy, New Zealand, Republic of Ireland, Turkey, USA and UK. The questionnaire covered questions on product access, economic considerations, health technology assessment requirements, and patient organization involvement. The results were analyzed descriptively using SPSS. A total of 154 HCP completed the questionnaire. There was heterogeneity across countries, regions, and centers regarding HCP knowledge of access to novel recently developed treatments. Notable limitations to access were reported such as differences in access based on age of patient and type of product, economic considerations, and the growing influence of health technology assessment bodies. Many countries have a hemophilia patient organization that does not have a vote at the decision-making table. There is a need to empower HCP to better understand national healthcare structures and decisions that lead to access limitations. Requirements from health technology assessment bodies must be understood to optimally design clinical studies and value generation of treatment options. This may strengthen the hemophilia treatment center's voice to collectively mandate for exchange with key involved individuals, such as the payers and politicians for the provision of optimal therapy.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"673-682"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619066","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}

{"title":"Loncastuximab in high-risk and heavily pretreated relapsed/refractory diffuse large B-cell lymphoma: a realworld analysis from 21 US centers.","authors":"Viktoriya Zelikson, Ashwath Gurumurthi, Yazeed Sawalha, Kaitlin Annunzio, Aditi Saha, Ning Dong, David Qualls, Behzad Amoozgar, Brad Kahl, John Baird, Pavan Challa, Scott F Huntington, Jennifer Santos, Steven Bair, Mayur Narkhede, Shuning Li, Zachary Frosch, Carrie Ho, Stephen D Smith, Allison Winter, Daniel Landsburg, Fateeha Furqan, Mehdi Hamadani, Katelin Baird, Jason Romancik, Hanan Alharthy, Jennie Law, Leyla Bojanini, Ranjana Advani, Boyu Hu, Patrick Connor Johnson, Natalie S Grover, Mwanasha Merril, Jennifer L Crombie, Nazila Shafagati, Cole Sterling, Loretta J Nastoupil, Narendranath Epperla, Emily C Ayers","doi":"10.3324/haematol.2024.285977","DOIUrl":"10.3324/haematol.2024.285977","url":null,"abstract":"<p><p>Outcomes in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are poor. Loncastuximab- teserine (Lonca) is an antibody-drug conjugate which was approved by the Food and Drug Administration for the treatment of patients with R/R DLBCL who have received at least two prior lines of therapy, based on the results of the LOTIS-2 trial. However, there are limited data regarding its efficacy in the real-world setting. This retrospective study included 21 US centers and evaluated outcomes of patients with R/R DLBCL treated with Lonca. Our analysis comprises 187 patients with notably higher-risk baseline features compared to those of the LOTIS-2 population, including a higher proportion of patients with bulky disease (17% vs. 0%), high-grade B-cell histology (22% vs. 8%), and increased number of prior lines of therapy (median 4 vs. 3). The complete response rate was 14% and overall response rate was 32%. The median event-free survival and overall survival were 2.1 and 4.6 months, respectively. Those with bulky disease and high-grade B-cell histology had significantly worse outcomes, and those with non-germinal center cell of origin and a complete response to the most recent line of therapy demonstrated superior outcomes. In summary, in this largest retrospective cohort study of Lonca in the real-world setting, the response rates, event-free survival and overall survival were lower than those reported in LOTIS-2, which is likely reflective of its use in higher risk and more heavily pre-treated patients in the real world compared to the patients enrolled on a clinical study.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"706-714"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619079","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}

{"title":"von Willebrand disease and angiodysplasia: a wider view of pathogenesis in pursuit of therapy.","authors":"Christina Crossette-Thambiah, Anna M Randi, Michael Laffan","doi":"10.3324/haematol.2024.285244","DOIUrl":"10.3324/haematol.2024.285244","url":null,"abstract":"<p><p>Bleeding in the gastrointestinal tract in patients with von Willebrand disease continues to pose a therapeutic challenge for clinicians. It is associated with significant morbidity and mortality and represents the major unmet need in this disease. Defective angiogenesis in the gut is primarily responsible, resulting in angiodysplastic malformations making bleeding notoriously refractory to standard replacement therapy. A substantial body of evidence now shows that von Willebrand factor has a role in the regulation of angiogenesis but the mechanisms responsible for the formation of vascular malformations remain incompletely understood. Data from the wider field of vascular malformations may lend insight and point to novel therapeutic approaches. Here we review evidence linking von Willebrand factor to angiodysplasia, the associated molecular mechanisms and the implications for therapy.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"588-595"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590151","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}

{"title":"Targeting P-selectin and interleukin-1β in mice with sickle cell disease: effects on vaso-occlusion, liver injury and organ iron deposition.","authors":"Érica M F Gotardo, Lidiane S Torres, Bruna Cunha Zaidan, Lucas F S Gushiken, Pâmela L Brito, Flavia C Leonardo, Claudia H Pellizzon, John Millholland, Sergei Agoulnik, Jiri Kovarik, Fernando F Costa, Nicola Conran","doi":"10.3324/haematol.2024.286418","DOIUrl":"10.3324/haematol.2024.286418","url":null,"abstract":"<p><p>Continuous vaso-occlusive and inflammatory processes cause extensive end-organ damage in adults with sickle cell disease (SCD), and there is little evidence that long-term hydroxyurea therapy prevents this. In initial trials, P-selectin blockade with crizanlizumab reduced SCD vaso-occlusive crisis frequency, and interleukin (IL)-1β inhibition in SCD patients, using canakinumab, lowered inflammatory markers. We used murine SCD models to examine the effects of acute and chronic blockade of P-selectin and of IL-1β on vaso-occlusive events, their inflammatory profile and organ health. Both approaches improved impaired cutaneous microvascular perfusion in SCD mice by reducing TNF-α-induced vaso-occlusion. Acute P-selectin blockade markedly reduced TNF-α-induced neutrophil-platelet aggregate formation in SCD mice, and decreased leukocyte- rolling movements in the microvasculature, while acute IL-1β inhibition attenuated microvascular leukocyte adhesion. Six weeks of IL-1β-blocking immunotherapy improved the inflammatory profile of SCD mice, considerably reduced hepatic fibrosis and provided some relief from lung injury. In contrast, although P-selectin blockade reduced glomerular congestion, no significant benefit to overall organ pathology was observed. Unexpectedly, while combining the two immunotherapies reduced microvascular occlusion, their prolonged use caused acute liver injury. Notably, inhibition of IL-1β, but not of P-selectin, remarkably decreased hemosiderosis, in association with reduced tissue macrophage infiltration and the correction of biomarkers of dysregulated iron turnover. Our findings suggest that the attenuation of inflammation, as well as of vaso- occlusive processes, may be crucial for mitigating organ damage in SCD. Future trials should explore the ability of cytokine blockade to prevent multi-organ damage in patients with SCD, beyond evaluating vaso-occlusive crisis frequency.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"725-738"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681690","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}

{"title":"Ultrasound-mediated catheter delivery of tissue plasminogen activator promotes thrombolysis by altering fibrin fiber thickness and clot permeability.","authors":"Robert A S Ariëns, Andrew S P Sharp, Cédric Duval","doi":"10.3324/haematol.2024.286684","DOIUrl":"10.3324/haematol.2024.286684","url":null,"abstract":"<p><p>It has been proposed that low power, high frequency ultrasound can augment the ability of thrombolytic agents to dissolve clot in patients with venous thromboembolism. We created a bench model to examine what role and mechanism ultrasound may have in this process. Fibrin polymerization was analyzed through modified light-scattering experiments with the inclusion of catheter-mediated ultrasound application. We studied fibrin fiber diameters through scanning electron microscopy of ultrasound treated fibrin clots. Clot porosity was investigated using permeation tests, while fibrinolysis was analyzed through light-scattering experiments, and by changes in porosity of lysing clots under flow. Whilst application of ultrasound did not change initial fibrin polymerization, it did induce a reversible change in maximal turbidity of already formed fibrin clots. This change in turbidity was caused by a reduction in fibrin fiber diameter and was associated with an increase in clot porosity. These reversible structural changes were associated with a linear increase in fibrinolysis rates under static conditions, while an exponential increase in rates was observed under flow. The use of ultrasound augmentation of thrombolysis enhances clot dissolution through greater and more rapid fibrin degradation. This is due to conformational change created by the ultrasound in clot structure, a reversible phenomenon that may increase binding sites for lytic agent, and could potentially allow the use of lower doses and shorter infusion times of ultrasound-assisted thrombolytic to treat venous thromboembolism in vivo.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"665-672"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681708","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}

{"title":"Comparative efficacy of lisocabtagene maraleucel in the PILOT study <i>versus</i> second-line chemotherapy regimens in the real world.","authors":"Nilanjan Ghosh, Alison Sehgal, Fei Fei Liu, Ana Kostic, Alessandro Crotta, Marc De Benedetti, Jillian Faccone, Lily Peng, Leo I Gordon","doi":"10.3324/haematol.2024.285828","DOIUrl":"10.3324/haematol.2024.285828","url":null,"abstract":"<p><p>This study assessed the comparative efficacy of lisocabtagene maraleucel (liso-cel) in the open-label, phase II PILOT study (clinicaltrials.gov NCT03483103) versus conventional second-line (2L) chemotherapy regimens in the real world administered to patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who were not intended for hematopoietic stem cell transplantation (HSCT). The liso-cel-treated cohort (N=61) was based on patients who received liso-cel in the PILOT study. The conventional chemotherapy cohort included patients who met PILOT eligibility criteria and received conventional 2L chemotherapy in the real-world clinical setting (N=273). After using the trimmed stabilized inverse probability of treatment weighting method to balance cohorts according to baseline characteristics, there were statistically significant differences in all tested measures of efficacy. Compared with real-world conventional chemotherapy regimens, liso-cel demonstrated higher overall response rates (79.6% with liso-cel vs. 50.5% with conventional chemotherapy; relative risk [RR]: 1.6; P<0.0001) and complete response rates (53.1% vs. 24.0%; RR: 2.2; P<0.0001), longer median duration of response (12.1 vs. 4.3 months; hazard ratio [HR: 0.40; P=0.0001), longer median event-free survival (7.0 vs. 2.8 months; HR: 0.43; P<0.0001), longer median progression-free survival (7.0 vs. 2.9 months; HR: 0.46; P<0.0001), and longer median overall survival (not reached vs. 12.6 months; HR: 0.58; P=0.0256). Results from analyses applying various additional statistical approaches consistently favored outcomes with liso-cel over real-world conventional chemotherapy regimens. These results reinforce the efficacy of liso-cel as 2L therapy for patients with R/R LBCL who are not intended for HSCT.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"693-705"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545069","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}

{"title":"Clinical outcomes of three haploidentical transplantation protocols for hematologic malignancies based on data from the Chinese Bone Marrow Transplantation Registry Group.","authors":"Zheng-Li Xu, Jie Ji, San-Bin Wang, Nai-Nong Li, Jian Zhou, Ming-Hao Lin, Lan-Ping Xu, Yu Wang, Xiao-Hui Zhang, Xiao-Jun Huang","doi":"10.3324/haematol.2024.286040","DOIUrl":"10.3324/haematol.2024.286040","url":null,"abstract":"<p><p>This study aimed to demonstrate the clinical outcomes of granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG), posttransplantation cyclophosphamide (PTCy) and PTCy combined with low-dose ATG (PTCy with ATGlow)-based haploidentical transplantation protocols in patients with hematologic malignancies. The comparisons were conducted via propensity score matching (PSM) analysis to balance the basic characteristics among different groups and were based on the transplantation data reported to the Chinese Bone Marrow Transplantation Registry Group (CBMTRG) from January 2020 to December 2022. For each patient in the PTCy or PTCy with ATGlow group, patients (at a 1:2 ratio) from the G-CSF/ATG group were selected. In total, the PTCy group (N=122) was matched with the G-CSF/ATG group 1 (N=230), and the PTCy+ATGlow group (N=123) was matched with the G-CSF/ATG group 2 (N=226). Compared with those in the PTCy group, the incidences of 28- day neutrophil engraftment (P=0.005), 100-day platelet engraftment (P=0.002), median time to neutrophil engraftment (P<0.001) and platelet engraftment (P=0.011) were significantly greater in the G-CSF/ATG group. No significant differences were observed in acute graft-versus-host disease (aGVHD) incidence or relapse incidence. In addition, patients in the G-CSF/ ATG group had lower non-relapse mortality (NRM; P<0.001), better 3-year overall survival (OS; P<0.001) and leukemia-free survival (P<0.001) rates than those in the PTCy group. Similarly, the G-CSF/ATG group achieved lower NRM (P<0.001) and better 3-year leukemia-free survival (P=0.002) than the PTCy+ATGlow group. In conclusion, G-CSF/ATG-based haplo-HSCT may be a preferential choice for the Chinese population with hematologic malignancies. In the future, a randomized controlled study is needed for further confirmation.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"629-639"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371704","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}

{"title":"Comparison of EasyM, a clonotypic mass spectrometry assay, and EuroFlow minimal residual disease assessment in multiple myeloma.","authors":"Jessie Zhao, Tiffany Khong, Malgorzata Gorniak, Abir Khaled, Zac McDonald, John Reynolds, Sridurga Mithraprabhu, Nicholas Bingham, Suehli Lim, Daniel Wong, Anna Johnston, Olga Motorna, Nicholas Murphy, Hang Quach, Liqiang Yang, Andrew Spencer","doi":"10.3324/haematol.2024.285933","DOIUrl":"10.3324/haematol.2024.285933","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"764-767"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589910","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}

{"title":"Temporal changes in erythroid progenitors in critically ill patients: a prospective cohort study.","authors":"Caroline Scott, Isabella Dale-Harris, Andrew E Armitage, Alexandra E Preston, Simon J Stanworth, Timothy James, Stuart R McKechnie, Peter A Robbins, Hal Drakesmith, Noemi B A Roy, Akshay Shah","doi":"10.3324/haematol.2024.285530","DOIUrl":"10.3324/haematol.2024.285530","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"739-743"},"PeriodicalIF":8.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371726","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}