British Journal of Haematology最新文献

{"title":"Editor's Note to the letter ‘Therapeutic potential of the latest oxygen affinity modifying agent, GBT021601, for treating sickle cell disease is questionable’ by Drs. Eaton, Alaimo, Metaferia, Cellmer, Thein and Bunn","authors":"Peter Hokland","doi":"10.1111/bjh.19865","DOIUrl":"10.1111/bjh.19865","url":null,"abstract":"","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"205 6","pages":"2530"},"PeriodicalIF":5.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relevance of the E756del common variant in the PIEZO1 gene for haemolytic anaemia and hepatic iron overload.","authors":"Federica Maria Esposito, Vanessa D'Onofrio, Barbara Eleni Rosato, Roberta Marra, Antonella Nostroso, Anthony Iscaro, Mariangela Manno, Michela Ribersani, Virginia Giorgi, Renata Celia, Carmelo Piscopo, Achille Iolascon, Roberta Russo, Immacolata Andolfo","doi":"10.1111/bjh.19886","DOIUrl":"10.1111/bjh.19886","url":null,"abstract":"","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of the latest oxygen affinity-modifying agent, GBT021601, for treating sickle cell disease is questionable","authors":"Braydon Alaimo, Belhu Metaferia, Troy Cellmer, Swee Lay Thein, H. Franklin Bunn, William A. Eaton","doi":"10.1111/bjh.19697","DOIUrl":"10.1111/bjh.19697","url":null,"abstract":"<p>We think it is important that readers of the British Journal of Haematology should be aware of several important aspects of the latest oxygen-modifying drug, GBT021601, for treating sickle cell disease (SCD) published last year in your journal by Dufu et al.<span><sup>1</sup></span> Treating SCD by modifying oxygen affinity is a complex strategy owing to many subtle aspects of sickle haemoglobin (haemoglobin S [HbS]) biochemistry, physiology and kinetics that must be considered.<span><sup>2</sup></span> To make our discussion of this subject more easily understandable, we first provide some important background information.</p><p>Haemoglobin has two arrangements of its four subunits, 2α and 2β, that are in rapidly reversible equilibrium.<span><sup>3</sup></span> One, called <b>T</b> to represent the tension provided by inter-subunit salt-bridges, has a low affinity for oxygen and has the conformation of fully deoxygenated haemoglobin and the other, called <b>R</b> for relaxed (no inter-subunit salt bridges), has a high affinity for oxygen and has the conformation of fully oxygenated haemoglobin.<span><sup>3</sup></span> As haemoglobin is deoxygenated in the tissues, the shift in the equilibrium population from <b>R</b> to <b>T</b> gives rise to the characteristic sigmoid shape of the oxygen dissociation curve (ODC) that facilitates binding of oxygen in the lungs and unloading it in the tissues. In the case of HbS, deoxygenation results in the formation of fibres that stiffen and distort (‘sickle’) red blood cells (RBC's), the root cause of vaso-occlusion and its consequent pathology in SCD.<span><sup>4</sup></span></p><p>Experiments showed that only the <b>T</b> conformation polymerizes and that two different tertiary conformations (<b><i>t</i></b> and <b><i>r</i></b>) within <b>T</b> also play a role.<span><sup>5</sup></span> These experiments, as well as early studies by Beutler,<span><sup>6</sup></span> led to the concept that binding a drug to shift the conformational equilibrium towards non-polymerizing <b>R</b> would reduce sickling and therefore be a viable strategy for drug treatment of SCD. This approach resulted in many attempts to develop a drug that binds preferentially to <b>R</b>. Voxelotor (GBT440, oxybryta) is the only one so far approved by the FDA that acts by this mechanism. There was no evidence that voxelotor decreases sickle cell crisis frequency, which is of utmost important to the patient. However, crisis frequency was not an end-point in FDA's consideration, which approved the drug because of the increase in haemoglobin levels.</p><p>The reason that treatment with voxelotor is controversial is that the reduction in sickling is counteracted by the higher oxygen affinity, which compromises oxygen unloading in the tissues in SCD.<span><sup>2, 7, 8</sup></span> In our 2021 <i>Blood</i> article,<span><sup>9</sup></span> we provided a theoretical answer to the question of how much oxygen is delivered when cells from patients","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"205 6","pages":"2527-2529"},"PeriodicalIF":5.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of fitness for bleomycin use and management of bleomycin pulmonary toxicity in patients with classical Hodgkin lymphoma: A British Society for Haematology Good Practice Paper.","authors":"Aisling Barrett, Nimish Shah, Andrew Chadwick, David Burns, Cathy Burton, David J Cutter, George A Follows, Pam McKay, Wendy Osborne, Elizabeth Phillips, Matthew R Wilson, Graham P Collins","doi":"10.1111/bjh.19840","DOIUrl":"10.1111/bjh.19840","url":null,"abstract":"<p><p>This good practice paper (GPP) is intended to support clinicians in assessing patient fitness for bleomycin and in management of bleomycin pulmonary toxicity (BPT) where it occurs. Bleomycin, originally developed as an antibiotic in the 1960s, has been a cornerstone of therapy for classical Hodgkin lymphoma (CHL) since results of its use in combination with doxorubicin, vincristine and dacarbazine (ABVD) were first published by Bonadonna et al in 1975 1. The same author recognised high rates of respiratory morbidity in these patients 2, and bleomycin-;related pulmonary toxicity (BPT) is now a well-;recognised and feared complication with its use. ABVD and BEACOPP/ BEACOPDac (bleomycin, cyclophosphamide, etoposide, doxorubicin, vincristine and prednisolone, with procarbazine or dacarbazine) are standard first-;line treatments in CHL patients, but considerable variation remains in assessing patient fitness for bleomycin both clinically and with respiratory investigations. A recent survey of British haematologists regularly using bleomycin revealed that 87.5% have no local protocols for assessing patients in an evidence-;based fashion, with wide variations in practice captured in the same survey (personal data). A working group was established and a literature review undertaken with the goal of presenting practical recommendations for clinicians regarding bleomycin use based on available evidence and expert opinion.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Needle-like red cell inclusions in congenital erythropoietic porphyria.","authors":"Ana Mendoza, María Gema Crespo, Marta Morado","doi":"10.1111/bjh.19875","DOIUrl":"10.1111/bjh.19875","url":null,"abstract":"","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memantine treatment in sickle cell disease: A 1-year study of its effects on cognitive functions and neural processing.","authors":"Sivan Raz, Ariel Koren, Anna Yu Bogdanova, Max Gassmann, Carina Levin","doi":"10.1111/bjh.19866","DOIUrl":"https://doi.org/10.1111/bjh.19866","url":null,"abstract":"<p><p>This study evaluates the neurocognitive and electrophysiological effects of 1-year memantine treatment in 14 adolescents and young adults (mean age 24 years) with sickle cell disease (SCD, incluing sickle cell anaemia and sickle cell β-thalassemia), hypothesizing improvements in cognitive functions and neural processing. Participants underwent assessments using subtests from the Wechsler Intelligence Scale and a computerized task-switching paradigm with concurrent event-related potential (ERP) recordings, both before and after the treatment period. Assessments focused on processing speed, working memory, attention and executive function. ERP measurements targeted brain response changes during task switching. Memantine treatment enhanced cognitive test performance, especially in processing speed as shown by the Digit-Symbol Coding and Symbol-Search tests. Results indicated improved visuospatial and graphomotor speed, working memory and attention. The task-switching test revealed reduced error rates, suggesting decreased cognitive load and enhanced executive control. Electrophysiological changes in P1 and P3 amplitudes at frontal and parietal locations post-treatment pointed to more efficient neural processing in tasks requiring cognitive flexibility. These preliminary findings from a Phase II clinical study serve as a 'proof of concept', exploring the feasibility and potential effectiveness of memantine treatment in SCD-a previously uninvestigated context. They support the rationale for more extensive investigations to confirm these results and assess memantine's broader effectiveness.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Checkpoint inhibition in macroglobulinaemia","authors":"Prashant Kapoor","doi":"10.1111/bjh.19844","DOIUrl":"10.1111/bjh.19844","url":null,"abstract":"<p>Waldenström macroglobulinaemia (WM) is a unique, cluster of differentiation (CD) 20+ B-cell malignancy, with a characteristic immunoglobulin M-secreting lymphoplasmacytic bone marrow infiltrate that is bolstered by a highly supportive microenvironment, including upregulated programmed death 1 expression. However, the impact of checkpoint inhibition in WM is unclear.</p><p>Commentary on: Kothari et al. PembroWM: A phase II trial to investigate the safety and efficacy of rituximab and pembrolizumab in relapsed/refractory Waldenström's macroglobulinaemia. Br J Haematol 2024; 205:2273-2281.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"205 6","pages":"2128-2130"},"PeriodicalIF":5.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19844","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of clonal haematopoiesis with recurrent venous thromboembolism: A case-control study.","authors":"Cornelia Englisch, Rafaela Vostatek, Theresa Schramm, Christoph J Binder, Ingrid Pabinger, Roland Jäger, Cihan Ay","doi":"10.1111/bjh.19871","DOIUrl":"https://doi.org/10.1111/bjh.19871","url":null,"abstract":"<p><p>Venous thromboembolism (VTE) is the third most common cardiovascular disease. Clonal haematopoiesis (CH) is linked to cardiovascular disease risk, but its potential association with VTE remains poorly understood. We assessed the prevalence of CH in patients with recurrent VTE (n = 107; median age [IQR] 57 [48-63] years, 44.9% female) and matched healthy controls (n = 127; median age [IQR] 53 [45-60] years, 51.2% female) to investigate a putative association of CH with VTE risk. We detected 12 CH-associated mutations in 11 (10.3%) VTE cases and six mutations in 5 (3.9%) controls. Thus, patients with recurrent VTE tended to have higher odds of presenting with CH compared to controls (OR: 2.74, 95% CI: 0.95-9.16). Moreover, the odds of detecting CH were significantly higher in VTE cases in the subgroup of individuals without thrombophilia (OR: 4.58, 95% CI: 1.48-15.99). VTE cases with CH showed elevated platelet counts compared to cases and controls without CH (median [IQR]: 292 [254-298], 223 [198-260] and 220 [185-259] × 10⁹/L; both p < 0.01). Fibrinogen, sP-selectin, D-dimer and hsCRP levels did not differ according to CH status. Overall, we identified a trend for an association between CH and recurrent VTE, particularly in individuals without underlying thrombophilia, warranting further research in this patient group.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of plasma proteomics in patients with immune thrombocytopenia.","authors":"Rick Kapur","doi":"10.1111/bjh.19882","DOIUrl":"https://doi.org/10.1111/bjh.19882","url":null,"abstract":"<p><p>ITP is an acquired autoimmune bleeding disorder characterized by an isolated thrombocytopenia. The pathophysiology is highly multifactorial and involves antibody- and/or cytotoxic T cell-mediated killing of platelets and disruption of megakaryocyte function hampering platelet production. ITP remains a diagnosis of exclusion, and due to the high degree of variability between patients, it remains challenging to predict disease courses and responses to therapeutic agents. Hence, diagnostic and therapeutic laboratory biomarkers are highly warranted. To address this issue, in their paper, Jiang and colleagues have performed plasma proteomics in ITP patients (n = 40), in comparison to patients with thrombocytopenia due to other causes than ITP (non-ITP thrombocytopenia, n = 19) and healthy controls (n = 18). The data underscore that patients with ITP have a distinct plasma proteomic signature compared to non-ITP thrombocytopenia patients and healthy individuals. The findings should be further validated and investigated but suggest that the application of plasma proteomics is feasible and promising with respect to the search for potential biomarkers in patients with ITP. Commentary on: Jiang et al. Targeted proteomics profiling reveals valuable biomarkers in the diagnosis of primary immune thrombocytopenia. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19760.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sickle cell disease in India: Not just a mild condition.","authors":"Manpreet Kochhar, Patrick T McGann","doi":"10.1111/bjh.19877","DOIUrl":"https://doi.org/10.1111/bjh.19877","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a common and life-threatening global health problem, with more than 500 000 affected infants born annually. The burden of SCD in sub-Saharan Africa is well established, but the comparably high prevalence in India is not well recognized and many consider SCD in India to be less severe. In their paper, a national study in India demonstrated the significant impact of SCD for patients, families and the healthcare system, supporting a call to action to recognize and address SCD as a serious and common health condition in India. Commentary on: Seth et al. Burden of vaso-occlusive crisis, its management, and impact on quality of life of Indian sickle cell disease patients. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19829.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}