EJHaem最新文献

{"title":"Clinical significance of Philadelphia-like-related genes in a resource-constrained setting of adult B-acute lymphoblastic leukemia patients","authors":"Keli Lima, César Alexander Ortiz Rojas, Frederico Lisboa Nogueira, Wellington Fernandes da Silva, Rita de Cássia Cavaglieri, Luciana Nardinelli, Aline de Medeiros Leal, Elvira Deolinda Rodrigues Pereira Velloso, Israel Bendit, Alvaro Alencar, Charles G. Mullighan, João Agostinho Machado-Neto, Eduardo Magalhães Rego","doi":"10.1002/jha2.1030","DOIUrl":"10.1002/jha2.1030","url":null,"abstract":"<p>Dear Editor,</p><p>The t(9;22)(q34;q11) translocation, which produces <i>BCR::ABL1</i> (Ph<sup>+</sup>), a constitutively active tyrosine kinase, occurs in approximately 25% of adult patients with acute lymphoblastic leukemia (ALL). Before the advent of tyrosine kinase inhibitors (TKIs), this molecular subtype was associated with unfavorable clinical outcomes [<span>1, 2</span>]. The incorporation of TKIs resulted in significant improvements in overall survival (OS), event-free survival (EFS), and rates of complete remission (CR). For example, the addition of the TKI dasatinib to chemotherapy resulted in higher rates of complete molecular response (CMR) and lower rates of relapse compared to chemotherapy alone [<span>3</span>].</p><p>In 2016, the World Health Organization recognized a new provisional diagnostic entity called “Philadelphia-like” (Ph-like) or “<i>BCR::ABL1</i>-like” ALL, which refers to a subtype of the B-ALL precursor that, despite presenting a gene signature and molecularly similar to Ph<sup>+</sup> ALL, does not present the BCR::ABL1 fusion protein [<span>4-6</span>]. This group of patients exhibits poor clinical outcomes and presents multiple rearrangements, mutations, and copy number variations involving kinase or cytokine receptor genes, which lead to the activation of JAK2/STAT, ABL1, and RAS signaling pathways [<span>7</span>]. Although several clinical trials have investigated the efficacy of JAK- or ABL-directed TKIs in Ph-like ALL, the standard of care is still to be determined.</p><p>The identification of patients with Ph-like ALL remains challenging in clinical practice, as methodologies that comprehensively evaluate gene expression are required. In this regard, Chiaretti et al. [<span>8</span>] proposed a tool based on the expression of 10 genes by quantitative polymerase chain reaction (qPCR) and a statistical model (10-gene score) for screening patients with Ph-like ALL.</p><p>In the present study, we investigated the expression of Ph-like-related genes [<span>8</span>] in samples from healthy donors (<i>n</i> = 12) and adult patients with B-ALL (<i>n</i> = 83 [Ph<sup>+</sup> <i>n</i> = 33 and Ph<sup>−</sup> <i>n</i> = 50]) and their association with clinical and laboratory characteristics and survival outcomes. The research protocol was approved by the Committee of Ethics in Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo (CAAE: 32409120.0.0000.0068). An overview of patient characteristics is provided in Table S1. Briefly, those patients were treated according to their Philadelphia status and age, regimens were described elsewhere [<span>9</span>]. Total RNA was extracted from bone marrow mononuclear cell samples, with subsequent complementary DNA (cDNA) synthesis from 1 µg of RNA accomplished using the High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific). qPCR analysis was executed on a QuantStudio 3 Real-Time PCR System, employing a SybrGreen System (Thermo Fi","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1366-1369"},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VEXAS without vacuoles: Linking genotype to phenotype","authors":"Sara Zhukovsky,&nbsp;Anton Rets,&nbsp;Tawnie Braaten,&nbsp;Ami B. Patel","doi":"10.1002/jha2.1016","DOIUrl":"https://doi.org/10.1002/jha2.1016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>VEXAS syndrome is a rare condition characterized by somatic mutations in the ubiquitin-like modifier activating enzyme 1 (<i>UBA1</i>) gene and a constellation of clinical/morphologic findings, including the presence of cytoplasmic vacuoles within bone marrow hematopoietic cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and objectives</h3>\u0000 \u0000 <p>In this report, we present a case of a male patient diagnosed with VEXAS-associated myelodysplastic syndrome following the detection of a non-canonical <i>UBA1</i> p.Gly477Ala variant whose bone marrow biopsy revealed a conspicuous absence of cytoplasmic vacuolization in hematopoietic cells. This case prompts a comprehensive review of the existing literature on the significance and pathobiology of vacuolization in the context of VEXAS and <i>UBA1</i> mutations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"981-986"},"PeriodicalIF":0.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central nervous system relapse of an extranodal natural killer/T-cell lymphoma","authors":"Radu Chiriac,&nbsp;Lucile Baseggio,&nbsp;Camille Golfier","doi":"10.1002/jha2.1025","DOIUrl":"https://doi.org/10.1002/jha2.1025","url":null,"abstract":"&lt;p&gt;A man in his 50s presented with rapid neurological decline and sudden onset of facial diplegia, occurring six months after receiving intensified therapy with autologous stem cell transplantation for stage IV extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL), which had been diagnosed 1 year earlier. Central nervous system (CNS) prophylaxis with high-dose methotrexate (HD-MTX) was initially administered.&lt;/p&gt;&lt;p&gt;On admission, blood work revealed no circulating lymphoma cells. Plasma Epstein–Barr virus DNA concentration was 830,000 copies/mL (reference range: 180–500 copies/mL). Brain and spine magnetic resonance imaging (MRIs) were normal. A lumbar puncture revealed a cerebrospinal fluid (CSF) cytospin preparation with monomorphic medium to large lymphomatous cells exhibiting irregular nuclear contours and variably condensed chromatin, along with scant to moderate cytoplasm containing azurophilic granules (Figure 1A). Flow cytometry of the CSF confirmed an aberrant NK/T-cell phenotype: CD3-, CD5-, CD2+, CD7+, CD57+, and CD45RO+ (Figure 1B). Next-generation sequencing of the CSF revealed mutations in &lt;i&gt;BCOR&lt;/i&gt; (VAF 74%), &lt;i&gt;TP53&lt;/i&gt; (VAF 76%), &lt;i&gt;DDX3X&lt;/i&gt; (VAF 63%), and &lt;i&gt;JAK3&lt;/i&gt; (VAF 34%), the same mutations as in the initial biopsy. A CNS leptomeningeal relapse of known ENKTCL was confirmed. Pembrolizumab and HD-MTX were subsequently initiated, resulting in symptom regression.&lt;/p&gt;&lt;p&gt;After the second cycle, the patient presented with fatigue, muscle weakness, mood changes, and decreased vision associated with difficulty reading. There was a complete resolution of the initially described facial paralysis, and no lymphoma involvement was noted. Brain MRI revealed bilateral fronto-parietal subdural detachment (Figure 1C, asterisk) suggestive of a subacute subdural hematoma, along with thickening of the pituitary gland (20 mm in width and 14 mm in height) (Figure 1D, asterisk) and nodular thickening of the pituitary stalk (6 mm) (Figure 1E, asterisk). Homogeneous enhancement of the pituitary gland and stalk after gadolinium injection indicated hypophysitis, with the pituitary stalk exerting a mass effect on the optic chiasm. No diffusion-weighted hyperintensity of the pituitary gland was observed. Deficiencies in adrenocorticotropic and thyroid-stimulating hormones were noted. Intravenous high-dose hydrocortisone was initiated, followed by oral hydrocortisone in a progressively decreasing dose to address this episode of anti-PD-1 therapy-induced hypophysitis.&lt;/p&gt;&lt;p&gt;However, the patient passed away one week later due to refractory status epilepticus, which was likely multifactorial. Possible contributing factors include subdural hematomas (with acute mass effect noted at a later stage), pembrolizumab-induced neurotoxicity, and metabolic disturbances secondary to hypophysitis (such as severe hyponatremia and hypoglycemia).&lt;/p&gt;&lt;p&gt;ENKTCL is a rare non-Hodgkin's lymphoma that rarely spreads to the CNS. Stage III/IV disease significan","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1084-1085"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of HFE mutations on thrombotic risk in patients with idiopathic erythrocytosis: A single-centre study","authors":"Irene Bertozzi,&nbsp;Andrea Benetti,&nbsp;Elisabetta Cosi,&nbsp;Martina Zerbinati,&nbsp;Cecilia Fortino,&nbsp;Maria Luigia Randi,&nbsp;Paolo Simioni","doi":"10.1002/jha2.1019","DOIUrl":"https://doi.org/10.1002/jha2.1019","url":null,"abstract":"&lt;p&gt;Idiopathic erythrocytosis (IE) is characterized by an increase in red blood cell mass without an identified cause. Diagnosis of IE is based on exclusion of all the known forms of primary and secondary acquired erythrocytosis and various congenital primary and secondary polycythaemias [&lt;span&gt;1-3&lt;/span&gt;]. Recent studies have demonstrated a genetic complexity of IE, detecting the presence of several genetic variants in genes involved or suspected of being involved in erythrocytosis [&lt;span&gt;4, 5&lt;/span&gt;]. In particular, &lt;i&gt;HFE&lt;/i&gt; mutations are frequently observed in patients with IE, postulating that iron metabolism impairment is a possible underlying cause for erythrocytosis [&lt;span&gt;6, 7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;IE shows a peculiar clinical phenotype (male, young, isolated erythrocytosis), a trend for a stable disease with no tendency to spontaneous progression to myelofibrosis or acute leukaemia, but a relevant risk of thrombosis, especially arterial events, also in young patients [&lt;span&gt;5, 8, 9&lt;/span&gt;]. To date, no clear factors related to the increased thrombotic risk in IE have been established, therefore current therapeutic indications are aimed only at the management of cardiovascular risk factors. It has been shown that high haematocrit independently promotes arterial thrombosis by increasing the rate of platelet deposition and thrombus growth in spite of the absence of a clonal disease [&lt;span&gt;10&lt;/span&gt;], but the role of mutational status in thrombotic risk assessment has never been explored in patients with IE.&lt;/p&gt;&lt;p&gt;We studied 100 patients referred to our department, with a diagnosis of IE and an available complete medical history, including common cardiovascular risk factors (hypertension, diabetes, dyslipidaemia and active smoking). None of them carried &lt;i&gt;JAK2&lt;/i&gt; V617F or exon 12 mutations [&lt;span&gt;1&lt;/span&gt;]. Congenital primary and secondary polycythaemias were excluded in the absence of a familial pattern (i.e., at least one relative with erythrocytosis) and known mutations in &lt;i&gt;EPO-R&lt;/i&gt; or Oxygen Sensing Pathway genes [&lt;span&gt;2, 3&lt;/span&gt;]. A targeted next-generation sequencing (NGS) panel for patients with unexplained erythrocytosis was set up, including genes involved or suspected to be involved in erythrocytosis (Supporting information). Clinical and laboratory data of the patients are shown in Table 1.&lt;/p&gt;&lt;p&gt;All patients gave written informed consent. The protocol was approved by the local Institutional Ethical Committee (Azienda Ospedaliera di Padova, ref: 3922/AO/16). The study was conducted in compliance with the principles of the Declaration of Helsinki. The statistical tests adopted were logistic regression model for univariate and bivariate analysis and Cox regression model for survival analysis. Survival curve has been prepared with Kaplan–Meier method and compared with log rank test.&lt;/p&gt;&lt;p&gt;Sixty-seven (67%) patients carry at least one gene variant detected by the NGS study (Table S1). Forty-seven (47%) patients carry at least a mutat","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1086-1088"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genomic landscape of transformed splenic diffuse red pulp small B-cell lymphoma","authors":"Marta Grau,&nbsp;Melina Pol,&nbsp;Anna Montaner,&nbsp;Pablo Mozas,&nbsp;Ferran Nadeu,&nbsp;Ian Márquez-López,&nbsp;Jose Ramon Álamo,&nbsp;Alba Navarro,&nbsp;Daniel Martinez,&nbsp;Gerard Frigola,&nbsp;Olga Balagué,&nbsp;Mónica Lopez-Guerra,&nbsp;Dolors Colomer,&nbsp;Silvia Ruiz-Gaspà,&nbsp;Melika Bashiri,&nbsp;Juan Correa,&nbsp;Eva Giné,&nbsp;Armando López-Guillermo,&nbsp;Elias Campo,&nbsp;Cristina López,&nbsp;Estella Matutes,&nbsp;Sílvia Beà","doi":"10.1002/jha2.1018","DOIUrl":"https://doi.org/10.1002/jha2.1018","url":null,"abstract":"<p>The genetic landscape underlying the transformation of splenic diffuse red pulp small B-cell lymphoma (SDRPL) is not well understood. The present study aimed to unravel the genomic alterations involved in the progression and transformation of SDRPL. We performed genetic studies on both SDRPL and subsequent or synchronous diffuse large B cell lymphoma (DLBCL) samples in three SDRPL patients who eventually developed DLBCL. Our findings revealed that SDRPL cases progressing to DLBCL acquired genomic alterations in genes related to the cell cycle (<i>CDKN2A/B, TP53, MYC</i> and <i>CCND3</i>) and B cell development (<i>BCL6</i>).</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1014-1020"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-life data of luspatercept in lower-risk myelodysplastic syndromes advocate new research objectives","authors":"Bert Heyrman,&nbsp;Stef Meers,&nbsp;Sélim Sid,&nbsp;Natalie Put,&nbsp;Koen Theunissen,&nbsp;Koen Van Eygen,&nbsp;Nathan De Beule,&nbsp;Maxime Clauwaert,&nbsp;Helena Maes,&nbsp;Alexander Salembier,&nbsp;Jan Lemmens,&nbsp;Ann Van De Velde,&nbsp;Dominik Selleslag,&nbsp;Jason Bouziotis,&nbsp;Ann De Becker,&nbsp;Sébastien Anguille","doi":"10.1002/jha2.1027","DOIUrl":"https://doi.org/10.1002/jha2.1027","url":null,"abstract":"&lt;p&gt;Myelodysplastic syndromes (MDS) are characterized by ineffective haematopoiesis and a variable risk of progression to acute myeloid leukaemia (AML) [&lt;span&gt;1&lt;/span&gt;]. Treatment options are limited and eventually most patients become transfusion-dependent. Transfusion dependency is associated with a decreased quality of life and reduced survival. Transfusion independence (TI) has thus become a primary endpoint in nearly all clinical trials in lower-risk MDS (LR-MDS).&lt;/p&gt;&lt;p&gt;MDS with ring sideroblasts (MDS-RS), renamed MDS with low blasts and SF3B1 mutation in the World Health Organization (WHO) 2022 classification, has a more favourable prognosis compared to other subtypes [&lt;span&gt;2, 3&lt;/span&gt;]. First-line treatment for anaemia is erythropoiesis-stimulating agents (ESA). ESA has been shown to increase haemoglobin (Hb) by about 60% with an estimated median duration of response of 20 months [&lt;span&gt;4&lt;/span&gt;]. The increase in Hb correlates with a positive effect on quality of life [&lt;span&gt;5&lt;/span&gt;]. Patients with MDS-RS who are transfusion dependent and failed first-line ESA or who are unlikely to respond to ESA (baseline EPO level &gt;200 IU/L) can be treated with luspatercept, a first-in-class erythroid maturating agent. In a phase 3 study (MEDALIST trial) TI for a minimum of 8 weeks during the first 24 weeks was observed in 38% of the patients. At 24 weeks, 65.3% continued in the extension phase because of the clinical benefit of luspatercept at that time [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Real-life data of luspatercept so far are limited and response varies from 18% to &gt;90% [&lt;span&gt;7, 8&lt;/span&gt;]. The safety profile as reported in the MEDALIST trial was confirmed in real life with fatigue and cardiovascular events being the most frequent adverse events (AEs) [&lt;span&gt;9&lt;/span&gt;]. In terms of quality of life (QoL), a secondary endpoint in the MEDALIST trial, luspatercept could not demonstrate any benefit compared to placebo [&lt;span&gt;10&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We collected Belgian real-life data of patients who started luspatercept from the start of reimbursement (1 August 2021) with data cut-off on 28 November 2023. Data were collected during December 2023 and January 2024. The ethical committee of the University Hospital Antwerp approved a minimum risk protocol that allowed retrospective collection of the data in different centres and analysis of the data.&lt;/p&gt;&lt;p&gt;Hospital pharmacies of participating centres provided a list of luspatercept-exposed patients. Patients who received luspatercept in the context of a clinical trial or with a follow-up less than 3 months from the first dose administration were excluded. Transfusion burden (TB) was defined as no TB (0 packed cells/8 weeks), low TB (1–4 units of packed cells/8 weeks), intermediate TB (5–7 packed cells/8 weeks) and high TB (&gt; 7 units of packed cells/8 weeks). Erythroid response was defined as a change in the TB category or an increase in Hb level of at least 1.5 g/dL for patients with no TB. We analysed the duration ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1096-1099"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond myeloid neoplasms germline guidelines: Validation of the thresholds criteria in the search of germline predisposition variants","authors":"Julia Mestre,&nbsp;Lorea Chaparro,&nbsp;Ana Manzanares,&nbsp;Blanca Xicoy,&nbsp;Lurdes Zamora,&nbsp;Francesc Sole,&nbsp;Oriol Calvete","doi":"10.1002/jha2.1012","DOIUrl":"https://doi.org/10.1002/jha2.1012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Germline predisposition to myeloid neoplasms can be suspected in patients younger than 50 years or when harboring mutations with a variant allele frequency (VAF) higher than 30% for point mutations in specific genes. To investigate the VAF thresholds’ accuracy we have explored the prevalence of germline variants below the 30% VAF threshold.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 40 variants with VAF lower than 30% in bone marrow samples of myeloid neoplasm patients were selected and studied in CD3⁺ cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All the selected variants were not found in CD3⁺ cells except one variant in the <i>SF3B1</i> gene. However, the whole series was found somatic. Selected variants were also evaluated with our previously studied series of 52 variants with VAF higher than 30%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study suggests that variants with VAF below 30% are strong somatic candidates but the variants with VAF higher than 30% cannot be considered of germline origin.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1021-1027"},"PeriodicalIF":0.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid neoplasm post cytotoxic treatment in patients with multiple myeloma","authors":"Ke Xu,&nbsp;Eleanor Kaffo,&nbsp;Robert Baker,&nbsp;Elisabeth Nacheva,&nbsp;Annabel McMillan,&nbsp;Lydia Lee,&nbsp;Xenofon Papanikolaou,&nbsp;Rakesh Popat,&nbsp;Jonathan Sive,&nbsp;Kwee Yong,&nbsp;Neil Rabin,&nbsp;Charalampia Kyriakou,&nbsp;Rajeev Gupta","doi":"10.1002/jha2.1017","DOIUrl":"https://doi.org/10.1002/jha2.1017","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Myeloma and monoclonal gammopathy of undetermined significance patients are at higher risk of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) [&lt;span&gt;1&lt;/span&gt;]. Cytotoxic treatment, including alkylating agents such as high-dose melphalan (HDM), further increases their risk of post cytotoxic treatment-myeloid neoplasm (pCT-MN) [&lt;span&gt;2&lt;/span&gt;]. HDM followed by autologous stem cell transplantation (ASCT) prolongs progression-free survival. It is the standard of care in the UK for transplant-eligible patients. Our centre performs 150 HDM ASCT every year. The study aimed to review pCT-MN cases among patients with multiple myeloma in our centre and describe their characteristics, cytogenetics and molecular risk, treatment regimen and outcome.&lt;/p&gt;&lt;p&gt;We retrospectively reviewed all new pCT-MN cases (as defined by WHO 5th edition classification) with background myeloma, whose pCT-MN was diagnosed and treated at our centre's specialist integrated haematological malignancy diagnostic service. The data cutoff date was 30 June 2024. Our standard diagnostic MDS/AML fluorescence in situ hybridization (FISH) panel consists of break apart or fusion probes targeting &lt;i&gt;KMT2A&lt;/i&gt;, &lt;i&gt;CBFB::MYH11&lt;/i&gt; inv(16), &lt;i&gt;RUNX1T1::RUNX1&lt;/i&gt; t(8;21), &lt;i&gt;PML::RARA&lt;/i&gt; t(15:17) and &lt;i&gt;MECOM&lt;/i&gt;, and probes targeting 5q, 7q and 17p (Cytocell). Molecular karyotyping (8 × 60K oligonucleotide arrays, Agilent) was used to assess copy number variations across the whole genome. Targeted myeloid NGS panel analysis (Table S1) was used according to the manufacturer's instructions to detect pathogenic variants.&lt;/p&gt;&lt;p&gt;A total of 906 patients with multiple myeloma were actively followed up at our centre between 1 January 2018 and 31 December 2022. They were diagnosed with myeloma between 2004 and 2022. The median age of myeloma diagnosis was 60 years (range: 28–93 years). Six pCT-MN patients with multiple myeloma were identified. Their characteristics are summarised in Table 1. All six patients had previous alkylator therapy and presented with progressive cytopenia. Five were male and one was female. The median age of symptomatic myeloma diagnosis was 66 years (range: 58–77 years). Four were standard risk on CD138-cell FISH. Two had no FISH result. All five transplant-eligible patients had HDM ASCT. Other myeloma treatments they received were bortezomib thalidomide and dexamethasone (VTD), ixazomib lenalidomide and dexamethasone (IRD), lenalidomide and dexamethasone (RD), daratumumab, CC220, bortezomib lenalidomide and dexamethasone (VRD), cyclophosphamide lenalidomide and dexamethasone (CRD), isatuximab pomalidomide and dexamethasone (IsaPD), bortezomib cyclophosphamide and dexamethasone (VCD) and PD. The median lines of myeloma treatment received were two (range:1–6). The median time from diagnosis of myeloma to diagnosis of pCT-MN was 83 months (range: 18–233 months). Two patients were diagnosed with AML, two with MDS-excess of blast (EB) and two with MD","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1089-1091"},"PeriodicalIF":0.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of bleeding risk in patients who received pirtobrutinib in the presence or absence of antithrombotic therapy","authors":"Nicole Lamanna,&nbsp;Constantine S. Tam,&nbsp;Jennifer A. Woyach,&nbsp;Alvaro J. Alencar,&nbsp;M. Lia Palomba,&nbsp;Pier Luigi Zinzani,&nbsp;Ian W. Flinn,&nbsp;Bita Fakhri,&nbsp;Jonathon B. Cohen,&nbsp;Arrin Kontos,&nbsp;Heiko Konig,&nbsp;Amy S. Ruppert,&nbsp;Anindya Chatterjee,&nbsp;Richard Sizelove,&nbsp;Livia Compte,&nbsp;Donald E. Tsai,&nbsp;Wojciech Jurczak","doi":"10.1002/jha2.1013","DOIUrl":"https://doi.org/10.1002/jha2.1013","url":null,"abstract":"<p>Clinical bleeding events are reported here from 773 patients with B-cell malignancies receiving pirtobrutinib monotherapy from the phase 1/2 BRUIN study (ClinicalTrials.gov identifier: NCT03740529), either in the presence or absence of antithrombotic therapy (antithrombotic exposed [AT-E], <i>n</i> = 216; antithrombotic nonexposed [AT-NE], <i>n</i> = 557). Among the AT-E cohort, 51.9% received platelet aggregation inhibitors, 36.6% received direct factor Xa inhibitors, 18.5% received heparins, 5.6% received salicylic acid for indications other than platelet aggregation inhibition, and 2.3% received thrombolytics. Warfarin was not permitted. Any-grade bleeding/bruising events occurred in 97 patients (44.9%; 95% confidence interval [CI], 38.3–51.5) in the AT-E cohort and 181 patients (32.5%; 95% CI, 28.6–36.4) in the AT-NE cohort. Most bleeding/bruising events in both cohorts began within the first 6 months of treatment (AT-E: 65.4%; AT-NE: 72.5%). Contusion was the most common bleeding/bruising event in both cohorts (AT-E: 22.7%; AT-NE: 18.1%). Grade ≥3 bleeding/bruising events were reported in six patients (2.8%) in the AT-E cohort and 11 patients (2.0%) in the AT-NE cohort. Bleeding/bruising events requiring or prolonging hospitalization were reported in 2.3% and 1.6% of patients in the AT-E and AT-NE cohorts, respectively. No bleeding/bruising events led to pirtobrutinib dose reduction or permanent discontinuation in the AT-E cohort, and one patient (0.2%) in the AT-NE cohort experienced an event requiring dose reduction. These data support the safety of pirtobrutinib in patients requiring antithrombotic therapies.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"929-939"},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating plasmablasts in dengue fever","authors":"Robert Noble,&nbsp;Sarah Clifford,&nbsp;Alasdair Duguid","doi":"10.1002/jha2.1011","DOIUrl":"https://doi.org/10.1002/jha2.1011","url":null,"abstract":"<p>A 31-year-old man presented to the emergency department with a 5-day history of fever, headache and lower back pain which started within 48 h of travelling from his residence in Delhi, India to the United Kingdom. Admission full blood count showed a moderate thrombocytopenia (platelets 76 × 10⁹/L) with otherwise preserved counts (haemoglobin 139 g/L; white cell count 3.8 × 10⁹/L).</p><p>A blood film demonstrated frequent abnormal lymphoid cells, shown above, with deep basophilic cytoplasms, large eccentrically placed nuclei, nucleoli and perinuclear hoff. Immunophenotyping was consistent with a population of plasmablasts; CD19+ CD10− CD20− HLADR+ CD38 (bright) and CD138 (heterogeneous) without surface light chain expression [<span>1</span>].</p><p>The clinical presentation was felt to be in keeping with dengue virus infection which was subsequently confirmed by detecting dengue virus RNA by RT-PCR in conjunction with a positive IgG and indeterminate IgM ELISA. The patient's condition improved with supportive treatment over the following 72 h with resolution of the thrombocytopenia and circulating plasmablasts.</p><p>Dengue is a mosquito-borne viral illness which should be suspected in a febrile traveller from an endemic region displaying suitable clinical features within 2 weeks of last possible exposure [<span>2</span>]. There is a strong association between acute dengue infection and polyclonal plasmablast response. Atypical plasmacytoid cells with severe thrombocytopenia in the returning traveller with fever should alert treating teams to the possibility of dengue virus infection, thereby potentially avoiding further invasive testing for a primary bone marrow pathology (Figure 1, all four panels: circulating plasmablasts present on periphral blood film. M-G-G, x100 objective).</p><p>R. Noble wrote the manuscript. A. Duguid and S. Clifford revised the manuscript.</p><p>The authors declare no conflicts of interest.</p><p>The authors received no specific funding for this work.</p><p>The information presented in this manuscript is deidentified, and there is minimal risk to the patient's privacy or confidentiality.</p><p>No material from other sources is included in this manuscript.</p><p>The authors have confirmed that informed patient consent was obtained.</p><p>Clinical trial registration is not needed for this submission.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1080-1081"},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}