Irene Bertozzi, Andrea Benetti, Elisabetta Cosi, Martina Zerbinati, Cecilia Fortino, Maria Luigia Randi, Paolo Simioni
{"title":"Impact of HFE mutations on thrombotic risk in patients with idiopathic erythrocytosis: A single-centre study","authors":"Irene Bertozzi, Andrea Benetti, Elisabetta Cosi, Martina Zerbinati, Cecilia Fortino, Maria Luigia Randi, Paolo Simioni","doi":"10.1002/jha2.1019","DOIUrl":"https://doi.org/10.1002/jha2.1019","url":null,"abstract":"<p>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 [<span>1-3</span>]. 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 [<span>4, 5</span>]. In particular, <i>HFE</i> mutations are frequently observed in patients with IE, postulating that iron metabolism impairment is a possible underlying cause for erythrocytosis [<span>6, 7</span>].</p><p>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 [<span>5, 8, 9</span>]. 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 [<span>10</span>], but the role of mutational status in thrombotic risk assessment has never been explored in patients with IE.</p><p>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 <i>JAK2</i> V617F or exon 12 mutations [<span>1</span>]. 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 <i>EPO-R</i> or Oxygen Sensing Pathway genes [<span>2, 3</span>]. 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.</p><p>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.</p><p>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}
Marta Grau, Melina Pol, Anna Montaner, Pablo Mozas, Ferran Nadeu, Ian Márquez-López, Jose Ramon Álamo, Alba Navarro, Daniel Martinez, Gerard Frigola, Olga Balagué, Mónica Lopez-Guerra, Dolors Colomer, Silvia Ruiz-Gaspà, Melika Bashiri, Juan Correa, Eva Giné, Armando López-Guillermo, Elias Campo, Cristina López, Estella Matutes, Sílvia Beà
{"title":"The genomic landscape of transformed splenic diffuse red pulp small B-cell lymphoma","authors":"Marta Grau, Melina Pol, Anna Montaner, Pablo Mozas, Ferran Nadeu, Ian Márquez-López, Jose Ramon Álamo, Alba Navarro, Daniel Martinez, Gerard Frigola, Olga Balagué, Mónica Lopez-Guerra, Dolors Colomer, Silvia Ruiz-Gaspà, Melika Bashiri, Juan Correa, Eva Giné, Armando López-Guillermo, Elias Campo, Cristina López, Estella Matutes, 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}
Bert Heyrman, Stef Meers, Sélim Sid, Natalie Put, Koen Theunissen, Koen Van Eygen, Nathan De Beule, Maxime Clauwaert, Helena Maes, Alexander Salembier, Jan Lemmens, Ann Van De Velde, Dominik Selleslag, Jason Bouziotis, Ann De Becker, Sébastien Anguille
{"title":"Real-life data of luspatercept in lower-risk myelodysplastic syndromes advocate new research objectives","authors":"Bert Heyrman, Stef Meers, Sélim Sid, Natalie Put, Koen Theunissen, Koen Van Eygen, Nathan De Beule, Maxime Clauwaert, Helena Maes, Alexander Salembier, Jan Lemmens, Ann Van De Velde, Dominik Selleslag, Jason Bouziotis, Ann De Becker, Sébastien Anguille","doi":"10.1002/jha2.1027","DOIUrl":"https://doi.org/10.1002/jha2.1027","url":null,"abstract":"<p>Myelodysplastic syndromes (MDS) are characterized by ineffective haematopoiesis and a variable risk of progression to acute myeloid leukaemia (AML) [<span>1</span>]. 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).</p><p>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 [<span>2, 3</span>]. 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 [<span>4</span>]. The increase in Hb correlates with a positive effect on quality of life [<span>5</span>]. Patients with MDS-RS who are transfusion dependent and failed first-line ESA or who are unlikely to respond to ESA (baseline EPO level >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 [<span>6</span>].</p><p>Real-life data of luspatercept so far are limited and response varies from 18% to >90% [<span>7, 8</span>]. 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) [<span>9</span>]. In terms of quality of life (QoL), a secondary endpoint in the MEDALIST trial, luspatercept could not demonstrate any benefit compared to placebo [<span>10</span>].</p><p>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.</p><p>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 (> 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}
Julia Mestre, Lorea Chaparro, Ana Manzanares, Blanca Xicoy, Lurdes Zamora, Francesc Sole, Oriol Calvete
{"title":"Beyond myeloid neoplasms germline guidelines: Validation of the thresholds criteria in the search of germline predisposition variants","authors":"Julia Mestre, Lorea Chaparro, Ana Manzanares, Blanca Xicoy, Lurdes Zamora, Francesc Sole, 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<sup>+</sup> cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All the selected variants were not found in CD3<sup>+</sup> 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}
Ke Xu, Eleanor Kaffo, Robert Baker, Elisabeth Nacheva, Annabel McMillan, Lydia Lee, Xenofon Papanikolaou, Rakesh Popat, Jonathan Sive, Kwee Yong, Neil Rabin, Charalampia Kyriakou, Rajeev Gupta
{"title":"Myeloid neoplasm post cytotoxic treatment in patients with multiple myeloma","authors":"Ke Xu, Eleanor Kaffo, Robert Baker, Elisabeth Nacheva, Annabel McMillan, Lydia Lee, Xenofon Papanikolaou, Rakesh Popat, Jonathan Sive, Kwee Yong, Neil Rabin, Charalampia Kyriakou, Rajeev Gupta","doi":"10.1002/jha2.1017","DOIUrl":"https://doi.org/10.1002/jha2.1017","url":null,"abstract":"<p>Dear Editor,</p><p>Myeloma and monoclonal gammopathy of undetermined significance patients are at higher risk of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) [<span>1</span>]. Cytotoxic treatment, including alkylating agents such as high-dose melphalan (HDM), further increases their risk of post cytotoxic treatment-myeloid neoplasm (pCT-MN) [<span>2</span>]. 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.</p><p>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 <i>KMT2A</i>, <i>CBFB::MYH11</i> inv(16), <i>RUNX1T1::RUNX1</i> t(8;21), <i>PML::RARA</i> t(15:17) and <i>MECOM</i>, 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.</p><p>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}
Nicole Lamanna, Constantine S. Tam, Jennifer A. Woyach, Alvaro J. Alencar, M. Lia Palomba, Pier Luigi Zinzani, Ian W. Flinn, Bita Fakhri, Jonathon B. Cohen, Arrin Kontos, Heiko Konig, Amy S. Ruppert, Anindya Chatterjee, Richard Sizelove, Livia Compte, Donald E. Tsai, Wojciech Jurczak
{"title":"Evaluation of bleeding risk in patients who received pirtobrutinib in the presence or absence of antithrombotic therapy","authors":"Nicole Lamanna, Constantine S. Tam, Jennifer A. Woyach, Alvaro J. Alencar, M. Lia Palomba, Pier Luigi Zinzani, Ian W. Flinn, Bita Fakhri, Jonathon B. Cohen, Arrin Kontos, Heiko Konig, Amy S. Ruppert, Anindya Chatterjee, Richard Sizelove, Livia Compte, Donald E. Tsai, 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, Sarah Clifford, 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 × 10<sup>9</sup>/L) with otherwise preserved counts (haemoglobin 139 g/L; white cell count 3.8 × 10<sup>9</sup>/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}
Tulasi Geevar, Yasmeen Abulkhair, Cuihong Wei, Hong Chang
{"title":"Concurrent hyperdiploid acute myeloid leukemia and trisomy 12+ chronic lymphocytic leukemia","authors":"Tulasi Geevar, Yasmeen Abulkhair, Cuihong Wei, Hong Chang","doi":"10.1002/jha2.1009","DOIUrl":"https://doi.org/10.1002/jha2.1009","url":null,"abstract":"<p>A 75-year-old man presented with weakness and night sweats of 2 weeks duration. He had anemia (75 g/L), and thrombocytopenia (22 × 10<sup>9</sup>/L) with a white blood cell count of 10.6 × 10<sup>9</sup>/L. Peripheral smear (Figure 1, panel A, 10x objective) showed lymphocytosis (7.6 × 10<sup>9</sup>/L) and 8% promonocytes/blasts. Bone marrow aspirate showed 60% blasts/promonocytes and lymphocytosis (panel B, 63x objective). Biopsy (panel C, 20x objective) showed small lymphoid aggregates, positive for CD5/CD20 (panels D&E, 10x objective), and sheets of MPO+/CD117+ blasts (panels F and G, 20x objectives). Flow cytometry (panels I–M) demonstrated ∼40% atypical monocytic cells (green) and ∼25% blasts (red) which were positive for MPO/HLA-DR/CD64/CD117 and negative for CD34/CD14. There were ∼45% lambda restricted B-cells (pink), positive for CD5/CD19/CD20 (dim)/CD23/CD43/CD200. Karyotyping showed 50, XY with trisomy for chromosomes 2, 8, 19, 21, and without structural abnormalities. Next Generation Sequencing showed NRAS mutation with a variant allele frequency of 17%. Fluorescent in situ hybridization (FISH) in addition showed trisomy 12. A diagnosis of concomitant hyperdiploid acute myeloid leukemia (H-AML) and B-chronic lymphocytic leukemia (B-CLL) with trisomy 12 was rendered.</p><p>A custom interphase FISH was performed using probes for chromosomes 8 and 12 (panel H) which showed trisomy 8 (green signals) in larger nuclei and trisomy 12 (red signals) in smaller nuclei. Both abnormalities were not detected within the same nuclei, indicating the different clonal origin of blasts and CLL cells.</p><p>The patient was treated with an induction regimen consisting of 7 days of cytarabin and 3 days of daunorubicin. He entered a hematologic remission for AML, also with a marked reduction in CLL clones in the bone marrow. He completed two cycles of consolidation therapy but relapsed 14 months after treatment, with 25% blasts in the bone marrow. He was started on venetoclax and azacytidine. His disease progressed, and he succumbed to his illness 2 years after the initial diagnosis.</p><p>Hyperdiploidy (≥3 trisomies without structural abnormalities) is a rare event in AML, reported in < 2% of cases, and confers an intermediate prognosis [<span>1</span>]. It is important to distinguish H-AML from AML with complex karyotype (≥3 unrelated chromosome abnormalities in the absence of other recurring genetic abnormalities and excluding hyperdiploidy) as the latter entity has a poor prognosis as per the 2022 ELN recommendations [<span>2, 3</span>]. Trisomy 12 occurs in ∼20% of CLL, associated with intermediate prognosis [<span>4</span>]. The rare concurrence of H-AML and trisomy 12 B-CLL in this case may represent two separate disease processes.</p><p>Tulasi Geevar, Yasmeen Abulkhair, and Cuihong Wei collected data; Tulasi Geevar and Hong Chang wrote the paper; Hong Chang supervised the study.</p><p>The authors declare no conflict of interest.</p><p>The ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1082-1083"},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438980","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}
Orla McCourt, Paul Maciocia, Claire Roddie, Angela Hwang, Leigh Wood, Aikaterini Panopoulou, Deborah Ann Springell, Maise Al Bakir, Maeve O'Reilly
{"title":"Single-centre experience of implementing physiotherapist-led prehabilitation for chimeric antigen receptor T cell therapy","authors":"Orla McCourt, Paul Maciocia, Claire Roddie, Angela Hwang, Leigh Wood, Aikaterini Panopoulou, Deborah Ann Springell, Maise Al Bakir, Maeve O'Reilly","doi":"10.1002/jha2.1006","DOIUrl":"https://doi.org/10.1002/jha2.1006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>This report outlines the evaluation of physiotherapist-led prehabilitation/rehabilitation for recipients of chimeric antigen receptor T (CAR-T) cell therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A hybrid approach was used, incorporating in-person assessment of quality of life and functional capacity (6-min walk test and timed sit-to-stand test), and a personalised home exercise programme with remotely delivered physiotherapist support pre/post-admission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Functional deficits were prevalent at referral for CAR-T. Prehabilitation and rehabilitation were highly acceptable to patients, and improvements in functional capacity were documented pre-admission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This data highlights the importance of pre-CAR-T functional assessment and prehabilitation to optimise preparation and recovery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1033-1037"},"PeriodicalIF":0.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439017","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}
Anoop K. Enjeti, Natasha Walker, Oliver Fahey, Elizabeth Johnston, Hannah Legge-Wilkinson, Nateika Ramsurrun, Jonathan Sillar, Lisa F. Lincz, Andrew Ziolkowski, David Mossman
{"title":"Certainty in uncertainty: Determining the rate and reasons for reclassification of variants of uncertain significance in haematological malignancies","authors":"Anoop K. Enjeti, Natasha Walker, Oliver Fahey, Elizabeth Johnston, Hannah Legge-Wilkinson, Nateika Ramsurrun, Jonathan Sillar, Lisa F. Lincz, Andrew Ziolkowski, David Mossman","doi":"10.1002/jha2.1002","DOIUrl":"https://doi.org/10.1002/jha2.1002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Variants of uncertain significance (VUS) are commonly reported in cancer with the widespread adoption of diagnostic massive parallel sequencing. The rate of reclassification of VUS in patients with haematological malignancy is not known and we evaluated this retrospectively. We also investigated whether re-evaluating VUS in 12–24 months or greater than 24 months post-initial classification was significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A retrospective audit of patients with haematological malignancies referred to the Molecular Medicine Department at the John Hunter Hospital in Newcastle, Australia between September 2018 and December 2021. Data was analysed for VUS, which was then re-analysed in standard software using current somatic variant guidelines. Proportions of VUS at baseline were compared to post-re-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The most common diagnoses in the patient cohort (<i>n</i> = 944) were acute myelogenous leukaemia (41%), myelodysplastic syndrome (31%), and chronic myelomonocytic leukaemia (7%). A total of 210 VUS were re-analysed. The most common VUS were in the TET2 (20%), RUNX1 (10%) and DNMT3A (9%) genes. A total of 103 were re-analysed at 24–39 months post-initial classification and 107 variants were re-analysed between 12 and 24 months post-initial classification. Of these, 33 (16%) of VUS were re-classified at 24–39 months and 12 (11%) were re-classified at 12–24 months post-initial classification. The most common variants that were re-classified in both groups were CSF3R (32%), TET2 (29%), ASXL1 (11%) and ZRSR2 (11%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study on reclassification of VUS in blood cancers demonstrated that one in seven VUS were re-classified 12 months post initial classification. This can inform practice guidelines and potentially impact the prognosis, diagnosis and treatment of haematological malignancies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"957-963"},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438900","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}