EMJ Hematology最新文献

{"title":"Transplantation Versus Gene Therapy for Sickle Cell Disease","authors":"Jivitesh Newoor","doi":"10.33590/emjhematol/10301924.","DOIUrl":"https://doi.org/10.33590/emjhematol/10301924.","url":null,"abstract":"","PeriodicalId":326555,"journal":{"name":"EMJ Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121065203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untangling Systemic Mastocytosis: An Update on Challenges in the Diagnosis and Treatment of Myeloid Neoplasms with Systemic Mastocytosis","authors":"Nicola Humphry","doi":"10.33590/emjhematol/10304572.","DOIUrl":"https://doi.org/10.33590/emjhematol/10304572.","url":null,"abstract":"This symposium was held on the first day of the 2023 European Hematology Association (EHA) Congress, held in Frankfurt, Germany. The main objective of the symposium was to gather experts from the field to raise awareness of the challenges in diagnosing and treating systemic mastocytosis (SM) with an associated haematologic neoplasm (AHN). Presentations focused on optimising the diagnosis of the SM component and recognising the different types of myeloid AHN. The expert panel considered the clinical management of SM-AHN, and how and when to prioritise the various disease components. The overarching message from the symposium was that diagnosis of SM-AHN is challenging, and SM is often missed in patients with a myeloid neoplasm, such as chronic myelomonocytic leukaemia (CMML), myelodysplastic/myeloproliferative neoplasm (MDS/MPN), myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN), as well as AHN being missed in patients with SM. Identification of a SM-AHN through serum tryptase and/or molecular testing for KITD816V mutation in peripheral blood in a patient with a previous diagnosis of a myeloid neoplasm allows potentially efficacious targeted treatment with KIT inhibitors, such as midostaurin and avapritinib. Although SM-AHN is associated with a poor prognosis, a correct diagnosis and detailed understanding of an individual’s disease can help to guide optimal treatment decisions, including when to prioritise SM treatment over AHN treatment, and vice versa.","PeriodicalId":326555,"journal":{"name":"EMJ Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131140087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steroid Toxicity in Immune Thrombocytopenia – A Series of Unfortunate Events: A Case Report","authors":"D. Chattopadhyay, A. Puthalath, U. Nath","doi":"10.33590/emjhematol/10307003.","DOIUrl":"https://doi.org/10.33590/emjhematol/10307003.","url":null,"abstract":"Immune thrombocytopenia (ITP) is a common bleeding disorder characterised by isolated thrombocytopenia, due to immune-mediated accelerated platelet destruction, usually without any specific or identifiable precipitating factor. ITP most commonly presents with bleeding associated with a low platelet count <100×109/L. Corticosteroids are the first line of treatment in adults. However, steroid-induced complications are widespread in patients with ITP, and sometimes are more atrocious than the risk of bleeding associated with thrombocytopenia. The authors report the case of a 29-year-old male with ITP with recurrent episodes of epistaxis, who was treated with prednisolone for 8 weeks and developed acne, steroid-induced hyperglycaemia, and urinary tract infection with epididymitis and pyocele. A few weeks later, the patient developed blurring of vision, and was found to have central serous chorioretinopathy. They were treated adequately for each of these complications, and had complete resolution of symptoms following cessation of steroids. While acne and hyperglycaemia are common, urinary tract infections with epididymitis and central serous chorioretinopathy are infrequent complications following steroid administration. The complexity of adverse events and the challenges in diagnosing and treating these unique complications prompted the authors to report this case.","PeriodicalId":326555,"journal":{"name":"EMJ Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126248478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infographic: Sickle Cell Disease","authors":"","doi":"10.33590/emjhematol/10306607","DOIUrl":"https://doi.org/10.33590/emjhematol/10306607","url":null,"abstract":"","PeriodicalId":326555,"journal":{"name":"EMJ Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129596722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBA1 Non-M41 Variants Are More Aggressive than UBA1 M41 Variants in Their Haematological Manifestations","authors":"M. Sakuma, C. Baer, M. Meggendorfer, C. Haferlach, W. Kern, T. Haferlach, W. Walter","doi":"10.33590/emjhematol/10308258.","DOIUrl":"https://doi.org/10.33590/emjhematol/10308258.","url":null,"abstract":"BACKGROUND AND AIMS\u0000In 2020, three somatic mutations in the X-linked gene UBA1, coding for an essential ubiquitin activating enzyme, were reported to cause VEXAS syndrome, a novel haemato-inflammatory disease that manifests with both cytopenias and autoinflammation.1 The mutations alter the start codon (M41) of the cytoplasmic isoform of UBA1, resulting in the cytoplasmic-only loss of function of UBA1. Approximately 50% of patients with VEXAS develop myelodysplastic syndrome (MDS), but interestingly progression to acute myeloid leukaemia (AML) is extremely rare. The speculated protective mechanisms of UBA1 mutations from malignant transformation intrigued the authors to retrospectively analyse the whole genome data from more than 4,000 patients diagnosed with various haematological malignancies (HM), which revealed 16 putative somatic non-M41 UBA1 variants.2 Most of the novel mutations surrounded either adenosine triphosphate-contacting, ubiquitin-contacting, or interdomain-interacting residues, which are considered to affect both the nuclear and cytoplasmic isoforms of UBA1. Surprisingly, secondary AML progression was not rare in patients harbouring the novel non-M41 UBA1 variants. Literature indicates involvement of UBA1 in DNA damage repair,3 which suggested mutations impairing UBA1 nuclear isoform may be more malignant than M41 variants.\u0000\u0000MATERIALS AND METHODS\u0000To further understand this difference, Munich Leukemia Laboratory (MLL), Germany, introduced the entire coding sequence of UBA1 in the gene panel for 9,771 samples sent for diagnostic testing. The somatic state of the variants were assigned based on the variant allele frequency as previously described,2 and the variants were further classified into priority variants, if they had been previously detected in symptomatic patients2,4,5 and surrounded the functional residues.6 All other variants were classified as variants of uncertain significance (VUS).\u0000\u0000RESULTS\u0000In this new screen, the authors detected 28 UBA1 variants in 42 patients (Figure 1). M41 variants were detected in 21 patients, non-M41 priority variants in seven patients, and non-M41 VUS in 15 patients (nine males; six females), including five patients with multiple mutations. All priority variants were detected in male patients.\u0000\u0000\u0000Figure 1: Detected UBA1 variants and associated diagnoses.\u0000Loci of variants are shown as circles on the genes, with their diagnoses colour coded. Loci of previously reported variants are shown in grey to denote recurrence. Known functional regions are highlighted by yellow within the gene. Females are denoted by squares.\u0000AAD: active adenylation domains; AML: acute myeloid leukaemia; CMML: chronic myelomonocytic leukaemia; FCCD: first catalytic cysteine half-domain; IAD: inactive adenylation domains; LPL: lymphoplasmacytic lymphoma; MDS: myelodysplastic syndrome; MM: multiple myeloma; MN-pCT: myeloid neoplasm post cytotoxic therapy; MPN: myeloproliferative neoplasm; SCCD: second catalytic cysteine half-","PeriodicalId":326555,"journal":{"name":"EMJ Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115197351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAS-ERK Pathway Genes Mutations in the Lesions from Various Tumour Loci in Multiple Myeloma","authors":"M. Soloveva, M. Solovev, I. Yakutik, B. Biderman, E. Nikulina, N. Risinskaya, T. Obukhova, A. Sudarikov, L. Mendeleeva","doi":"10.33590/emjhematol/10305683.","DOIUrl":"https://doi.org/10.33590/emjhematol/10305683.","url":null,"abstract":"BACKGROUND AND AIMS\u0000Despite the fact that activating mutations in RAS-ERK cascade genes are quite often detected in multiple myeloma (MM), the literature data on their prognostic value are contradictory.1,2 The tumour substrate should not only be analysed in the bone marrow and plasmacytoma, but also in the plasma circulating tumour DNA (ctDNA) for the heterogeneity of MM to be effectively analysed.3,4 The aim was to study the mutational status of KRAS, NRAS, and BRAF genes in the tumour substrate from different loci in MM.\u0000\u0000MATERIALS AND METHODS\u0000The single-centre study from October 2021–January 2023 included 70 patients with symptomatic MM (29 male, 41 female) aged 35–84 years (median: 58 years). Plasmocytomas were detected in 66% of the patients with MM according to CT data. They were detected in the bone of 40 patients and extramedullary in six. A fluorescence in situ hybridization (FISH) study of CD138+ cells was performed using DNA probes to detect translocations of 14q32/IgH, 8q24/MYC; deletions of 17p13/TP53, 13q14, 1p32; amplification of 1q21; and multiple trisomies (MetaSystems, Altlussheim, Germany). Upon detection of t(4;14) translocation, t(14;16) translocation, del17p13, and amplification of 1q21, the patient was assigned to a high cytogenetic risk group. DNA was isolated from samples of various localisation: CD138+ bone marrow cells (n=60), ctDNA (n=19), bone plasmacytoma (n=9), and extramedullary plasmacytoma (n=6). The mutational status of KRAS, NRAS, and BRAF genes was studied in the tumour substrate from different loci. KRAS and NRAS gene mutations were identified by Sanger sequencing on the Nanophor 05 genetic analyser (Institute for Analytical Instrumentation Russian Academy of Science, Saint Petersburg, Russia), and by next-generation sequencing on the MiSeq System genetic analyser (Illumina, San Diego, California, USA). The BRAF V600E mutation was determined by real-time allele-specific PCR with the device CFX96 Touch (Bio-Rad Laboratories Inc., Hercules, California, USA).\u0000\u0000RESULTS\u0000KRAS gene mutations were detected in 16% of patients (11/70), of which less than one-third (27%) had high-risk cytogenetic abnormalities. NRAS gene mutations were detected in another 16% of patients, while more than half (55%) were assigned to a high cytogenetic risk group. BRAF gene mutations were found in 9% of patients (6/70), one-third of whom had high-risk aberrations (Figure 1). Paired tumour samples (plasma ctDNA and CD138+ bone marrow cells) were analysed in 15 patients with MM. In 11 patients, mutations in any of the three genes were found in the bone marrow, while in five patients (45%) similar mutations were also detected in a paired sample of tumour ctDNA isolated from plasma. No cases with KRAS, NRAS, or BRAF gene mutation detected in the plasma and the absence of the corresponding mutation in the bone marrow were found. The mutational status of the three genes was analysed in 15 plasmacytoma samples (nine bone, six extramedullary). I","PeriodicalId":326555,"journal":{"name":"EMJ Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116460637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EHA 2023 Abstract Highlights","authors":"Emj","doi":"10.33590/emjhematol/10305989.","DOIUrl":"https://doi.org/10.33590/emjhematol/10305989.","url":null,"abstract":"The following selected highlights explore several fascinating abstracts that were presented at the 60th European Renal Association (ERA) Congress 2023. Topics covered include vascular access in haemodialysis, renal transplantation, acute kidney injury, IgA nephropathy, and cardiovascular risk in chronic kidney disease.","PeriodicalId":326555,"journal":{"name":"EMJ Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131036514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introducing the Concept of Patient Blood Management and Haemovigilance in Government Sector Hospitals of Sindh, Pakistan","authors":"S. Waheed, Brig Sarwar Khan, Shumaila Qamar, Erum Rafiq","doi":"10.33590/emjhematol/10308832.","DOIUrl":"https://doi.org/10.33590/emjhematol/10308832.","url":null,"abstract":"BACKGROUND AND AIMS\u0000Patient blood management encompasses all aspects of the transfusion decision-making process, beginning with the initial patient evaluation and continuing through clinical management.1 It involves the timely, multidisciplinary application of evidence-based medical and surgical concepts, aimed at diagnosing and appropriately treating anaemia, along with minimising surgical and iatrogenic blood losses and managing coagulopathic bleeding, as well as supporting the patient while appropriate treatment is initiated.1\u0000\u0000Haemovigilance is the set of surveillance procedures covering the entire blood transfusion chain, from the donation and processing of blood and its components, through to their provision and transfusion to patients, including their follow-up.2\u0000\u0000The restrictive transfusion threshold uses a lower haemoglobin concentration as a threshold for transfusion (most commonly 7–8 g/dL), and the liberal transfusion threshold uses a higher haemoglobin concentration as a threshold for transfusion (most commonly 9–10 g/dL).3\u0000\u0000MATERIALS AND METHODS\u0000In this retrospective analysis, the authors aimed to critique and study their own performance since the establishment of the Regional Blood Centre (RBC) Karachi (2020–2022), Pakistan, and its associated hospital-based blood banks (currently three).\u0000\u0000The authors calculated parameters, including cross match to transfusion ratio and transfusion index; introduced the concept of maximum surgical blood ordering schedule; assessed the cold chain maintenance through data loggers and transportation containers; reported transfusion reactions; and overviewed the overall haemovigiliance concept over 3 years’ time.\u0000\u0000RESULTS\u0000When the authors started their blood banking in government sector hospitals of Karachi, whole blood was being issued to the patients. From the first day, RBC Karachi worked on blood products and did not issue a single whole blood to any patient. Initially, the cross match to transfusion ratio was 15:1, but with time and management, at the end of third year, they achieved the ratio of 1.5–1.7:1 for different hospitals (Figure 1). Transfusion index was also calculated to be 0.2 at the start of 2020 and was reported to be 0.8 at the end of 2022.\u0000\u0000\u0000Figure 1: Graphical representation of cross match to transfusion ratio of red blood cells and its associated blood banks.\u0000\u0000CONCLUSION\u0000Initially, for 1.5 years, the authors were not able to get a single transfusion reaction reported; however, after several awareness and training sessions, and continuing medical education, they started getting transfusion reactions reporting around 2–3 times fortnightly. Initially, wastage was higher than utilisation; however, with hard work and communication, the authors were able to reduce the wastage and suggested the idea of a restrictive transfusion strategy, so that the right blood component is given to the right patient at the right time. It was a tough journey as there are, unfortunately, no haematologic ","PeriodicalId":326555,"journal":{"name":"EMJ Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126003911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interview: Janis Abkowitz","authors":"J. Abkowitz","doi":"10.33590/emjhematol/10306801","DOIUrl":"https://doi.org/10.33590/emjhematol/10306801","url":null,"abstract":"","PeriodicalId":326555,"journal":{"name":"EMJ Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130600598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interview: Cynthia Dunbar","authors":"","doi":"10.33590/emjhematol/10302040","DOIUrl":"https://doi.org/10.33590/emjhematol/10302040","url":null,"abstract":"","PeriodicalId":326555,"journal":{"name":"EMJ Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125728552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}