EJHaem最新文献

{"title":"Pneumonia in patients with chronic lymphocytic leukemia treated with venetoclax-based regimens: A real-world analysis of Polish Adult Leukemia Group (PALG)","authors":"Elżbieta Kalicińska,&nbsp;Paula Jablonowska-Babij,&nbsp;Marta Morawska,&nbsp;Elżbieta Iskierka-Jażdżewska,&nbsp;Joanna Drozd-Sokolowska,&nbsp;Ewa Paszkiewicz-Kozik,&nbsp;Łukasz Szukalski,&nbsp;Judyta Strzała,&nbsp;Urszula Gosik,&nbsp;Jakub Dębski,&nbsp;Iga Andrasiak,&nbsp;Anna Skotny,&nbsp;Krzysztof Jamroziak,&nbsp;Tomasz Wrobel","doi":"10.1002/jha2.1042","DOIUrl":"10.1002/jha2.1042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with chronic lymphocytic leukemia (CLL) are susceptible to infections that can affect their clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To assess: (1) the incidence of pneumonia in CLL patients treated with venetoclax-based regimens in a real-world setting, (2) the risk factors for event-free survival (EFS), and (3) overall survival (OS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicenter study included 322 patients from eight centers. Univariable and multivariable analyses (MVA) were performed, having the development of pneumonia during venetoclax-based treatment and OS as outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The most common complication was neutropenia (59%). During treatment with venetoclax-based regimens, 66 (20%) of patients developed pneumonia: 50 (23%) patients in the rituximab plus venetoclax (R-VEN) group, 13 (16%) patients in the obinutuzumab plus venetoclax (O-VEN) group (<i>p</i> = 0.15). Chronic obstructive pulmonary disease (COPD)/asthma, splenomegaly, elevated creatinine, and anemia &lt;8 g/dL were the risk factors for EFS in MVA (hazard ratio [HR] = 2.08, 95% confidence interval [CI], 1.16–3.74, <i>p</i> = 0.014; HR 1.73, 95% CI, 1.08–2.78, <i>p</i> = 0.02; HR 2.13, 95% CI, 1.10–4.11, <i>p</i> = 0.03, HR 3.58, 95% CI, 2.18–5.89, <i>p</i> &lt; 0.001, respectively). Relapsed/refractory (R/R) CLL patients treated with R-VEN with pneumonia had worse OS than those without (<i>p</i> &lt; 0.001). In patients treated with O-VEN, median OS did not differ between patients with and without pneumonia (<i>p</i> = 0.45).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our real-world study showed that pneumonia during venetoclax treatment occurs more frequently than reported in registration trials and has a negative impact on OS, especially in patients with R/R CLL treated with R-VEN. Neutropenia is not a risk factor for pneumonia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048990","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":"RUNX1::CBFA2T2 rearranged acute myeloid leukemia transformed from JAK2 V617F mutated primary myelofibrosis","authors":"Lina Han,&nbsp;Prasad Koduru,&nbsp;Miguel Cantu,&nbsp;Franklin Fuda,&nbsp;Weina Chen","doi":"10.1002/jha2.985","DOIUrl":"10.1002/jha2.985","url":null,"abstract":"<p>Acute myeloid leukemia (AML) with <i>RUNX1::CBFA2T2</i> fusion is rare with largely unknown clinicopathological features and genomic characterization. We present one such case of AML transformed from <i>JAK2</i> V617F mutated primary myelofibrosis and review the literature on this topic. The immunophenotype and the landscape of cooperative gene alterations in AML with <i>RUNX1::CBFA2T2</i> resemble those of AML with <i>RUNX1::RUNX1T1</i>, including expression of CD19, cooperative gene alterations in signaling pathway (<i>JAK2</i>), epigenetic/chromatin and cell cycle regulation (<i>TET2</i>, <i>SMC3</i>, and <i>CDKN2A/B</i>), and additional chromosomal abnormalities (trisomies 8 and 15). This case study provides insights into the pathogenesis of this rare subtype of AML.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1330-1334"},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848493","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 evolving treatment landscape of multiple myeloma in Portugal: A nation-wide retrospective cohort study of real-world clinical practice","authors":"Rui Bergantim,&nbsp;Catarina Geraldes,&nbsp;Cristina João,&nbsp;Paulo Lúcio,&nbsp;Manuel Neves,&nbsp;Fernanda Trigo,&nbsp;Hugo Pedrosa,&nbsp;Miguel Ventura,&nbsp;Susana Santos,&nbsp;Diogo Ramos","doi":"10.1002/jha2.1035","DOIUrl":"10.1002/jha2.1035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To characterize variations in real-world treatment patterns in multiple myeloma (MM) in Portugal over a 5-year period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective cohort multicenter study using secondary data of national hospital drug consumption database from 11 Portuguese public hospitals between 2017 and 2022.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Number of MM-treated patients increased 53% over 5 years (from 825 to 1266 patients). Constant slight predominance of male patients (55%), 82% over 60 years old (median age, 70 years), and half of newly diagnosed patients were transplant-eligible. The highest growth rate was in second-line treatments, with a sixfold increase in patients in fourth-line or beyond. First-line treatment pattern remained stable both in transplant-eligible (bortezomib, cyclophosphamide and dexamethasone (VCd_, bortezomib, thalidomide and dexamethasone (VTd), and bortezomib, lenalidomide and dexamethasone (VRd)) and noneligible patients (bortezomib, melphalan and prednisolone (VMP), VCd, and lenalidomide, dexamethasone (Rd)). Maintenance therapy increased from 5% to 16%, shifting from thalidomide to lenalidomide. Second and third lines were dominated by daratumumab-based regimens after 5 years. No standard of care in fourth-line treatment. Treatment duration increased in transplant-eligible due to maintenance therapy and in noneligible due to fourth-line treatments. Patients moved from first- to second-line more rapidly over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There was an increase in MM patients reaching advanced treatment lines and significant changes in the treatment patterns, driven by access to more effective frontline treatments and longer duration of treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1144-1153"},"PeriodicalIF":0.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848246","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":"Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report","authors":"Jasmine Naru,&nbsp;Megan Othus,&nbsp;ChenWei Lin,&nbsp;Melinda A. Biernacki,&nbsp;Marie Bleakley,&nbsp;Thomas R. Chauncey,&nbsp;Harry P. Erba,&nbsp;Min Fang,&nbsp;Matthew P. Fitzgibbon,&nbsp;Phillip R. Gafken,&nbsp;Richard G. Ivey,&nbsp;Jacob J. Kennedy,&nbsp;Travis D. Lorentzen,&nbsp;Soheil Meshinchi,&nbsp;Anna Moseley,&nbsp;Era L. Pogosova-Agadjanyan,&nbsp;Vivian M. Liu,&nbsp;Jerald P. Radich,&nbsp;Uliana J. Voytovich,&nbsp;Pei Wang,&nbsp;Jeffrey R. Whiteaker,&nbsp;Cheryl L. Willman,&nbsp;Feinan Wu,&nbsp;Amanda G. Paulovich,&nbsp;Derek L. Stirewalt","doi":"10.1002/jha2.1041","DOIUrl":"10.1002/jha2.1041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Acute myeloid leukemia (AML) remains one of the deadliest hematopoietic malignancies. A better understanding of the molecular biology governing AML may lead to improved risk stratification and facilitate the development of novel therapies. Proteins are responsible for much of the biology of cells. Several studies have examined the global proteome in bulk mononuclear cells (MNCs) from AML specimens, which are comprised a heterogenous population of cells at various stages of differentiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Given the potential impact of the nonleukemic cells on protein expression profiles, we applied an integrative proteogenomic approach utilizing next-generation sequencing and mass spectrometry-based proteomics to identify novel protein biomarkers in unsorted MNCs and viable leukemic blasts (VLBs) isolated from blood and bone marrow specimens obtained at the time of AML diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified significant differences in protein expression between VLBs and MNCs. Subsequent studies (<i>N</i> = 27) focused on proteomic profiling of VLBs that identified novel candidate biomarkers associated with mutational genotypes and clinical outcome, some of which were recapitulated in an independent cohort of patients. Using mass spectrometry, we also detected mutated protein products, some of which were predicted via in silico analyses to be potential neoantigens amenable to adoptive immunotherapy. As previously described, analyses comparing transcript and protein expression showed an overall modest correlation between mRNA and protein dataset, but enriching for genes associated with mutations significantly improved the protein–RNA correlation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Together, the results provide insight into the biology of VLBs and demonstrate the gains derived from examining the proteome in addition to genome and transcriptome.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1243-1251"},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847997","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":"Extramedullary disease in Waldenström macroglobulinemia: A population-based observational study","authors":"Simon Østergaard,&nbsp;Lars Munksgaard,&nbsp;Torsten Holm Nielsen,&nbsp;Troels Hammer,&nbsp;Lars Møller Pedersen,&nbsp;Mette Ølgod Pedersen,&nbsp;Lise Mette Rahbek Gjerdrum","doi":"10.1002/jha2.1037","DOIUrl":"10.1002/jha2.1037","url":null,"abstract":"<p>Introduction: Extramedullary disease (EMD) is a rare manifestation of Waldenström macroglobulinemia (WM), and its clinical and prognostic implications are poorly understood. Methods: In this single-center study, we investigated the clinical significance of EMD in a cohort of 469 WM patients. Results: EMD was identified in 30 (6.4%) patients, with the central nervous system, kidneys, and lungs being the most frequently affected sites. The cumulative incidence of EMD was 12.6% at 15 years. Median overall survival rates at 5 and 10 years for patients with EMD were 63% and 37%, respectively. Conclusion: Our findings indicate a persistent risk of EMD throughout the disease course, with no significant impact on long-term survival.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1269-1273"},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848564","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 UK consensus supporting effective introduction of novel treatments for multiple myeloma in the National Health Service","authors":"Rakesh Popat,&nbsp;Supratik Basu,&nbsp;Sarah Henshaw,&nbsp;Kamaraj Karunanithi,&nbsp;Karthik Ramasamy,&nbsp;Inderjit Singh,&nbsp;Anish Tailor,&nbsp;Ian Walker,&nbsp;Tim Warren,&nbsp;Noreen Ali,&nbsp;Charles Duffield,&nbsp;Gordon Cook","doi":"10.1002/jha2.1038","DOIUrl":"10.1002/jha2.1038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Multiple myeloma (MM) is a relapsing, debilitating blood cancer which remains incurable despite advances in treatments. Patients typically receive multiple lines of treatment, to which they become refractory, thereby limiting treatment options. B-cell maturation antigen (BCMA) bispecific antibodies (BsAbs) represent a novel modality of treatment that has significant efficacy for relapsed or refractory patients.</p>\u0000 \u0000 <p>The objective was to develop consensus statements for the effective implementation of BCMA BsAbs for relapsed or refractory MM patients within the National Health Service (NHS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The process employed a modified Delphi methodology. In March 2023, a literature review on the topic of novel treatments for MM was performed using the PubMed database.</p>\u0000 \u0000 <p>The process employed a modified Delphi methodology. Following a literature review, a steering group of eight expert clinicians identified and agreed on five main topics of focus and 44 statements. These were then developed into an online survey which was distributed to healthcare professionals working in Levels 1, 2 and 3 haematology centres in the United Kingdom. Results were then shared with the expert panel to determine conclusions. The threshold for consensus agreement was set at 75%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 60 responses were received from all three centre levels. There was representation from all targeted centres. Consensus was achieved in 42 statements (95%) across three broad areas: the patient profile, initiation and step-up dosing, monitoring and ongoing care, the role of multidisciplinary team and service designs for optimal management, consensus was not achieved for two statements. Given the level of agreement and that the stopping criteria were met, it was decided not to undertake further Delphi rounds.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This consensus provides a framework to support the effective introduction of novel treatments for MM in the NHS. The results were used to inform a checklist for use within haematology services when considering the provision of MM care specific to BCMA BsAbs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1133-1143"},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848254","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":"A panoply of neoplastic plasma cells","authors":"Radu Chiriac,&nbsp;Sophie Gazzo","doi":"10.1002/jha2.1010","DOIUrl":"10.1002/jha2.1010","url":null,"abstract":"&lt;p&gt;A 70-year-old man with a 5-year history of prostate adenocarcinoma, currently in complete remission, presented with pancytopenia and pain in his lower ribs. No abnormal circulating cells were observed.&lt;/p&gt;&lt;p&gt;The positron emission tomography-computed tomography (PET-CT) scan revealed fractures of the two last right ribs and abnormal F-18 fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F-FDG) uptake in the axial skeleton. A bone marrow aspirate revealed the presence of abnormal plasma cells, varying from small to medium-sized mononucleated forms to bi-, tri-, quadri-, and even pentanucleated forms, resembling anaplastic plasma cells (Figure 1, Panel A, May-Grunwald Giemsa stain, x100 objective). Flow cytometry confirmed a lambda-restricted population of CD38+/CD138+ plasma cells with loss of CD45, CD19, CD56, and CD117. Blood work showed immunoglobulin G lambda paraprotein. Metastatic adenocarcinoma was excluded by immunohistochemistry. Interphase fluorescence in situ hybridization (FISH) analysis revealed a del(17)(p13.1) involving &lt;i&gt;TP53&lt;/i&gt; (Figure 1, Panel B, TP53/NF1 deletion probe) in 95% of cells, including both diploid and tetraploid clones, and an IgH(14q32) abnormality (Figure 1, Panel C, diminished FISH signals, IGH+ break-apart probe). No t(4;14)(p16;q32) FGFR3/IGH translocation was detected. These findings were consistent with multiple myeloma displaying anaplastic features.&lt;/p&gt;&lt;p&gt;The patient, ineligible for a transplant, was started on bortezomib, cyclophosphamide, and dexamethasone. After completing four cycles with a very good partial response, he was admitted to the hospital with worsening respiratory distress and grade 4 neutropenia. A chest CT scan revealed hazy ground-glass opacities scattered throughout both lungs, with denser abnormalities in the lower lobes bilaterally. There were no other signs or symptoms suggestive of pneumonia. The patient was treated with high-dose methylprednisolone and noninvasive positive pressure ventilation for bortezomib-induced pneumonitis but showed no improvement. Unfortunately, two weeks after admission, the patient passed away due to ventilator-associated pneumonia.&lt;/p&gt;&lt;p&gt;This case highlights that while most plasma cell neoplasms are recognizable by classic morphology, some variants with unusual features can mimic anaplastic carcinoma or lymphoma. Their pleomorphic multinucleated morphology can resemble that of multinucleated carcinomas or even dysplastic megakaryocytes due to their multilobed nuclei and, abnormal nuclear distribution, complicating the differentiation from metastatic carcinoma, myelodysplastic syndrome, or plasmablastic lymphoma [&lt;span&gt;1&lt;/span&gt;]. Additionally, the patient's prior history of adenocarcinoma further challenged the diagnostic process in this case.&lt;/p&gt;&lt;p&gt;Radu Chiriac and Sophie Gazzo wrote the manuscript, conducted the cytological studies, and performed the cytogenetic studies. All authors contributed to the final manuscript.&lt;/p&gt;&lt;p&gt;The authors declare no conflicts of interest","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1342-1343"},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848497","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":"Optimization criteria for ordering myeloid neoplasm next-generation sequencing","authors":"Savanah D. Gisriel,&nbsp;John G. Howe,&nbsp;Christopher A. Tormey,&nbsp;Richard Torres,&nbsp;Karl M. Hager,&nbsp;Henry M. Rinder,&nbsp;Alexa J. Siddon","doi":"10.1002/jha2.1036","DOIUrl":"10.1002/jha2.1036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Myeloid neoplasms (MNs) frequently harbor pathogenic mutations not detected by karyotyping and fluorescence in situ hybridization; hence, next-generation sequencing (NGS) is necessary for diagnosis, risk stratification, and therapy. If, however, NGS is not clinically indicated but still performed, the results may promote futile avenues of investigation, heighten patient distress, and increase cost.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We created criteria to approve NGS testing for MN (MN-NGS) with the goal of maximizing actionable results. These actionable results include making a new MN diagnosis, characterizing a MN with baseline mutational status, and altering treatment plans. Approval criteria included clinical suspicion of new, relapsed, or worsening disease and end-of-induction chemotherapy. Cancellation criteria included the suspicion of non-myeloid disease only, no suspicion of progression of a known MN, no evidence for recurrence post-transplant, a diagnosis of chronic myeloid leukemia, and cases using blood when a concurrent bone marrow NGS is being performed. We applied these criteria to NGS tests ordered at our institution between August and December 2018 and determined whether any tests meeting our cancelation criteria yielded actionable results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Consecutive MN-NGS orders (<i>n</i> = 174) were retrospectively categorized as appropriate (Group A, <i>n</i> = 115), inappropriate (Group B, <i>n</i> = 29), and appropriately canceled (group C, <i>n</i> = 30). Seventy-five of the 115 (65%) Group A tests and none of the 29 (0%) Group B tests yielded actionable results (<i>p</i> &lt; 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Approximately one third (59/174) of MN-NGS test orders can be safely canceled using these criteria, which would result in $150,370 of Centers for Medicare and Medicaid Services-reimbursed savings annually.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1236-1242"},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848605","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":"Interleukin-6 transcripts up-regulation in lymph nodes from unicentric and multicentric Castleman disease","authors":"Marco Lucioni,&nbsp;Gaia Morello,&nbsp;Caterina Cristinelli,&nbsp;Sara Fraticelli,&nbsp;Giuseppe Neri,&nbsp;Erica Travaglino,&nbsp;Marco Minetto,&nbsp;Francesca Antoci,&nbsp;Paolo Libretti,&nbsp;Marcello Gambacorta,&nbsp;Luca Arcaini,&nbsp;Claudio Tripodo,&nbsp;Marco Paulli","doi":"10.1002/jha2.1034","DOIUrl":"10.1002/jha2.1034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Castleman disease (CD) represents a spectrum of heterogeneous lymphoproliferative disorders sharing peculiar histopathological features, clinically subdivided into unicentric CD (UCD) and multicentric CD (MCD) and presenting with variable inflammatory symptoms. Interleukin (IL)-6 and other cytokines play a major role in mediating CD inflammatory manifestations. Although the local microenvironment seems to be among the major sources of hypercytokinemia, the precise cellular origin of IL-6 production in CD is still debated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A series of five nodal CD of different subtypes (one UCD, two idiopathic MCDs [iMCDs], one HIV-negative human herpesvirus 8 (HHV8)-associated MCD, and one HIV-positive HHV8-associated MCD) and a non-CD reactive control were tested using RNAscope analysis and a dual in situ hybridization (ISH)/immunohistochemistry technique, in order to quantify IL-6 expression and its spatial distribution. Quantitative analyses of in situ mRNA were performed on digitalized slides using the HISTOQUANT software (3DHISTECH) and differences between cases were evaluated by the Kruskal-Wallis test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RNA-ISH documented increased <i>IL-6</i> expression in all CD lymph nodes, independently from clinical and pathological subtypes, however, the highest levels were found in HHV8+ cases and statistically significant differences in IL-6 expression were found only between HHV8+ MCD and control case. Dual RNA-ISH for <i>IL6</i> coupled with immunohistochemistry analysis showed that IL-6 was overexpressed in CD31-positive endothelial cells in 5/5 CD tested cases but not in the control case.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that nodal IL-6 expression seems to be significantly upregulated in HHV8+ MCD, but a trend toward increased nodal IL-6 expression was noticed also in UCD and iMCD-not otherwise specified. CD31+ endothelial cells probably represent one of the major sources of IL-6 production in the nodal microenvironment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1182-1189"},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848597","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":"Oral acute graft-versus-host disease","authors":"Farzad Teymouri,&nbsp;Gale Sebastian,&nbsp;Hakan Gem,&nbsp;Samuel S. Minot,&nbsp;Armin Rashidi","doi":"10.1002/jha2.1033","DOIUrl":"10.1002/jha2.1033","url":null,"abstract":"<p>Oral acute graft-versus-host disease (aGVHD) is rare and with no diagnostic criteria. We report a case of oral aGVHD with three clinical phases. A self-limited prodrome of largely subjective oral symptoms was followed by concurrent oral and upper gastrointestinal aGVHD. Six months after transplantation, the patient was diagnosed with severe oral and upper gastrointestinal chronic GVHD. We compared the salivary microbiota of our patient at the time of diagnosis of aGVHD with 50 contemporaneous transplant recipients and found no evidence for oral microbiota involvement in pathogenesis. This in-depth N-of-1 analysis reveals novel aspects of oral aGVHD pathogenesis.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1290-1294"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847453","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}