EJHaem最新文献

{"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}

{"title":"Rapid high-dose cyclophosphamide as bridging treatment for advanced therapies in multiple myeloma","authors":"Marcus Marable,&nbsp;Kaitlin Kelly,&nbsp;Jennifer H. Cooperrider,&nbsp;Andrzej Jakubowiak,&nbsp;Benjamin A. Derman","doi":"10.1002/jha2.1039","DOIUrl":"10.1002/jha2.1039","url":null,"abstract":"<p>Patients with relapsed/refractory multiple myeloma proceeding with chimeric antigen receptor (CAR) T-cell therapy or bispecific antibodies (BsAb) may need bridging therapy to realize their benefits. We evaluated the efficacy and safety of rapid, peripheral, high-dose cyclophosphamide (TurboCy) in 15 patients intending to proceed with CAR T-cell therapy, BsAbs, or long-term regimens. The overall response rate was 80% and the clinical benefit rate was 100% in a heavily pretreated high-risk cohort. Cytopenias were common but no deaths occurred during bridging. All patients proceeded to their next line of intended therapy. TurboCy is an effective and safe bridging strategy.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1260-1264"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848158","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":"Cyclin D1-negative and SOX11-positive B-cell lymphoma with CD5 and CD10 coexpression and MYC rearrangement: A diagnostic challenge","authors":"Mingfei Yan,&nbsp;Yanming Zhang,&nbsp;Ahmet Dogan,&nbsp;Mariko Yabe","doi":"10.1002/jha2.1040","DOIUrl":"10.1002/jha2.1040","url":null,"abstract":"&lt;p&gt;A 66-year-old male presented with a large left renal/perirenal mass (9.7 cm) and diffuse lymphadenopathies. A biopsy showed diffuse proliferation of monotonous small to intermediate lymphocytes with irregular nuclei and condensed chromatin (upper left, 20×; upper middle, 400×). The background epithelioid histiocytes and hyalinized vessels were noted. By immunohistochemistry, the lymphocytes were positive for CD20, CD5 (upper right, 200×), CD10 (middle left, 200×), SOX11 (middle central, 200×), and BCL2, but were negative for cyclin D1 (middle right, 200×), cyclin D3, CD23, and BCL6. MYC was expressed by 10%–20% of the cells with heterogeneous intensities (lower left, 200×), and the Ki67 proliferation index was about 30% (lower middle, 200×). Cytogenetic studies revealed &lt;i&gt;MYC&lt;/i&gt; rearrangement in 97% of cells by using &lt;i&gt;MYC&lt;/i&gt; break-apart probes (lower right, 5′ probe in red, 3′ probe in green) but with no evidence of &lt;i&gt;IGH::MYC&lt;/i&gt;, &lt;i&gt;IGK::MYC&lt;/i&gt;, or &lt;i&gt;IGL::MYC&lt;/i&gt; fusions by further evaluation by fluorescence in situ hybridization (FISH). Assessment for rearrangements by using &lt;i&gt;CCND1&lt;/i&gt;, &lt;i&gt;CCND2&lt;/i&gt;, &lt;i&gt;CCND3&lt;/i&gt;, &lt;i&gt;BCL2&lt;/i&gt;, &lt;i&gt;BCL6&lt;/i&gt;, and &lt;i&gt;IGH&lt;/i&gt; break-apart probes were all negative.&lt;/p&gt;&lt;p&gt;Based on the morphological and immunophenotypical features, this most likely represents a cyclin D1-negative mantle cell lymphoma with &lt;i&gt;MYC&lt;/i&gt; rearrangement. SOX11 is a highly specific marker for mantle cell lymphomas, which is consistently negative in other mature B-cell lymphomas other than Burkitt lymphoma [&lt;span&gt;1&lt;/span&gt;]. However, we were not able to demonstrate the presence of &lt;i&gt;CCND1/2/3&lt;/i&gt; rearrangements by break-apart FISH probes. It has been reported that cryptic insertions of immunoglobulin (IG) light chain enhancers are associated with cyclin D2/3 overexpression in cyclin D1-negative mantle cell lymphomas. Although cyclin D3 was not overexpressed in our case, cyclin D2 immunohistochemistry was not available and its overexpression cannot be excluded. In addition, a minor subset of mantle cell lymphomas lacks &lt;i&gt;CCND1/2/3&lt;/i&gt; rearrangements but instead shows cyclin E upregulation [&lt;span&gt;2&lt;/span&gt;]. &lt;i&gt;MYC&lt;/i&gt; rearrangement can be seen in about 1.5% of mantle cell lymphomas, which is associated with blastoid morphology, aggressive disease course, and CD10 expression (seen in our case) [&lt;span&gt;3&lt;/span&gt;]. To date, all the reported &lt;i&gt;MYC&lt;/i&gt;-rearranged mantle cell lymphoma cases are positive for cyclin D1 by immunohistochemistry. In our case, the lack of cyclin D1/3 expression and &lt;i&gt;CCND1/2/3&lt;/i&gt; rearrangements by break-apart FISH probes, in conjunction with the aberrant CD10 expression, confers diagnostic challenge. In addition, &lt;i&gt;MYC&lt;/i&gt; showed rearrangement with a non-IG partner gene in this case. The translocation partners in &lt;i&gt;MYC&lt;/i&gt;-rearranged mantle cell lymphomas are not well characterized. It remains to be explored whether the aggressive features associated with &lt;i&gt;MYC&lt;/i&gt;-rearranged mantle cell lymphomas are prefe","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1348-1350"},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848487","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 prognostic impact of C-reactive protein and albumin in patients diagnosed with acute myeloid leukaemia","authors":"Espen Talseth Skar,&nbsp;Øystein Wendelbo,&nbsp;Håkon Reikvam","doi":"10.1002/jha2.1022","DOIUrl":"10.1002/jha2.1022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute myeloid leukaemia (AML) is an aggressive and heterogeneous malignant disease. Patient age, comorbidities and disease-specific genetic abnormalities are recognized as primary determinants of treatment response. Recent years have elucidated the significance of nutritional status and inflammation across various malignancies, including AML, in influencing treatment outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To assess the prognostic value of the C-reactive protein-albumin ratio (CAR) and the Glasgow Prognostic Score (GPS) in predicting overall survival (OS) rates among patients diagnosed with AML.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and methods</h3>\u0000 \u0000 <p>189 AML patients receiving standard cytarabine and anthracycline-based induction treatment were included. Baseline demographic, clinical and laboratory data were collected, and treatment outcomes and survival were registered for all patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant association between CAR and prognosis among AML patients was found, even in subgroup analyses. Hypoalbuminemia was an independent predictor of poor survival among all patients (OS 28 vs. 16 months; <i>p</i> &lt; 0.02). Patients with a GPS of 0 or 1 demonstrated superior OS compared to those with a GPS of 2 (median OS 28 vs. 16 months, respectively; <i>p</i> = 0.015). Results remained consistent among patients ≥ 60 years (median OS 15 vs. 6 months; <i>p</i> = 0.020).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Heightened inflammation and suboptimal nutritional status correlate with unfavourable prognoses in AML patients. Such insights hold the potential for guiding clinical decision-making, offering easily accessible prognostic information for the induction treatment of eligible AML patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1223-1235"},"PeriodicalIF":0.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848251","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}