EJHaem最新文献

{"title":"T-Cell Receptor Repertoires Show Dynamic Variation Between Diagnosis and Relapse of Diffuse Large B-Cell Lymphoma","authors":"Joel Wight,&nbsp;Tom Witkowski,&nbsp;Colm Keane,&nbsp;Eliza A. Hawkes","doi":"10.1002/jha2.70097","DOIUrl":"https://doi.org/10.1002/jha2.70097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tumour infiltrating lymphocyte (TIL) T-cell receptor (TCR) repertoire is prognostic in newly diagnosed diffuse large B-cell lymphoma (DLBCL), but evolution has not been evaluated at relapse.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined the TCR repertoire in nine paired DLBCL samples from diagnosis and relapse.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We noted considerable differences, with dominant clones at diagnosis replaced at relapse by new clones that were absent or minor initially. There was low linearity between diagnostic and relapsed samples (<i>r</i>-values 0.01–0.316), with shared clones averaging 8.3% (range 0%–37%). Clonal diversity was reduced in relapsed samples, suggesting an increasingly defunct intratumoural immune response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>T-cell diversity is reduced in relapsed/refractory DLBCL, which may have implications for immunotherapy usage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582108","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":"Cutaneous Reactions to Iron Infusions: A Case Report and Clinical Review","authors":"Neil Patil,&nbsp;Sairekha Ravichandran,&nbsp;Jane Messina,&nbsp;Kedar Kirtane,&nbsp;Vania Phuoc,&nbsp;Timothy Kubal,&nbsp;Satish Maharaj","doi":"10.1002/jha2.70094","DOIUrl":"https://doi.org/10.1002/jha2.70094","url":null,"abstract":"<p>Anemia is prevalent globally and often treated with intravenous (IV) iron formulations, including iron sucrose, iron dextran, ferric carboxymaltose, ferric derisomaltose, and ferumoxytol. IV iron has a high efficacy and safety profile, quickly improving hemoglobin levels with low rates of adverse events. In this work, we report an uncommon case of a cutaneous hypersensitivity reaction following IV iron. A review of the literature shows that acute and delayed cutaneous reactions are possible but rare and respond well to management. Patients should be educated, and staff should be vigilant as to these cutaneous reactions.</p><p><b>Clinical Trial Registration</b>:The authors have confirmed that clinical trial registration is not needed for this submission.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573256","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":"Bleeding Complications in JAK2-Variant Essential Thrombocythemia: A Revisit in 2025","authors":"Gerard Gurumurthy,&nbsp;Samantha Gurumurthy,&nbsp;Tim C. P. Somervaille,&nbsp;Anna Falanga,&nbsp;Jecko Thachil","doi":"10.1002/jha2.70088","DOIUrl":"https://doi.org/10.1002/jha2.70088","url":null,"abstract":"<p>Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterised by sustained thrombocytosis. Paradoxically, bleeding complications remain an under-recognised clinical challenge. Compared with CALR-mutated patients, those harbouring the JAK2-V617F variant appear more prone to haemorrhage. This may be secondary to acquired von Willebrand syndrome (AvWS) and intrinsic platelet dysfunction. AvWS in ET arises from extreme platelet counts driving the adsorption and proteolysis of high-molecular-weight von Willebrand factor (VWF) multimers, producing a qualitative VWF defect akin to type 2A von Willebrand disease. However, the platelet count threshold for AvWS is variable, and patients with platelet counts below 1000 × 10⁹/L may still exhibit clinically significant VWF anomalies. Diagnosis relies on tests such as VWF activity and antigen levels. Perioperative management of patients with AvWS focuses on correcting the VWF defect and/or lowering platelet counts. Ultimately, clinicians must balance between preventing thrombosis and bleeding by tailoring management to each patient.</p><p><b>Clinical Trail Registration</b>The authors have confirmed clinical trial registration is not needed for this submission.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551016","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":"Serum Ferritin in Women With HFE p.C282Y Homozygosity: Positive Associations With Age, Live Births, Menopause, and Transferrin Saturation","authors":"James C. Barton,&nbsp;J. Clayborn Barton,&nbsp;Ronald T. Acton","doi":"10.1002/jha2.70092","DOIUrl":"https://doi.org/10.1002/jha2.70092","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We sought to determine associations of serum ferritin (SF) with live birth numbers and other iron-related variables in women with <i>HFE</i> p.C282Y (rs1800562) homozygosity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied non-pregnant, non-Hispanic white women in post-screening evaluations to determine associations of SF with age, pregnancy and live birth numbers, dichotomous menopause and therapeutic phlebotomy reports, daily food and supplemental iron intakes, and transferrin saturation (TS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 136 women with mean age 51 ± 13 (SD) years and median SF 238 µg/L (range: 8, 2960). There were 376 pregnancies (median: 3/woman (1, 8)) and 296 live births (median: 2/woman (0, 6)). A total of 70 women (51.5%) reported menopause and 31 women (22.8%) reported phlebotomy. Median heme + non-heme food iron intake was 13.4 mg/d (3.1, 57.3). Mean TS was 62 ± 25%. Pearson's coefficient of ln SF versus age was 0.1955 (<i>p</i> = 0.0226). Median SF of women with and without menopause was 386 µg/L (8, 2960) and 165 µg/L (8, 1894), respectively (<i>p</i> &lt; 0.0002). SF associations with phlebotomy and iron intakes were not significant. Spearman's coefficient of SF versus TS was 0.5079 (<i>p</i> &lt; 0.0001). Four mean ln SF values of 66 women without menopause subgrouped by live birth numbers were similar (one-way ANOVA <i>p</i> = 0.4460). Multiple regressions on SF using pregnancy numbers revealed positive associations with menopause (<i>p</i> = 0.0157) and TS (<i>p</i> &lt; 0.0001) and using live birth numbers revealed positive associations with live births (<i>p</i> = 0.0389), menopause (<i>p</i> = 0.0305), and TS (<i>p</i> &lt; 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SF levels in 136 women with p.C282Y homozygosity are positively associated with age, numbers of live births, menopause reports and TS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524920","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 Real World Impact of Immunoglobulin Replacement Therapy on Severe Bacterial Infection for Patients With Hypogammaglobulinemia Secondary to Hematologic Malignancies: A Japanese Claims Database Study","authors":"Keichiro Mihara,&nbsp;Takakazu Kawase,&nbsp;Takahiko Miyama,&nbsp;Katsuhiko Iwasaki,&nbsp;Ayako Shoji,&nbsp;Masayuki Matsumaru","doi":"10.1002/jha2.70091","DOIUrl":"https://doi.org/10.1002/jha2.70091","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The understanding of usefulness of immunoglobulin replacement therapy (IgRT) for hypogammaglobulinemia (HGG) in patients with hematologic malignancies (HM) has changed over time. This is mainly caused by the introduction of new treatment, such as B-cell targeted agents. We investigated the real world effectiveness of IgRT on the severe bacterial infection (SBI) incidence in patients with HGG secondary to HMs using a Japanese claims database provided by MDV Inc.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients who were diagnosed with both HM and HGG from May 2010 to March 2021 in this database and prescribed IgRT with the dosage of &gt; 5 g/month were eligible. We compared the SBI incidence, which was defined as a prescription of intravenous antibacterial agents during hospitalization, between during 12-month before IgRT initiation (baseline period) and 12-month after IgRT initiation (follow-up period).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total 1621 eligible patients, 37.9% and 17.7% of patients were for non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM), respectively. A total of 24.4% of patients were hematopoietic stem cell transplantation (HSCT) recipients. In the follow-up period, SBI incidence significantly decreased than that in the baseline period (2.3 events per person-year vs. 0.9; <i>p</i> &lt; 0.001). Similar results were observed in various subgroups such as patients who were diagnosed with NHL or MM, treated with anti-CD20 monoclonal antibody or anti-CD38 monoclonal antibody, or HSCT recipients. In the small number of patients whose baseline serum IgG levels were available (<i>n</i> = 28), decrease of the SBI incidence in the follow-up period was observed regardless of IgG levels. A reduction of the SBI incidence was seen in patients with &lt; 400 mg/dL (2.6 vs. 0.6).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IgRT may decrease the SBI incidence in patients with HGG secondary to HM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration:</h3>\u0000 \u0000 <p>Registered at UMIN Clinical Trials Registry, UMIN000047418</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524921","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":"Gallbladder Myeloid Sarcoma Associated With NPM1 Mutated Acute Myeloid Leukemia","authors":"Francesco Grimaldi,&nbsp;Maria Gabriella Rascato,&nbsp;Pier Paolo Mainenti,&nbsp;Marcella Giordano,&nbsp;Massimo Mascolo,&nbsp;Fabrizio Pane","doi":"10.1002/jha2.70086","DOIUrl":"https://doi.org/10.1002/jha2.70086","url":null,"abstract":"&lt;p&gt;According to the 2022 World Health Organization (WHO) [&lt;span&gt;1&lt;/span&gt;] and International Consensus Classification (ICC) [&lt;span&gt;2&lt;/span&gt;] of myeloid neoplasm, myeloid sarcoma (MS) is a de novo disease characterized by extramedullary infiltration of immature myeloid precursors, that may accompany peripheral blood and marrow involvement of acute myeloid leukemia (AML), or present as relapse or as progression to AML of a prior myeloproliferative or myelodysplastic disorder. Diagnosis of MS is rare, and affects approximately 2%–10% of AML patients [&lt;span&gt;3&lt;/span&gt;], with common sites including skin, lymph nodes, bones, and soft tissues [&lt;span&gt;4&lt;/span&gt;]. Most of the cases present with a monoblastic or myelomonocytic infiltration [&lt;span&gt;5&lt;/span&gt;], are associated with chromosomal abnormalities like t8;21, trisomy 8, or chromosome 7 partial or complete deletion [&lt;span&gt;5&lt;/span&gt;], and can show recurrent mutations in &lt;i&gt;NPM1&lt;/i&gt;, &lt;i&gt;FLT3&lt;/i&gt;, and &lt;i&gt;N-RAS&lt;/i&gt; genes [&lt;span&gt;6&lt;/span&gt;]. MS gastrointestinal involvement [&lt;span&gt;4, 7&lt;/span&gt;] is less frequent (∼10%), predominantly affects the small or large intestine, and generally presents with symptoms like abdominal pain or bowel obstruction.&lt;/p&gt;&lt;p&gt;Herein, we describe an unusual case of gallbladder infiltration by MS in an elderly AML patient. An 81-year-old male was admitted to our clinic for AML with hyperleukocytosis (WBC 100,000/mm&lt;sup&gt;3&lt;/sup&gt;, Hb 12.3 g/dL, and PLT 59,000/mm&lt;sup&gt;3&lt;/sup&gt;). Bone marrow flow cytometry demonstrated 83% monocytic blasts (CD34−, CD117−, CD33+, CD13+, CD14+/−, CD64+, CD36+, CD4+, and CD56+). Standard cytogenetic with fluorescence in situ hybridization analysis revealed a normal karyotype, while next-generation sequencing identified &lt;i&gt;ASXL1&lt;/i&gt;, &lt;i&gt;SRSF2&lt;/i&gt;, and &lt;i&gt;NPM1&lt;/i&gt; type A mutations. A final diagnosis of AML with defining genetic abnormalities was done following the 2022 WHO criteria [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Given advanced age and low-performance status, cytoreduction with hydroxyurea followed by decitabine [&lt;span&gt;8&lt;/span&gt;] (5-day schedule) was started. However, on day +20 patient developed fever (38.6°C), right upper quadrant abdominal pain, nausea, and elevation of alanine transaminase, gamma-glutamyl-transpeptidase, and alkaline phosphatase liver enzymes. Abdominal computed tomography showed a distended gallbladder with infundibular gallstones and possible choledocholithiasis. Supportive treatment, including hydration, fasting, and intravenous antibiotics (amikacin and tigecycline), was initiated. However, the patient's clinical condition rapidly deteriorated, prompting further evaluation.&lt;/p&gt;&lt;p&gt;Magnetic resonance cholangiopancreatography revealed a &lt;1 cm common bile duct stone, mild biliary dilatation, and gallbladder wall thickening (Figure 1a). Laparoscopic cholecystectomy combined with endoscopic retrograde cholangiopancreatography for bile duct clearance was performed, resulting in fast clinical and biochemical improvement. Unexpectedly, histopathological examin","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515115","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":"Peripheral Multilineage Haemophagocytosis in an Extremely Premature Infant With Escherichia coli Sepsis","authors":"Jorik H. Amesz,&nbsp;Richard M. Noordervliet,&nbsp;Madeleen Bosma","doi":"10.1002/jha2.70090","DOIUrl":"https://doi.org/10.1002/jha2.70090","url":null,"abstract":"<p>An extremely premature girl was born following spontaneous labour at 24 weeks of gestation. The mother's urine culture revealed a resistant strain of <i>Escherichia coli</i>. The neonate was intubated due to respiratory insufficiency, and intermittent phototherapy was initiated. One week postpartum, the infant's blood culture yielded a positive result for <i>Staphylococcus aureus</i> infection, most likely attributed to a line-associated bloodstream infection. Consequently, antibiotic therapy with flucloxacillin and gentamicin was started. A week later, C-reactive protein levels rose to 81.1 mg/L, the girl developed circulatory insufficiency, and blood appeared in the endotracheal tube. Haematological analysis showed thrombocytopenia (83 × 10⁹/L), anaemia (4.7 mmol/L), and leucocytosis (25 × 10⁹/L). Microscopic evaluation revealed erythrophagocytosis, thrombophagocytosis, lymphophagocytosis and intra- and extra-cellular bacteria in the peripheral smear (May–Grünwald Giemsa stain, magnification ×400) (Figure 1). Additionally, vacuolation and toxic granulation was present in ≥50% of neutrophils. Direct antiglobulin tests were negative. Antibiotic therapy was switched to meropenem, which improved the girl's condition. Haemophagocytosis was not observed on subsequent smears. The blood culture was positive for <i>E. coli</i> infection only 2 days later.</p><p>Haemophagocytosis in the peripheral blood is rare, particularly in neonates, but it is an important diagnostic clue [<span>1</span>]. It is most commonly associated with haemolytic disease of the newborn, but can also be triggered by severe infections, such as bacterial sepsis, viral infections, and fungal or parasitic diseases [<span>2</span>]. In this case, the presence of <i>E. coli</i> likely triggered a hyperinflammatory response, leading to the observed erythro-, thrombo-, and lymphophagocytosis in the peripheral smear [<span>3</span>]. The finding of intracellular bacteria in blood smears is concerning, as it may indicate overwhelming infection [<span>4</span>], requiring urgent intervention. Timely recognition of haemophagocytosis and bacterial presence on blood smears can be lifesaving, especially given the limited material available for laboratory analysis in neonates. Once the underlying infection is brought under control, the haemophagocytic activity typically subsides.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515116","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":"Aggressive Myeloid Sarcoma Mimicking Burkitt's Lymphoma","authors":"Eman Hassan,&nbsp;Syed Aaquil Hasan,&nbsp;Samer Abbas,&nbsp;Peter Dyer,&nbsp;Hayder Hussein","doi":"10.1002/jha2.70089","DOIUrl":"https://doi.org/10.1002/jha2.70089","url":null,"abstract":"&lt;p&gt;A 68-year-old female presented with a two-month history of weight loss and back pain. Apart from mild anaemia (haemoglobin 9.8 g/dL) and high lactate dehydrogenase (LDH) 1618 U/L, all other blood investigations were otherwise normal. An initial CT scan of the abdomen and pelvis revealed extensive para-aortic, and mesenteric lymphadenopathy (Figure 1). A biopsy of the para-aortic lymph node demonstrated poorly differentiated malignancy. The initial panel of immunohistochemical markers was negative for tumour characterization. Further immunohistochemistry revealed CD117 and CD43 positivity in the tumour cells, raising the possibility of myeloid differentiation. However, a myeloid malignancy was considered unlikely due to the absence of expression of myeloperoxidase (MPO) and common leucocytic antigen (LCA), CD68, terminal deoxynucleotidyl transferase (TdT), CD15 or CD56.&lt;/p&gt;&lt;p&gt;The absence of definitive lineage markers raised suspicion for a high-grade, aggressive malignancy. However, due to the inconclusive immunophenotype, treatment was deferred, and a repeat biopsy was planned. A total of 5 weeks later, while awaiting further immunohistochemistry, the patient's condition deteriorated with worsening abdominal pain. A repeat CT scan revealed (Figure 2) new findings of ascites, a gallbladder mass, bilateral hydronephrosis and a moderate-sized right pleural effusion. Cytospin of pleural fluid showed large vacuolated blasts with a morphology resembling Burkitt-like cells (Figure 3). Flow cytometry of the blasts revealed CD45 negativity, raising suspicion for a non-haematological malignancy. A screen for abnormal B or T lymphoid populations was negative.&lt;/p&gt;&lt;p&gt;An acute myeloid leukaemia (AML) panel showed ∼97.6% myeloid cells (CD33+ and/or CD13+) with reduced expression of CD11b+. 5.3% of cells were CD14+, and 66% of blasts were CD45 negative, CD34+, CD117+, HLA-DR weak, CD38+ and CLL1+. This blast population was negative for CD3, CD4, CD7, CD19, CD30, CD56, CD123, MPO, cytoplasmic CD3, CD22 and CD79a. These findings were consistent with a diagnosis of AML. Blastic plasmacytoid dendritic cell neoplasm and systemic mastocytosis were considered; however, the absence of CD123 expression and lack of morphological features of mastocytosis made these diagnoses unlikely. Molecular studies were not performed on the available samples, and obtaining a new sample was deemed impractical due to the patient's clinical deterioration. The bone marrow aspirate findings showed no evidence of malignancy, and the diagnosis of myeloid sarcoma was subsequently established. The patient started on intensive chemotherapy. However, within days of treatment, she developed tumour lysis syndrome, which required haemodialysis. Unfortunately, the patient deteriorated further due to sepsis and passed away shortly after commencing treatment. This case highlights the diagnostic complexity of myeloid sarcoma, which can mimic lymphoma in its clinical and morphological presentation.&lt;/p","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492651","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":"Clinical Significance of Elevated Levels of Soluble-Form Immune Checkpoint Molecules in Patients With Aggressive Adult T-Cell Leukemia-Lymphoma","authors":"Shigeo Fuji,&nbsp;Junya Makiyama,&nbsp;Kuniko Takano,&nbsp;Ilseung Choi,&nbsp;Takeo Suzuki,&nbsp;Chihiro Suminaka,&nbsp;Mao Kuroishi,&nbsp;Yosuke Iwasaki,&nbsp;Hidenori Kasahara,&nbsp;Yuma Tada,&nbsp;Yasuhiro Shingai,&nbsp;Sayako Yuda,&nbsp;Takafumi Yokota,&nbsp;Jun Ishikawa","doi":"10.1002/jha2.70046","DOIUrl":"https://doi.org/10.1002/jha2.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Immune checkpoint (IC) pathways, including programmed death protein 1 (PD-1), its ligand PD-L1, and CTLA-4, mediate negative regulatory signals in immune responses. Recent studies in autoimmune diseases and malignancies reported that the presence of the soluble form of these ICs would reflect the overall immune status. We assessed the clinical significance of these soluble-form ICs in HTLV-1 carriers and adult T-cell leukemia-lymphoma (ATL) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>After obtaining informed consent, plasma from HTLV-1 carriers and ATL patients was prospectively collected in participating centers. Plasma concentrations of soluble-form PD-1, PD-L1, and CTLA-4 (sPD-1, sPD-L1, and sCTLA-4) were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ninety-six cases were included (HTLV-1 carriers, <i>n</i> = 4; indolent ATL, <i>n</i> = 14; aggressive ATL, <i>n</i> = 78). The median age at sampling was 65.5 (range, 23–85) years. Soluble factors levels were significantly higher in aggressive ATL than in indolent ATL (sPD-1, <i>p</i> = 0.003; sPD-L1, <i>p</i> = 0.017; sCTLA-4, <i>p</i> &lt; 0.001). These markers were strongly correlated with soluble IL-2R (sPD-1, <i>r</i> = 0.80; sPD-L1, <i>r</i> = 0.61; sCTLA-4, <i>r</i> = 0.82). Elevated soluble IC levels were significant adverse prognostic factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Soluble IC levels were significantly higher in aggressive ATL than in indolent ATL, and predicted an adverse prognosis. Their clinical significance should be investigated in larger studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492652","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":"Next Generation Sequencing Allows Identification of a Novel Mutation in the TfR2 Gene and Outperforms the Conventional Diagnostic Techniques","authors":"Miriam Longo,&nbsp;Erika Paolini,&nbsp;Marica Meroni,&nbsp;Felice Cinque,&nbsp;Cristina Bertelli,&nbsp;Giuseppina Pisano,&nbsp;Marco Maggioni,&nbsp;Anna Ludovica Fracanzani,&nbsp;Rosa Lombardi,&nbsp;Paola Dongiovanni","doi":"10.1002/jha2.70073","DOIUrl":"https://doi.org/10.1002/jha2.70073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Type 3 hereditary hemochromatosis (HH) is a rare genetic disease due to mutations in the transferrin receptor 2 (<i>TFR2</i>) gene.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Here, we describe the case of an Italian patient presenting with hyperferritinemia and hepatic iron accumulation, not evidenced by magnetic resonance imaging, that was subsequently classified as HH Type 3 by the identification of the novel frameshift mutation c.523_524delC&gt;T (p. Leu175Aspfs*41) in exon 4 of <i>TFR2</i> gene through the whole exome sequencing (WES) approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>WES would allow to diagnose rare HH-related diseases in patients with unexplained hepatic iron overload and/or aberrant circulating iron parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The authors have confirmed clinical trial registration is not needed for this submission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482284","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}