EJHaem最新文献

{"title":"Comprehensive Genetic Analysis of Central Nervous System Involvement in Mycosis Fungoides: A Case Report","authors":"Yasumasa Nakata,&nbsp;Fumihiko Ouchi,&nbsp;Kota Yoshifuji,&nbsp;Daichi Sadato,&nbsp;Kouhei Yamamoto,&nbsp;Yuriko Kawase,&nbsp;Takehiko Mori","doi":"10.1002/jha2.70118","DOIUrl":"https://doi.org/10.1002/jha2.70118","url":null,"abstract":"<p>The incidence of central nervous system (CNS) involvement in mycosis fungoides (MF) is low. Here, we report a case of CNS involvement 3 years after MF diagnosis, comparing genetic alterations identified by amplicon-based targeted sequencing between a primary skin sample and a brain tissue sample. <i>TNFAIP3</i> mutation, <i>MYC</i> gain, <i>CDKN2A</i>/<i>B</i> loss, and <i>SOCS1</i> loss were concordantly detected, while <i>MYC</i> mutation was only found in the brain sample. This is the first report of a comprehensive genetic analysis of CNS involvement in MF, providing novel insights into genetic factors potentially associated with CNS involvement.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751579","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":"Prognostic Value of Geriatric Characteristics in Allogeneic Haematopoietic Stem Cell Transplant Recipients Aged Over 60 Years","authors":"Xiu Hue Lee,&nbsp;Chieh Hwee Ang,&nbsp;Tertius Tansloan Tuy,&nbsp;Jeffrey Kim Siang Quek,&nbsp;Hein Than,&nbsp;Francesca Lorraine Wei Inng Lim,&nbsp;Yeow Tee Goh,&nbsp;Yeh Ching Linn,&nbsp;William Ying Khee Hwang,&nbsp;Aloysius Yew Leng Ho,&nbsp;Lawrence Cheng Kiat Ng","doi":"10.1002/jha2.70115","DOIUrl":"https://doi.org/10.1002/jha2.70115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Allogeneic haematopoietic stem cell transplant (alloHSCT) offers a curative option for older adults with haematological malignancies. The use of geriatric assessments has transformed the landscape of haemato-oncology care by improving risk stratification. We aim to study the prognostic value of geriatric characteristics in patients aged ≥ 60 years who underwent alloHSCT at Singapore General Hospital between 2017 and 2023. Patient data were examined retrospectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 66 patients were included, with a median age of 65 years and 42% aged above 65. Most patients had acute leukaemia (61%), and stem cell sources included matched sibling donor (18%), matched unrelated donor (33%) and haploidentical donor (48%). Karnofsky Performance Status (KPS) was ≥ 90 in 41% of patients, and 86% had Haematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) scores of 0–2. The median Cumulative Illness Rating Scale-Geriatric (CIRS-G) score was 5. A total of 12% had renal insufficiency.</p>\u0000 \u0000 <p>At a median follow-up of 32.5 months, 2-year non-relapse mortality (NRM), progression-free survival and overall survival (OS) were 21%, 55% and 58%, respectively. On multivariate analysis, age &gt; 65 years (HR 3.84, <i>p</i> = 0.027) and renal insufficiency (HR 6.28, <i>p</i> = 0.005) were associated with increased risks of NRM. Similarly, age &gt; 65 years (HR 2.75, <i>p</i> = 0.03) and renal insufficiency (HR 3.46, <i>p</i> = 0.01) conferred inferior OS. KPS, HCT-CI, CIRS-G, albumin, body mass index and polypharmacy did not predict for NRM and OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study supports the feasibility of alloHSCT as a treatment option for older adults with haematological malignancies. Prospective studies incorporating geriatric assessment will allow personalised transplant strategies to improve post-transplant outcomes.</p>\u0000 \u0000 <p><b>Trial Registration</b>: 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":1.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751578","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 Identification of DUX4::IGH Fusion in Acute Lymphoblastic Leukemia","authors":"Kyoko Moritani,&nbsp;Minenori Eguchi-Ishimae,&nbsp;Mari Tezuka-Kagajo,&nbsp;Machiko Miyamoto,&nbsp;Mayumi Iwamoto,&nbsp;Sanae Kawakami,&nbsp;Ryota Nakamura,&nbsp;Kozo Nagai,&nbsp;Sawa Tomomatsu,&nbsp;Tsuyoshi Imai,&nbsp;Yasushi Ishida,&nbsp;Hisamichi Tauchi,&nbsp;Eiichi Ishii,&nbsp;Mariko Eguchi","doi":"10.1002/jha2.70099","DOIUrl":"https://doi.org/10.1002/jha2.70099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p><i>DUX4</i> is rearranged and overexpressed in a subgroup of acute lymphoblastic leukemia (ALL) with B-precursor phenotype, with a favorable outcome. Even though characteristic gene expression signature as well as surface expression of CD2/CD371 could be a hallmark of <i>DUX4</i>-rearranged ALL, actual detection of <i>DUX4</i> rearrangement is, however, largely dependent on whole transcriptome analysis due to the highly repetitive nature of <i>DUX4</i> gene loci and insertion as the main mechanism of fusion gene formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Polymerase chain reactions (PCRs) with several combinations of multiplex primers located on <i>DUX4</i> and <i>IGH</i> gene loci were used for the detection of <i>DUX4::IGH</i>, which represents more than 90% of <i>DUX4</i> fusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>DUX4::IGH</i> fusion was successfully detected in three out of 50 ALL cases analyzed by standard PCR, and these positive cases showed variable insertion of <i>DUX4</i> into the <i>IGH</i> locus. In all patients, sequences of unknown origin were observed at the junction of <i>DUX4</i> and <i>IGH</i> sequences, indicating the role of the V(D)J recombination mechanism in fusion gene formation. Although <i>DUX4</i> is tandemly repeated at its locus, only a single copy of the <i>DUX4</i> sequence was detected at the <i>IGH</i> locus in two of the three <i>DUX4</i>-rearranged ALL cases. As previously reported, both CD2 and CD371 were positive in all cases with <i>DUX4</i>::<i>IGH</i> fusion, suggesting that the combination of CD2 and CD371 could be a more reliable marker for detecting the presence of this fusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Identification of <i>DUX4</i>::<i>IGH</i> fusion in ALL could be possible more easily by a simple multiplex PCR strategy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716648","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 Intersection of Lynch Syndrome and Hematological Malignancies: A Rare Short Report","authors":"Tomomi Oka,&nbsp;Takeshi Nakajima,&nbsp;Makoto Iwasaki,&nbsp;June Takeda,&nbsp;Masako Torishima,&nbsp;Maki Sakurada,&nbsp;Takuya Shimizu,&nbsp;Takero Shindo,&nbsp;Masakazu Fujimoto,&nbsp;Shinya Otsuki,&nbsp;Hironori Haga,&nbsp;Kokichi Sugano,&nbsp;Miho Ando,&nbsp;Chisaki Mizumoto,&nbsp;Junya Kanda,&nbsp;Yasuhito Nannya,&nbsp;Seishi Ogawa,&nbsp;Akifumi Takaori-Kondo,&nbsp;Shinji Kosugi","doi":"10.1002/jha2.70116","DOIUrl":"https://doi.org/10.1002/jha2.70116","url":null,"abstract":"<p>Lynch syndrome (LS), which is an autosomal dominant disorder caused primarily by germline pathogenic variants of mismatch repair (MMR) genes, cases a number of malignancies. Hematologic malignancies are not included as related tumors of LS because it has not yet been established whether the carcinogenesis of hematologic malignancies is associated with MMR genes.</p><p>A 75-year-old woman was admitted to our hospital with acute myeloid leukemia (AML) that had progressed from myelodysplastic syndrome (MDS). She had a history of multiple myeloma (MM) and multiple tumors associated with LS. Genetic testing revealed extensive homozygous deletions ranging from Exon 9 of <i>EPCAM</i> to Exons 1–6 of <i>MSH2</i>. Finally, we diagnosed her with LS. It revealed that the <i>MSH2</i> homo-deletion occurred in myeloid cells after the onset of MM. Immunohistochemistry for MMR proteins on bone marrow specimens at MDS showed the loss of staining for the MSH2 and MSH6 proteins in myeloid cells. However, microsatellite instability was negative in spite of the large homozygous deletion of <i>MSH2</i>.</p><p>It remains unclear whether the homo-deletion of <i>MSH2</i> is involved in the development of MDS/AML. Future studies are warranted to confirm the impact of MMR variants on the pathogenesis/chemoresistance of myeloid neoplasms.</p><p>Trial Registration: 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":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716974","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":"Intersecting Anemias: PARP Inhibitor-Induced Toxicity and Autoimmune Hemolysis—A Case Report","authors":"Julien Dereme,&nbsp;Konstantinos Asonitis,&nbsp;Francesco Grandoni,&nbsp;Aikaterini Liapi,&nbsp;Apostolos Sarivalasis,&nbsp;Gerasimos Tsilimidos","doi":"10.1002/jha2.70112","DOIUrl":"https://doi.org/10.1002/jha2.70112","url":null,"abstract":"<p>We present a case of a 71-year-old woman with a history of high-grade serous ovarian adenocarcinoma, treated with neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy. A maintenance treatment combining bevacizumab and olaparib was introduced consecutively. Bevacizumab was stopped 7 months later due to neurological complications. The patient developed severe, progressive anemia, leading to significant clinical management challenges, with hemoglobin levels as low as 54 g/L. Despite initially adapting and finally discontinuing olaparib, the patient remained transfusion dependent, without notable improvement. Common causes of anemia, such as iron deficiency, vitamin deficiency, autoimmune and infectious causes, were ruled out. Bone marrow biopsies revealed a clonal cytotoxic T-LGL population and a DNMT3A mutation without evidence of myelodysplasia or metastatic infiltration. A further decline in reticulocytes and the appearance of warm autoantibodies (IgG) indicated an increasingly mixed anemia profile. High-dose corticosteroids resulted in rapid hematological improvement. This case highlights a severe anemia of mixed origin with central hypo-regenerative components due to prolonged PARP inhibitor toxicity and a hemolytic mechanism associated with warm autoantibodies. The prolonged toxic effect of olaparib, in conjunction with confounding factors (DNMT3A mutation, warm autoantibodies, T-LGL clone), underscores the need for a comprehensive hematological assessment. The patient's response emphasizes the complexity of managing drug-induced hematologic toxicity and the potential for overlapping hematologic conditions.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716973","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":"Physician Survey on the Management of Pulmonary Embolism in Pregnancy: Need for Guidance and Training","authors":"Giulia Simini,&nbsp;Richard Buka,&nbsp;Daniel Kajita,&nbsp;Omar Mukhlif,&nbsp;HaemSTAR collaborators,&nbsp;Gill Swallow,&nbsp;Pip Nicolson,&nbsp;Sajida Kazi","doi":"10.1002/jha2.70113","DOIUrl":"https://doi.org/10.1002/jha2.70113","url":null,"abstract":"&lt;p&gt;The Confidential Enquiry into Maternal Deaths has consistently identified thrombosis and thromboembolism as the leading causes of direct maternal mortality in the UK and Ireland between 2013 and 2023 [&lt;span&gt;1&lt;/span&gt;]. Among these, high-risk pulmonary embolism (PE)—previously referred to as &lt;i&gt;massive PE&lt;/i&gt;—is characterized by hemodynamic instability due to obstruction of the pulmonary arterial circulation and represents a particularly critical scenario, with mortality rates as high as 37% [&lt;span&gt;2&lt;/span&gt;]. Intermediate-high risk PE, formerly known as &lt;i&gt;submassive PE&lt;/i&gt;, also carries a significant mortality risk of up to 10% [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Systemic thrombolysis remains one of the most effective treatments for high-risk PE [&lt;span&gt;4, 5&lt;/span&gt;]. However, in pregnancy, its use is fraught with significant risks, most notably the potential for life-threatening uterine hemorrhage [&lt;span&gt;6&lt;/span&gt;]. In recent years, alternative advanced reperfusion options, including catheter-directed thrombolysis (CDT), endovascular thrombectomy, and surgical thrombectomy have emerged as alternative options [&lt;span&gt;7-10&lt;/span&gt;]. While these approaches show great promise, they lack validation from large randomized controlled trials [&lt;span&gt;11&lt;/span&gt;]. Approaches to management of intermediate risk PE are less clearly defined [&lt;span&gt;12&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Efforts to bridge this evidence gap are underway: the International Society on Thrombosis and Haemostasis launched a global registry in 2019 to collect data on high-risk PE management during pregnancy and puerperium [&lt;span&gt;13&lt;/span&gt;]. Registries are invaluable for identifying trends and improving understanding but face challenges like differing legal-ethical frameworks across countries. This forces clinicians to rely on single-center expertise and institutional protocols, leading to inconsistent care. Pulmonary Embolism Response Teams (PERTs) are developing frameworks designed to facilitate a coordinated multidisciplinary approach to decision-making in PE cases [&lt;span&gt;14&lt;/span&gt;]. However, their national distribution is unbalanced. Addressing these inconsistencies on a national scale is essential to establish standardized approaches, gather robust data, and support the development of randomized clinical trials in this under-researched area.&lt;/p&gt;&lt;p&gt;To explore current practices and identify potential gaps in care, we conducted a national survey targeting clinicians involved in the management of PE in pregnancy across the UK and Ireland. The survey was distributed through the HaemSTAR network, a trainee-led organization that facilitates nationwide research and audits. HaemSTAR's decentralized network of regional representatives enabled targeted, and rapid data collection from diverse locations. The survey was administered electronically via Google Forms, following a process of informal validation through a two-stage feedback process. First, the survey pilot was distributed to the HaemSTAR committee for internal review, d","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716975","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 Confusing Case of Confusion: Bing–Neel Syndrome Treated With Zanubrutinib","authors":"Harrison Duell,&nbsp;Angela Clarke,&nbsp;Sally Bugg","doi":"10.1002/jha2.70114","DOIUrl":"https://doi.org/10.1002/jha2.70114","url":null,"abstract":"&lt;p&gt;An 83-year-old man was admitted with back pain, decline in mobility and fluctuating delirium. He had a past medical history of restless leg syndrome and pericarditis. Laboratory tests from admission showed haemoglobin concentration 112 g/L, neutrophils 2.5 ×10&lt;sup&gt;9&lt;/sup&gt;/L, lymphocytes 1.1 × 10&lt;sup&gt;9&lt;/sup&gt;/L, platelets 156 × 10&lt;sup&gt;9&lt;/sup&gt;/L, c-reactive protein 5 mg/L, adjusted calcium 2.33 mmol/L, creatinine 91 umol/L. Protein electrophoresis and immunofixation showed two paraprotein bands of 15.0 g/L and 16.9 g/L (IgG and IgM co-migration on immunofixation, with a total combined value of 31.9 g/L).&lt;/p&gt;&lt;p&gt;Serum light chains showed a free kappa of 1018.4 mg/L with kappa/lambda ratio of 98. Magnetic resonance imaging of the head with contrast and spine without contrast showed mild generalized atrophy within the cerebrum and no evidence of bony lesions. Computed tomography of the chest, abdomen and pelvis showed no evidence of lymph node enlargement.&lt;/p&gt;&lt;p&gt;Examination of the cerebrospinal fluid showed multiple mononuclear cells with the presence of plasmacytoid cells, consistent with infiltration (Figure 1). Flow cytometry was consistent with a clonal B-cell lymphoproliferative disorder:&lt;/p&gt;&lt;p&gt;Clonal B lymphocytes comprised 21% of total nucleated cells, immunophenotype showing CD19+, sIgKappa+, CD79b+, CD20+, CD5-, CD23-, CD10-, CD200-, CD43-.&lt;/p&gt;&lt;p&gt;Plasma cells comprised 4.5% of total nucleated cells, ∼18% had an abnormal immunophenotype showing CD38+, CD56+, CD27+, CD19+, CD45+.&lt;/p&gt;&lt;p&gt;Flow cytometry of the bone marrow aspirate showed:&lt;/p&gt;&lt;p&gt;Clonal B lymphocytes comprised 11% of total nucleated cells, immunophenotype showing CD19+, sIgKappa+, CD23+, CD79b+, CD38+, CD200+, CD20+, CD5-, CD10-, CD43-.&lt;/p&gt;&lt;p&gt;Plasma cells comprising 0.5% of total nucleated cells, abnormal immunophenotype showing CD38+, CD56+, CD27+, CD19+ and CD45+.&lt;/p&gt;&lt;p&gt;Within the bone marrow aspirate, MYD88 L265P was identified via droplet digital PCR at 5.1%. Trephine showed lymphoid aggregates within the interstitium, comprising lymphoid, lymphoplasmacytoid, and plasma cells (Figure 2). Trilineage haematopoiesis was well represented and Congo red staining did not demonstrate amyloid deposition. Reticulin staining slightly increased in association with the lymphoid aggregates. CD20 highlighted a predominant B cell population in the lymphoid aggregates as well as increased numbers of interstitial B-cells (Figure 3), accounting for 5% to 10% of overall cellularity. CD79a showed additional cells, accounting for 25% to 35% of overall cellularity. The B-cells showed kappa immunoglobulin light chain restriction and expression of IgM, with IgG highlighting very occasional plasma cells only. CD3 and CD5 staining showed mixed T-cells. There was no significant expression of CD56 or cyclin D1. CD138 highlighted plasma cells in an interstitial distribution as well as within some of the lymphoid aggregates, accounting for 5% of the cellularity of the sample. CD23 highlighted occasional cell","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705312","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":"Prompt Autologous Hematopoietic Stem Cell Transplant in Patients With Large B-Cell Lymphoma Is Associated With Lower Rates of Progression of Disease Prior to Transplant","authors":"Erin A. Dean,&nbsp;Rick Y. Lin,&nbsp;Tuo Lin,&nbsp;Derek M. Li,&nbsp;Jack W. Hsu,&nbsp;John W. Hiemenz,&nbsp;James W. Lynch Jr,&nbsp;John R. Wingard","doi":"10.1002/jha2.70108","DOIUrl":"https://doi.org/10.1002/jha2.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>To ensure response is preserved, it is common practice to continue chemotherapy in patients with large B-cell lymphoma (LBCL) awaiting autologous hematopoietic stem cell transplant (HSCT), even after they have achieved complete or partial response (CR/PR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective chart review of patients with LBCL evaluated at our institution between 2011 and 2022 to examine the effect of delay of transplant and continuation of chemotherapy past CR/PR on progression of disease (PD) prior to transplant. The association of PD prior to transplant with delayed transplant and additional chemotherapy was modeled using logistic regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of the 87 patients included, 74 (85%) had relapsed/refractory LBCL. Transplant was delayed in 20 (23%) patients, and 22 (25%) patients received chemotherapy after CR/PR. Delay of transplant was associated with higher odds of PD prior to transplant (odds ratio [OR] = 4.0, <i>p</i> = 0.034), as was additional chemotherapy use after CR/PR (OR = 2.2, <i>p</i> = 0.09).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Proceeding to autologous HSCT as soon as adequate response is achieved in LBLC was associated with a lower likelihood of progression of disease prior to transplant regardless of additional chemotherapy receipt.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The authors have confirmed that 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":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688183","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":"Multicenter Single-Blind Randomized Controlled Trial of the Romiplostim Biosimilar","authors":"Anait L. Melikyan,&nbsp;Ekaterina A. Protsenko,&nbsp;Galina N. Salogub,&nbsp;Bulat A. Bakirov,&nbsp;Igor L. Davydkin,&nbsp;Vladislav V. Kovalik,&nbsp;Mariia L. Gefen,&nbsp;Yuliia D. Matvienko,&nbsp;Valeria B. Saparova,&nbsp;Alexander L. Khokhlov,&nbsp;Igor E. Makarenko,&nbsp;Roman V. Drai","doi":"10.1002/jha2.70105","DOIUrl":"https://doi.org/10.1002/jha2.70105","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This was a randomized multicenter single-blinded active-controlled equivalence Phase III study evaluating the efficacy and safety of the biosimilar of romiplostim (GP40141) compared to the reference drug Nplate in patients with persistent or chronic immune thrombocytopenia (ITP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 136 adult patients randomized 1:1 to receive either the biosimilar or reference drug for 26 weeks. The primary endpoint was the proportion of patients achieving a platelet response (≥ 50 × 10⁹/L) at Week 11. Key secondary endpoints included proportion of patients with durable platelet response, stable response in treatment-naive patients, incidence of bleeding, and rescue therapy usage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The proportion of patients with platelet response after 10 weeks of therapy was 78% in the test group and 85% in the comparison group. The absolute difference in proportion between groups was −0.06 (95% CI [−0.196, 0.068] and it falls within the equivalence limits [−0.225, 0.225]). The study demonstrated equivalence in the primary endpoint, with no significant differences between the biosimilar and reference drug groups in durable responses rate, bleeding events, or safety profiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results support the biosimilar romiplostim as an equivalent and comparable treatment option to the reference drug for patients with persistent or chronic ITP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>NCT06497036</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688047","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":"Safety, Efficacy, and Patient-Reported Outcomes From a Phase 2 Randomized Trial of Pozelimab and Cemdisiran Combination in Patients With Paroxysmal Nocturnal Hemoglobinuria","authors":"Jun-Ho Jang,&nbsp;Raymond Siu Ming Wong,&nbsp;Christopher Hartford,&nbsp;Rodrigo Pavani,&nbsp;Lisa Aurand,&nbsp;Quang Nguyen,&nbsp;Kosalai Mohan,&nbsp;Karoline Meagher,&nbsp;Steven Sherman,&nbsp;Diana Rofail,&nbsp;Lorah Perlee,&nbsp;Amal Souttou,&nbsp;Richard J. Kelly","doi":"10.1002/jha2.70095","DOIUrl":"https://doi.org/10.1002/jha2.70095","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, life-threatening disease associated with chronic intravascular hemolysis due to uncontrolled complement activation. PNH results in anemia with an increased risk of thrombosis, and often causes severe fatigue, and decreased physical function and health-related quality of life (QoL). We investigated the efficacy, safety, and patient-reported outcomes data of the combination of pozelimab (a fully human monoclonal antibody) and cemdisiran (an <i>N</i>-acetylgalactosamine-conjugated small interfering ribonucleic acid) from a Phase 2 trial (NCT04811716) in patients with PNH who transitioned from pozelimab monotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this randomized, open-label, Phase 2 study, patients were randomized (1:1) to one of two treatment arms; both arms received subcutaneous cemdisiran 200 mg every 4 weeks (Q4W) plus subcutaneous pozelimab 400 mg either Q4W (Arm 1) or every 2 weeks (Arm 2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-four patients were treated with combination dosing. During the 28-week open-label treatment period (OLTP), 20 patients (83.3%) maintained control of lactate dehydrogenase (≤ 1.5 × upper limit of normal) at all timepoints. The majority of patients (92%) did not require a blood transfusion. While most patients (66.7%) experienced treatment-emergent adverse events, the majority of these events were mild to moderate in severity. No meningococcal infections, thrombotic events, or deaths were reported. The combination therapy maintained improvements in patient-reported fatigue, physical functioning, and QoL throughout the OLTP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Combination treatment maintained adequate hemolysis control and was generally well tolerated. Administration of pozelimab Q2W did not improve disease control as compared to pozelimab Q4W.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov/NCT04811716</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688046","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}