Acta Haematologica最新文献

{"title":"Prelims.","authors":"","doi":"10.1159/000550475","DOIUrl":"https://doi.org/10.1159/000550475","url":null,"abstract":"","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":"149 1","pages":"1-4"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Cellular Therapies: The Expanding Role of Antibody-Driven Immunotherapy in Pediatric Acute Lymphoblastic Leukemia.","authors":"David McCall, Samanta Catueno, Ramya Ramakrishnan, Priti Tewari, Irtiza Sheikh, Amber Gibson, Cesar A Nuñez, Miriam B Garcia, Branko Cuglievan","doi":"10.1159/000546249","DOIUrl":"10.1159/000546249","url":null,"abstract":"<p><strong>Background: </strong>The integration of novel antibody-mediated targeted therapies into both relapsed/refractory (R/R) and frontline pediatric acute lymphoblastic leukemia (ALL) treatment protocols has led to critical advancements in the field. Current research efforts focus on optimizing targeted therapies to enhance precision and efficacy while minimizing toxicity by reducing chemotherapy. A notable example is the addition of blinatumomab, demonstrating superiority over conventional chemotherapy, with an 8% increase in disease-free survival at an interim analysis, reaching 96%. Inotuzumab ozogamicin (InO) has also shown promise, achieving nearly a 70% complete response rate in pediatric R/R B-cell ALL (B-ALL) trials. Additionally, daratumumab in T-cell ALL (T-ALL) and chimeric antigen receptor T-cell therapies, particularly CD19-directed (B-ALL) and CD7-directed (T-ALL) strategies, are under active investigation.</p><p><strong>Summary: </strong>This review will provide an overview of targeted antibody-mediated immunotherapies in both B-ALL and T-ALL, with a focus on their pediatric applications, supporting data, and future prospects.</p><p><strong>Key messages: </strong>The next cycle of frontline trials in pediatric ALL will incorporate more immunotherapy with reduction of chemotherapy. Subsequent trials will utilize more concurrent chemoimmunotherapy blocks as precision testing and risk-adapted therapy will continue to develop. These advancements reflect a paradigm shift toward more precise, less toxic treatment strategies in pediatric ALL.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"84-100"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Causal Relationship between Lipid Metabolites and Multiple Myeloma Risk: A Mendelian Randomization Study.","authors":"Jian Tao, Ling Wang, Zheyun Gu","doi":"10.1159/000548566","DOIUrl":"10.1159/000548566","url":null,"abstract":"<p><strong>Introduction: </strong>Research has demonstrated a potential link between lipid metabolites and multiple myeloma (MM); however, the causal relationship remains uncertain. This Mendelian randomization (MR) study aimed to explore the potential causal relationship between lipid metabolites and MM.</p><p><strong>Methods: </strong>In this study, data on lipid metabolites were obtained from a genome-wide association study of metabolites in blood samples from 7,824 Europeans. Genetic information related to MM came from the UK Biobank database, encompassing 601 patients with MM and 372,016 control samples. In this MR analysis, inverse-variance weighted method was used as the primary analysis method; MR-Egger and weighted median were employed as complementary approaches. Sensitivity analyses were conducted using the Cochran Q test, MR-Egger intercept, MR-PRESSO, and leave-one-out analysis.</p><p><strong>Results: </strong>A total of 121 human lipid metabolites were analyzed in this MR study. The analysis result revealed that 1-docosahexaenoyl-glycerophosphocholine (odds ratio [OR] = 1.0059, 95% confidence interval [CI] 1.0043-1.0076, p < 0.01, FDR = 0.12), tetradecanedioate (OR = 1.0007, 95% CI: 1-1.0013, p = 0.0498, FDR = 0.23), and X-12990-docosapentaenoic acid (OR = 1.0029, 95% CI: 1.0015-1.0044, p < 0.01, FDR = 0.15) were linked to an increased risk of MM. As for palmitoleate (OR = 0.9972, 95% CI: 0.9947-0.9997, p = 0.0299, FDR = 0.19), a nominal inverse association was observed. None of these associations reached statistical significance after FDR correction (all FDR >0.05). Sensitivity analyses verified the robustness of these nominally significant results.</p><p><strong>Conclusion: </strong>Genetic evidence demonstrated nominal associations of 1-docosahexaenoyl-sn-glycero-3-phosphocholine, tetradecanedioate, X-12990-eicosapentaenoic acid, and palmitoleate with MM risk, though these did not survive FDR correction. While these findings suggest potential metabolic pathways in MM pathogenesis, further validation is required before considering these compounds as biomarkers for clinical screening or drug target selection.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"396-412"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ring Chromosomes in Patients with Myeloid Neoplasms Are Associated with a Poor Response to Therapy.","authors":"Daniel I Nathan, Ronald Hoffman, Daiva Ahire, John Mascarenhas, Bridget K Marcellino, Douglas Tremblay, Lewis R Silverman, Vesna Najfeld, Jonathan Feld","doi":"10.1159/000546757","DOIUrl":"10.1159/000546757","url":null,"abstract":"<p><p><p>Introduction: Ring chromosomes (RCs) are acquired circular structural abnormalities associated with gain or loss of genetic material, which are thought to be associated with inferior outcomes in patients with myeloid neoplasms (MNs). Responses of patients with MN and RC to the standard therapeutic options have not been previously reported.</p><p><strong>Methods: </strong>We analyzed the demographics and outcomes of 31 consecutive patients with an MN and RC, comparing overall survival (OS) and progression-free survival (PFS) of patients who received supportive care (n = 9), cytotoxic chemotherapeutic options (n = 3), hypomethylating agents (HMA) alone (n = 6), or HMA in combination with venetoclax (n = 13).</p><p><strong>Results: </strong>Over 60% of all patients with RC had either a TP53 mutation, loss of 17p, or both. Interestingly, 22/31 (71%) of patients had not received prior radiation or chemotherapy. Patients who received supportive care had a shorter OS (p = 0.001), but none of the therapeutic interventions were associated with further improvement in prolonging OS (p = 0.86) or PFS. The presence of a complex karyotype, TP53 mutations/loss of TP53, or a treatment-related MN was not independently associated with an inferior OS in MN patients with RCs.</p><p><strong>Conclusion: </strong>These findings indicate that patients with MN and RC have especially poor outcomes and that effective treatment strategies remain an unmet need. </p>.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"287-296"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Insights into Avatrombopag's Effectiveness and Safety in Adults with Primary Immune Thrombocytopenia: A Retrospective Analysis from Central and Eastern Europe.","authors":"Barbara Skopec, Dražen Pulanić, Libor Červinek","doi":"10.1159/000547576","DOIUrl":"10.1159/000547576","url":null,"abstract":"<p><strong>Introduction: </strong>Primary immune thrombocytopenia (ITP) is an autoimmune condition marked by low platelet counts, leading to symptoms such as bleeding. Avatrombopag (AVA), a second-generation thrombopoietin receptor agonist, has shown efficacy in clinical trials but lacks extensive real-world data, particularly in Central and Eastern Europe (CEE). This study aims to evaluate the effectiveness and safety of AVA in routine clinical practice for ITP patients across CEE countries.</p><p><strong>Methods: </strong>A multicenter, noninterventional, retrospective analysis was conducted in Slovenia, Croatia, and the Czech Republic, involving 41 patients treated with AVA for primary ITP. The primary endpoint was achieving a platelet response at week 8 (W8).</p><p><strong>Results: </strong>AVA treatment resulted in a 68.3% platelet response rate by W8, with a significant increase in median platelet counts. Rescue medication use decreased post-AVA initiation, and many patients reduced or discontinued steroids. AVA was well-tolerated, with only one adverse event reported and no significant bleeding events.</p><p><strong>Conclusion: </strong>AVA is effective in improving platelet counts and reducing medication dependency in ITP patients in CEE countries. It offers a viable treatment option with a favorable safety profile, supporting its use across different ITP stages and patient demographics.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"433-443"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-Transplant Lymphoproliferative Disorder following Heart Transplantation Presenting as a Retroperitoneal Plasmacytoma: A Case Report and Review of the Literature.","authors":"Yair Vilian, Adi Sherban, Elad Goldberg, Tal Wax, Eytan Cohen, Nofar Hezkelo, Liron Sheena, Iuliana Vaxman, Pia Raanani, Ilan Krause, Idan Goldberg","doi":"10.1159/000550220","DOIUrl":"10.1159/000550220","url":null,"abstract":"<p><p><p>Introduction: Plasma cell neoplasms (PCNs) are a rare type of post-transplant lymphoproliferative disease (PTLD). Extramedullary plasmacytoma is a rare type of PCN, and is infrequently located in the retroperitoneum. According to the current literature, heart transplant recipients are considered at intermediate risk for developing PTLD. Case Presentation: We report a case of a 70-year-old patient with a history of heart transplantation, who was admitted to the hospital with back pain and swelling of the left lower limb. Imaging revealed a large retroperitoneal mass involving the left kidney, descending colon, left iliopsoas muscle, bladder, and prostate. Histopathological analysis confirmed the diagnosis of extramedullary plasmacytoma. Immunosuppressive therapy was reduced and chemotherapy was initiated; however, the patient passed away after two cycles of treatment. Conclusion: To the best of our knowledge, only once has retroperitoneal plasmacytoma in a heart transplant recipient been previously reported. Our case should raise suspicion for recognizing and considering this rare diagnosis in similar clinical scenarios. </p>.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"613-620"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12858189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of B- and T-Cell Receptor Repertoires Reveals Distinct Mechanisms in Pure Red Cell Aplasia, Autoimmune Hemolytic Anemia, and Aplastic Anemia.","authors":"Ruoxi Zhang, Bing Han","doi":"10.1159/000547027","DOIUrl":"10.1159/000547027","url":null,"abstract":"<p><p><p>Introduction: Pure red cell aplasia (PRCA), autoimmune hemolytic anemia (AIHA), and aplastic anemia (AA) are immune-mediated diseases that affect mainly erythrocytes or erythroid progenitor cells. This study aimed to investigate changes related to autoimmunity in B-cell receptor (BCR) and T-cell receptor (TCR) repertoires in patients with these diseases.</p><p><strong>Methods: </strong>Patients with primary PRCA, AIHA, and AA and normal controls (NCs) were recruited. Peripheral blood was collected, and BCR and TCR repertoires were sequenced by next-generation immunosequencing.</p><p><strong>Results: </strong>Ten patients with PRCA, 10 with AIHA, 10 with AA, and 7 NCs were ultimately enrolled. According to the broad repertoire metric analysis, only the TCR repertoire of the AA group was more diverse than that of the NC group (p < 0.05). Regarding BCR and TCR repertoires, the PRCA, AIHA, and AA groups had uniform gene characteristics. The preferential gene of immunoglobulin heavy chains in PRCA patients was correlated with memory cell and red blood cell antigen recognition; genes expressed in the AIHA group were associated with the secretion of autoantibodies, whereas AA patients had more genes related to neutralizing antibodies. For T-cell receptor β (TRB) chains, PRCA patients had skewed use of genes associated with T-cell dysregulation and hyperinflammation, whereas AIHA and AA patients had similar genes as patients with other autoimmune diseases, which correlated with abnormal antigen recognition. PRCA and AA patients had specific TRBV-J gene combinations. For the BCR light chains, PRCA and AIHA patients tended to use more κ chains, whereas AA patients tended to use more λ chains. Regarding the TCRα chains, patients with each of the three diseases expressed more genes related to hypersensitivity reactions (p < 0.05). Compared to the NC group, the PRCA and AIHA groups had greater BCR somatic hypermutation (SHM). The length of CDR3 was similar, but the hydrophobicity differed among the different disease groups. Different motifs were found in BCRs and TCRs of the three diseases. Compared to NCs, the PRCA, AIHA, and AA groups showed a considerable lack of physiological T-cell clusters, and some disease-specific T-cell clusters were found in each disease group.</p><p><strong>Conclusion: </strong>PRCA, AIHA, and AA patients had different BCR and TCR repertoire characteristics in terms of genes and gene combinations, hydrophobicity and CDR3 motifs, and T-cell clustering, which might contribute to autoimmune antigen recognition. The abnormalities were mainly T-cell related for PRCA patients, B-cell related for AIHA patients and both for AA patients. </p>.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"263-279"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond CAR-T: The Rise of CAR-NK/T Cells for Haematological Cancer.","authors":"Mohammadamin Noorafrooz, Robert Peter Gale, Mohadese Dashtkoohi","doi":"10.1159/000547531","DOIUrl":"10.1159/000547531","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor (CAR)-natural killer (NK)/T-cells offer a new approach in immune therapy of haematological cancers. NK/T-cells bridge innate and adaptive immunity with strong anti-cancer effects. Unlike allogeneic CAR-T-cells, CAR-NK/T-cells do not require TCR genetic deletion to prevent major MHC recognition, have a lower risk of graft-versus-host disease, and can be used universally.</p><p><strong>Summary: </strong>Pre-clinical studies report CAR-NK/T-cells effectively target antigens such as CD19 and B-cell maturation antigen in B-cell lymphomas and plasma cell myeloma. Compared with CAR-T-cells, CAR-NK/T-cells have faster immune responses, more cytotoxicity and better safety. Recent innovations increase efficacy of CAR-NK/T-cell therapies. Early clinical trials report promising safety and efficacy. Although still in the early phases of development, advances in NK/T-cell therapy are overcoming prior challenges.</p><p><strong>Key messages: </strong>CAR-NK/T-cells may prove a safer, more flexible form of cell therapy of haematological cancers.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"313-327"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Philadelphia-Positive Acute Lymphoblastic Leukemia.","authors":"Anna Torrent, Josep Maria Ribera","doi":"10.1159/000547026","DOIUrl":"10.1159/000547026","url":null,"abstract":"<p><strong>Background: </strong>Philadelphia chromosome-positive acute lymphoblastic leukemia has historically been associated with poor prognosis and limited therapeutic options. Over the past 2 decades, however, the treatment paradigm has markedly shifted.</p><p><strong>Summary: </strong>The introduction of tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, and ponatinib, has revolutionized frontline therapy, significantly improving remission rates and long-term survival. These agents, when combined with reduced-intensity chemotherapy or even with corticosteroids, have enabled less toxic regimens, particularly beneficial for older or unfit patients. The implementation of measurable residual disease monitoring has emerged as a pivotal tool for risk stratification and therapeutic decision-making. Consequently, the role of allogeneic hematopoietic stem cell transplantation, considered a cornerstone of curative treatment, is being reevaluated in patients achieving sustained deep molecular responses. More recently, immunotherapeutic strategies - including the bispecific T-cell engager blinatumomab and chimeric antigen receptor (CAR) T-cell therapies - have emerged as effective alternatives to conventional chemotherapy and TKIs.</p><p><strong>Key messages: </strong>While TKIs remain the backbone of treatment, the integration of immunotherapeutic strategies - including bispecific antibodies and CAR T-cell therapy - has expanded therapeutic options, not only in the R/R setting but increasingly in frontline regimens. Ongoing research aimed at optimizing the sequencing, combination, and duration of these therapies is essential to further enhance clinical outcomes.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"24-38"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Subclassification and Risk Stratification of ALL.","authors":"Anna Østergaard, Ilaria Iacobucci","doi":"10.1159/000547135","DOIUrl":"10.1159/000547135","url":null,"abstract":"<p><strong>Background: </strong>Over the last 2 decades, significant improvements have been made in the understanding of the genomic and biological bases of acute lymphoblastic leukemia (ALL), resulting in enhanced genomic classification, more precise risk stratification, and improved long-term outcomes. ALL is a hematologic malignancy defined by uncontrolled proliferation of immature B- or T-lymphoid blasts in the bone marrow, blood, and other extramedullary tissues. It affects most commonly children, representing the most common childhood cancer, but it also occurs in adults where outcome tends to be poorer compared to pediatric patients.</p><p><strong>Summary: </strong>A variety of genetic aberrations, including structural and numerical chromosome alterations, translocations generating fusion oncoproteins, cryptic genomic rearrangements, sequence mutations, and genomic copy number changes, define multiple genomic subtypes, influence risk stratification and determine response to therapeutic strategies.</p><p><strong>Key messages: </strong>In this review, we describe the updated genomic classification of ALL highlighting new biological insights and discussing their implications for prognostication and outcome.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"8-23"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}