{"title":"Comparative Analysis of 12 Flow Cytometry-Based Markers in B-Lymphoblastic Leukemia/Lymphoma and Their Utility in Detecting Minimal/Measurable Residual Disease.","authors":"Tharageswari Srinivasan, Nabhajit Mallik, Parveen Bose, Arun Kumar, Bhavishan Lal, Kajol Jawallia, Praveen Sharma, Sreejesh Sreedharanunni, Man Updesh Singh Sachdeva, Reena Das, Alka Khadwal, Pankaj Malhotra, Amita Tehran","doi":"10.1111/ijlh.70053","DOIUrl":"10.1111/ijlh.70053","url":null,"abstract":"<p><strong>Introduction: </strong>Minimal/measurable residual disease (MRD) is a key prognostic factor in B-lymphoblastic leukemia/lymphoma (B-ALL/LBL), commonly assessed via multiparametric flow cytometry (MFC). This study evaluated 12 leukemia-associated immunophenotype (LAIP) markers-CD81, CD86, CD123, CD58, CD9, CD73, CD13/CD33, CD44, CD97, CD66c, CD49f, and CD304-to determine their suitability for MRD detection.</p><p><strong>Methods: </strong>Marker expression was analyzed in 103 B-ALL cases at diagnosis, and 54 post-therapy follow-up samples, including 16 MRD-positive cases. Additionally, 25 non-B-ALL bone marrow samples were examined for marker expression in hematogones. Clinical and genetic correlation was also performed.</p><p><strong>Results: </strong>Median age of patients was 9 years (range: 0.3-89), with male: female ratio of 1:1. We found that CD97, CD73, CD86, and CD58 are excellent markers for MRD analysis in B-ALL, as they are expressed in more than 85% of cases at baseline, and their expression is preserved in more than 75% of cases post-therapy. Two other extremely promising markers are CD81 and CD49f, both of which are expressed as LAIP in more than 50% of B-ALL cases, with retention of expression in more than 85% of cases post-therapy, and importantly, expression as LAIP in some post-therapy samples despite their absence at baseline. Hyperdiploidy was significantly associated with expression of CD86, CD97, CD123, CD66c, and CD9; BCR::ABL1 fusion was associated with CD49f, CD81, and CD66c.</p><p><strong>Conclusion: </strong>CD97, CD73, CD86, and CD58 are the best amongst newer markers in B-ALL MRD assessment. Our findings support integrating these into MRD panels to enhance post-therapy MRD detection, thus improving prognostication and guiding treatment decisions.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"589-597"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ching Li, Yi-Hua Wang, Shwu-Ing Meng, Shih-Chieh Chen, Jia-Arng Lee
{"title":"Discrepancy Between White Blood Cell Count Channels as a Clue to Malaria Infection.","authors":"Ching Li, Yi-Hua Wang, Shwu-Ing Meng, Shih-Chieh Chen, Jia-Arng Lee","doi":"10.1111/ijlh.70067","DOIUrl":"10.1111/ijlh.70067","url":null,"abstract":"","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"490-492"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nikolaos Androulakis, Olga Striligka, Eleni Nioti, Antonios Dilintas, Aikaterini Darivianaki, Anastasia Papadopoulou, Fotini Nistikaki, Theodosia Iatridi, Marilena Kampa, Christina Kalpadakis
{"title":"Lupus Anticoagulant and Complement C4 Consumption in Antiphospholipid Antibody Testing: Disentangling Inflammation From Autoimmunity.","authors":"Nikolaos Androulakis, Olga Striligka, Eleni Nioti, Antonios Dilintas, Aikaterini Darivianaki, Anastasia Papadopoulou, Fotini Nistikaki, Theodosia Iatridi, Marilena Kampa, Christina Kalpadakis","doi":"10.1111/ijlh.70075","DOIUrl":"10.1111/ijlh.70075","url":null,"abstract":"<p><strong>Introduction: </strong>Antiphospholipid antibodies (aPL) define the laboratory criteria for antiphospholipid syndrome (APS), but their relationships with complement consumption, inflammation, and modifiers such as sex remain uncertain. Our central hypothesis was that C4 consumption represents a more specific indicator of immune-complex-driven autoimmunity than composite complement definitions or CRP, which more often reflect nonspecific inflammatory activation.</p><p><strong>Methods: </strong>We retrospectively analyzed 1260 patients tested for lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2-glycoprotein I (anti-β2GPI), with complement (C3, C4) and C-reactive protein (CRP) available in subsets. This retrospective, fully anonymized laboratory study was approved by the Institutional Review Board. Patients were grouped into eight serological phenotypes. Multivariable logistic regression examined associations with low complement, low C4, and CRP > 1.0 mg/dL, adjusting for sex and inpatient status. Principal component analysis (PCA) identified four components explaining ~86% of variance; clustering was exploratory.</p><p><strong>Results: </strong>Low C4 was most strongly associated with LA + aCL and triple-positive profiles and showed good discrimination (AUC 0.84), whereas composite definitions of low complement were less informative (AUC 0.73). Anti-β2GPI-only positivity was linked only to the composite low complement outcome. Low complement occurred more frequently in women. CRP elevation was mainly associated with inpatient status (aOR = 3) and was more common in men, with weaker associations observed for LA-only and multi-positive profiles. The CRP model showed only fair discrimination (AUC 0.68).</p><p><strong>Conclusions: </strong>C4 showed the strongest association in this dataset, whereas CRP largely reflected nonspecific inflammation, especially in hospitalized men. Observed sex-associated patterns were present, with women more often showing complement consumption and men more often showing CRP elevations. These findings indicate that C4 showed a clearer analytical signal than composite definitions, while CRP should be interpreted cautiously. Prospective studies with linked clinical outcomes are needed for validation.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"636-645"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ünsal Özgen, Filiz Orhon, Gonca Keskindemirci, Bahar Çuhacı Çakır, Meda Kondolot, Habip Almış, Yaşar Topal, Kamil Yılmaz, Perran Boran, Emel Gür, Mehmet Ali Cengiz, Seda Topçu, Aysu Duyan Çamurdan, Hatice Topal, Tuğba Ayçiçek Dinçer, Gülbin Gökçay, Mahsum Aslan, Filiz Tubaş, Ezgi Barış, Özge Kaynar
{"title":"Pediatric Reference Intervals for Complete Blood Count Parameters in Healthy Turkish Infants and Children.","authors":"Ünsal Özgen, Filiz Orhon, Gonca Keskindemirci, Bahar Çuhacı Çakır, Meda Kondolot, Habip Almış, Yaşar Topal, Kamil Yılmaz, Perran Boran, Emel Gür, Mehmet Ali Cengiz, Seda Topçu, Aysu Duyan Çamurdan, Hatice Topal, Tuğba Ayçiçek Dinçer, Gülbin Gökçay, Mahsum Aslan, Filiz Tubaş, Ezgi Barış, Özge Kaynar","doi":"10.1111/ijlh.70068","DOIUrl":"10.1111/ijlh.70068","url":null,"abstract":"<p><strong>Purpose: </strong>The study aims to provide reference ranges of complete blood count (CBC) parameters in healthy children in Türkiye.</p><p><strong>Methods: </strong>Children aged 1 month to -18 years who were administered to the Well Child Outpatients Clinics of Department/Unit of Social Pediatrics in 10 centers in different regions of Türkiye were included in the study. Complete blood count measurements were collected from these centers.</p><p><strong>Results: </strong>A total of 24 115 healthy infants and children (12 204 males and 11 911 females) aged 1 month-18 years old were enrolled. Mean and median values of the red blood cell, white blood cell, and platelet parameters according to the age groups are presented in this study. In addition, the nonparametrically determined CBC reference intervals (RIs) corresponding to the 2.5th to 97.5th percentile, stratified by age and sex were provided.</p><p><strong>Conclusion: </strong>This is the first study that established RIs for hematological parameters in Turkish children younger than 18 years old. These data provide a more reliable basis for hematological evaluation across all pediatric healthcare disciplines in Türkiye.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"581-588"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hematopathology Practice in the Digital Era: What has Changed?","authors":"Olga Pozdnyakova","doi":"10.1111/ijlh.14515","DOIUrl":"10.1111/ijlh.14515","url":null,"abstract":"<p><p>Hematopathology workflows are complex, since they include numerous data points necessary for guiding further testing, diagnosis, and patient management. The workflows start with complete blood cell counts, with subsequent morphologic evaluation of peripheral blood (PB) and bone marrow (BM). Digital pathology has the potential to revolutionize PB and BM assessment through the implementation of artificial intelligence for assisted and automated evaluation, but there remain major hurdles toward this ultimate goal, such as lack of regulatory oversight, data standardization, insufficient knowledge and training, and resistance to change, among others. This article reviews the current state of digitalization in the hematopathology practice, recent research using machine learning models for automated specimen analysis, outlines the advantages and barriers facing clinical implementation of artificial intelligence, and offers prospective artificial intelligence-driven clinical workflows for efficient and comprehensive clinical workup.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"503-511"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850181","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":"Significance of Myelodysplasia-Related Mutations and the Genetic Landscape of Acute Leukemias of Ambiguous Lineage.","authors":"Timothy J Kirtek, Olga K Weinberg","doi":"10.1111/ijlh.14529","DOIUrl":"10.1111/ijlh.14529","url":null,"abstract":"<p><p>The recent fifth edition WHO classification and ICC classification systems have moved further toward genetically defined classifications of acute leukemias. Both now recognize myelodysplasia-related (MR) mutations as defining of MDS-related AML (AML-MR). Acute leukemias of ambiguous lineage (ALAL) are a heterogenous group of acute leukemias characterized by leukemic blasts that either express markers of multiple lineages, mixed phenotype acute leukemia (MPAL), or too few to be assigned a definitive lineage, acute undifferentiated leukemia (AUL). However, the recent classifications are unclear on how ALALs should be categorized in the presence of MR mutations. In short, the current recommendations are to classify cases that are immunophenotypically consistent with ALAL but harbor MR cytogenetics or mutations as AML-MR. Due to their rarity, investigations into the genetic basis of ALAL are limited but show great heterogeneity in their mutational landscapes. Data on the frequencies and significance of MR mutations in ALAL is particularly scant. Our comprehensive review of the literature reporting on the genetic landscapes of MPAL and AUL shows that a significant proportion of MPAL and AUL cases, ~32% and ~59% on average respectively, may harbor one or more mutations in MR genes, with mutations in RUNX1 and ASXL1 among the most common. Additional research is needed into the clinical, immunophenotypic, and genetic characteristics of ALAL to aid in refining classification and to support therapeutic decision making.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"512-520"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602639","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}
Richard K Wood, Ibrahim Elsharawi, Marissa Goudie, Helene Bruyère, Mahboubeh Rahmani, Tanya L Gillan
{"title":"The ABCs of IGHV Testing in Chronic Lymphocytic Leukaemia: Current Recommendations, Ongoing Challenges, and Future Directions.","authors":"Richard K Wood, Ibrahim Elsharawi, Marissa Goudie, Helene Bruyère, Mahboubeh Rahmani, Tanya L Gillan","doi":"10.1111/ijlh.70010","DOIUrl":"10.1111/ijlh.70010","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) is the most common low-grade B-cell neoplasm worldwide. While diagnostic criteria are well established, prognostication and management of this disease are an evolving field, owing to the biological and clinical heterogeneity of CLL. Molecular, cytogenetic, and immunogenetic workup are key in the management of CLL, and include evaluation for specific gene variants, copy number variants (CNVs), and detailed analysis of the immunoglobulin heavy chain variable region (IGHV) with respect to somatic hypermutation (SHM) status and the presence of recurrent stereotyped IGHV subsets. IGHV status has significant prognostic, predictive, and therapeutic implications in CLL and has been incorporated into multiple risk stratification systems. The advent of both next-generation sequencing (NGS) and novel targeted therapies has added further complexity to immunogenetic analysis in CLL. Owing to the necessity and growing complexity of IGHV analysis, the European Research Initiative on CLL (ERIC) developed guidelines to standardize methods for immunogenetic analysis and provide recommendations for interpretation of challenging cases (including multiple productive IGHV clones and discordant SHM status) and has published multiple updates, revising recommendations and raising new questions. This review discusses the biology and clinical significance of IGHV status in CLL as well as laboratory methodology in immunogenetic analysis, the evolution of the ERIC recommendations leading into the era of NGS, and recent advances and emerging strategies in this field.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"541-550"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinicopathological and Immunophenotypic Analysis of Early T-Cell Precursor Acute Lymphoblastic Leukemia With Application of the Tokyo Children's Cancer Study Group Flow Cytometry Scoring System.","authors":"Soundarya Ravi, Narasimhapriyan Kannan, Prabhu Manivannan, Rakhee Kar, Smita Kayal","doi":"10.1111/ijlh.70065","DOIUrl":"10.1111/ijlh.70065","url":null,"abstract":"<p><strong>Introduction: </strong>Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL defined by an immature immunophenotype and unique molecular features. It is often associated with chemoresistance and poor outcomes. Accurate recognition is crucial for therapy optimization and consideration of hematopoietic stem cell transplantation. This study evaluated the Tokyo Children's Cancer Study Group (TCCSG) six-marker flow cytometric scoring system in identifying ETP-ALL and assessed its clinicopathological features and treatment outcomes.</p><p><strong>Methods: </strong>All consecutive T-ALL cases diagnosed between 2019 and 2023 were retrospectively analyzed. Clinical, immunophenotypic, and treatment-related data were compared between ETP-ALL and non-ETP-ALL subgroups. The TCCSG six-marker scoring system (CD34, HLA-DR, CD8, CD5, CD13, CD33) was applied, and receiver operating characteristic curve analysis determined the optimal cutoff for diagnosis.</p><p><strong>Results: </strong>Among 104 T-ALL cases, 25 (24.1%) were classified as ETP-ALL. ETP-ALL was more common in adults (> 18 years; 72.0% vs. 48.1%; p = 0.037). Compared with non-ETP-ALL, patients showed lower leukocyte counts (< 100 × 10<sup>9</sup>/L), fewer peripheral blasts, and higher platelet counts (p < 0.05). At end-of-induction (EOI), complete remission rates were lower in ETP-ALL (73.3% vs. 96.6%; p = 0.014), though no significant differences were observed in EOI measurable residual disease, consolidation response, or survival between the groups. A cutoff score ≥ 3 using the TCCSG system yielded 88% sensitivity and 94.9% specificity (AUC = 0.986; p = 0.0001).</p><p><strong>Conclusion: </strong>ETP-ALL represents a biologically distinct T-ALL subtype with inferior early treatment responses. The TCCSG six-marker scoring system is reliable, accurate, and practical for routine diagnosis, particularly in resource-limited settings.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"607-614"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diagnosing Systemic Mastocytosis: State of the Art.","authors":"Anton Rets, Tracy I George","doi":"10.1111/ijlh.70011","DOIUrl":"10.1111/ijlh.70011","url":null,"abstract":"<p><p>With the advent of effective multikinase and selective tyrosine kinase inhibitors in systemic mastocytosis, diagnosing this rare disease has been critical to improving patient morbidity and mortality. This state-of-the-art review interprets the international diagnostic criteria, including differences between the WHO 5th edition classification and the International Consensus Classification. Subclassification of systemic mastocytosis is critical for correct therapeutic strategies, and diagnostic difficulties are described for the practicing pathologist. Morphologic mimics, which require alternative treatment, are discussed.</p>","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"551-560"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245978","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 Blood Neutrophil Maturation as a Practical Predictor of Treatment-Free Remission in CML.","authors":"Mai Fujita, Hiroshi Ureshino, Shinya Kimura","doi":"10.1111/ijlh.70062","DOIUrl":"10.1111/ijlh.70062","url":null,"abstract":"","PeriodicalId":94050,"journal":{"name":"International journal of laboratory hematology","volume":" ","pages":"664-667"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}