Valentina Sangiorgio, Federica Mottadelli, Fabio Pagni, Fabrizio Cavalca, Giovanni Cazzaniga, Martina Venegoni, Carlo Gambacorti-Passerini, Rocco Piazza, Elena Maria Elli
Introduction
The majority of patients with essential thrombocythemia (ET) show somatic mutations of JAK2, CALR, or MPL. Around 10% of cases lack these mutations (“triple negative” ET, TN-ET). Additionally, some patients with bona fide “primary thrombocytosis” (PT) [i.e., high platelet (PLT)- count with no apparent underlying causes] do not fulfill the histologic criteria of ET. In this context, Next Generation Sequencing (NGS) can provide evidence of clonality and identify patients with different clinical behaviors.
Methods
We conducted a retro-prospective analysis of 39 patients with TN-PT and correlated the clinical and pathologic features with the molecular findings.
Results
Bone marrow histopathological features were consistent with ET in 60% of cases. After a mean follow up of 11.1 years, no cases of secondary myelofibrosis nor acute leukemia were observed. We reported 15 thrombotic events (TEs) in 10 (25.6%) patients. Considering mutations with a variant frequency ≥ 5%, 15.4% of patients showed at least one mutation (“NGS-positive”); the remaining had no mutations (“NGS-negative”). NGS status predicted the incidence of TEs: NGS-positive patients experienced a significantly higher rate of TEs compared to NGS-negative patients (66.6% vs. 18.2%, respectively; p = 0.01).
Conclusion
NGS status represents an adjunctive risk factor for thrombosis in TN-PT and provides useful clinical information.
{"title":"Next Generation Sequencing Identifies Subgroups of Patients With Triple Negative Primary Thrombocytosis With Different Clinical Thrombotic Outcomes","authors":"Valentina Sangiorgio, Federica Mottadelli, Fabio Pagni, Fabrizio Cavalca, Giovanni Cazzaniga, Martina Venegoni, Carlo Gambacorti-Passerini, Rocco Piazza, Elena Maria Elli","doi":"10.1111/ijlh.14476","DOIUrl":"10.1111/ijlh.14476","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The majority of patients with essential thrombocythemia (ET) show somatic mutations of <i>JAK2, CALR</i>, or <i>MPL</i>. Around 10% of cases lack these mutations (“triple negative” ET, TN-ET). Additionally, some patients with <i>bona fide</i> “primary thrombocytosis” (PT) [i.e., high platelet (PLT)- count with no apparent underlying causes] do not fulfill the histologic criteria of ET. In this context, Next Generation Sequencing (NGS) can provide evidence of clonality and identify patients with different clinical behaviors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retro-prospective analysis of 39 patients with TN-PT and correlated the clinical and pathologic features with the molecular findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Bone marrow histopathological features were consistent with ET in 60% of cases. After a mean follow up of 11.1 years, no cases of secondary myelofibrosis nor acute leukemia were observed. We reported 15 thrombotic events (TEs) in 10 (25.6%) patients. Considering mutations with a variant frequency ≥ 5%, 15.4% of patients showed at least one mutation (“NGS-positive”); the remaining had no mutations (“NGS-negative”). NGS status predicted the incidence of TEs: NGS-positive patients experienced a significantly higher rate of TEs compared to NGS-negative patients (66.6% vs. 18.2%, respectively; <i>p =</i> 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>NGS status represents an adjunctive risk factor for thrombosis in TN-PT and provides useful clinical information.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"47 5","pages":"869-876"},"PeriodicalIF":2.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797275","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}
Claus Vinter Bødker Hviid, Vibeke Staun Christensen, Klaus Rosenkilde Jensen, Julia Roman Møller, Anja Reinert Hansen
Objectives
Neonatal patients present a challenge to the clinical laboratory because of their low blood volume. The Sysmex XN-series features a predilution (PD) mode allowing hematologic measurements with only 20–50 μL of blood. We verified the PD mode for analysis of selected hematologic parameters in 50 μL microsamples.
Methods
Microsamples were prepared from adult EDTA blood. White blood cell count (leukocytes, neutrophils, and lymphocytes) and red blood cell parameters (erythrocytes, hemoglobin, hematocrit, mean cell volume, and reticulocytes) were evaluated. The imprecision of the PD mode was evaluated over 3 days, and the accuracy was assessed by method comparison with the standard whole blood mode. The effect of capillary sampling, microsample stability during storage, and pneumatic tube transportation was evaluated. Finally, the bias was reproduced in a small sample of pediatric patients.
Results
For white blood cells, the bias was ≤ 5.4% (95% CI: 4.5–6.2) and imprecision was below 3.5% (except at the lowest levels). Capillary sampling had little effect on PD analytical performance (bias ≤ 0.7% and imprecision ≤ 4.7%) and white blood cell counts were stable for 7 h at room temperature and after pneumatic tube transportation. The red blood cell parameters generally exceeded the allowable bias and imprecision. The bias of the pediatric samples remained within the 95% PI for the method comparison studies.
Conclusion
The PD mode has acceptable analytical performance and preanalytical stability for white blood cell counts but not for red blood cell parameters. It may offer a low-volume alternative for hematologic monitoring.
{"title":"Automated Red and White Blood Cell Counting in Capillary Microsamples by Sysmex-XN Predilution Mode","authors":"Claus Vinter Bødker Hviid, Vibeke Staun Christensen, Klaus Rosenkilde Jensen, Julia Roman Møller, Anja Reinert Hansen","doi":"10.1111/ijlh.14478","DOIUrl":"10.1111/ijlh.14478","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Neonatal patients present a challenge to the clinical laboratory because of their low blood volume. The Sysmex XN-series features a predilution (PD) mode allowing hematologic measurements with only 20–50 μL of blood. We verified the PD mode for analysis of selected hematologic parameters in 50 μL microsamples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Microsamples were prepared from adult EDTA blood. White blood cell count (leukocytes, neutrophils, and lymphocytes) and red blood cell parameters (erythrocytes, hemoglobin, hematocrit, mean cell volume, and reticulocytes) were evaluated. The imprecision of the PD mode was evaluated over 3 days, and the accuracy was assessed by method comparison with the standard whole blood mode. The effect of capillary sampling, microsample stability during storage, and pneumatic tube transportation was evaluated. Finally, the bias was reproduced in a small sample of pediatric patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For white blood cells, the bias was ≤ 5.4% (95% CI: 4.5–6.2) and imprecision was below 3.5% (except at the lowest levels). Capillary sampling had little effect on PD analytical performance (bias ≤ 0.7% and imprecision ≤ 4.7%) and white blood cell counts were stable for 7 h at room temperature and after pneumatic tube transportation. The red blood cell parameters generally exceeded the allowable bias and imprecision. The bias of the pediatric samples remained within the 95% PI for the method comparison studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The PD mode has acceptable analytical performance and preanalytical stability for white blood cell counts but not for red blood cell parameters. It may offer a low-volume alternative for hematologic monitoring.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"47 5","pages":"808-816"},"PeriodicalIF":2.3,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797080","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}
Filip Vrbacký, Martin Blažek, Ilona Fátorová, Karolína Šímová, Pavel Žák
Background
Despite all the effort, infections remain one of the major causes of morbidity and mortality in clinically ill patients, and novel diagnostic markers detecting infections in early stages are searched for. Intensive Care Infection Score (ICIS) was developed as such a marker.
Methods
A total of 102 patients admitted to intensive care units (ICU) in the University Hospital Hradec Kralove, Czech Republic were enrolled in this study. ICIS along with relevant biochemical markers (procalcitonin, C-reactive protein and Interleukin 6) was analyzed on the day of the admission. Individual parameters used to calculate ICIS were analyzed too. Infection was subsequently confirmed in 30 patients.
Results
ICIS predicted infections with the highest AUC (0.958) of all analyzed markers. The cut-off value (< 4) was selected as the value with the highest Youden index, and it predicted sepsis with high specificity (84.2%) and sensitivity (93.3%). Negative predictive value was very high too (96.8%). Positive predictive value was 71.8%.
Conclusions
ICIS is a reliable, cheap, fast, and simply interpretable score for the early identification of infection in patients admitted to ICUs. ICIS ≥ 4 predicts infection with high sensitivity, specificity, and negative predictive value.
{"title":"Intensive Care Infection Score (ICIS) is an Early Marker for Infection in Time of Admission to Intensive Care Units","authors":"Filip Vrbacký, Martin Blažek, Ilona Fátorová, Karolína Šímová, Pavel Žák","doi":"10.1111/ijlh.14468","DOIUrl":"10.1111/ijlh.14468","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite all the effort, infections remain one of the major causes of morbidity and mortality in clinically ill patients, and novel diagnostic markers detecting infections in early stages are searched for. Intensive Care Infection Score (ICIS) was developed as such a marker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 102 patients admitted to intensive care units (ICU) in the University Hospital Hradec Kralove, Czech Republic were enrolled in this study. ICIS along with relevant biochemical markers (procalcitonin, C-reactive protein and Interleukin 6) was analyzed on the day of the admission. Individual parameters used to calculate ICIS were analyzed too. Infection was subsequently confirmed in 30 patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ICIS predicted infections with the highest AUC (0.958) of all analyzed markers. The cut-off value (< 4) was selected as the value with the highest Youden index, and it predicted sepsis with high specificity (84.2%) and sensitivity (93.3%). Negative predictive value was very high too (96.8%). Positive predictive value was 71.8%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ICIS is a reliable, cheap, fast, and simply interpretable score for the early identification of infection in patients admitted to ICUs. ICIS ≥ 4 predicts infection with high sensitivity, specificity, and negative predictive value.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"47 4","pages":"707-712"},"PeriodicalIF":2.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775264","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}
Pablo Martínez, María Verónica Arrieta, Germán Alejandro Detarsio, Mariana Paula Raviola
Introduction
Laboratory testing is important for ensuring treatment effectiveness of hemophilia B. The most widely used laboratory test to measure factor IX (FIX) activity is the modified activated partial thromboplastin time (aPTT, one-stage clotting assay [OSA]). Concerns emerged about albutrepenonacog alfa (Idelvion) impact on laboratory measurement. We aimed to evaluate a product-specific calibration curve for determining the activity of Idelvion in Argentina.
Methods
In our nationwide, prospective, noninterventional study, a product-specific calibration standard (PCS) was prepared from a reconstituted vial. Commercial FIX-deficient plasma (FIXdp) spiked with Idelvion was used as a normal control (NC:0.7 IU/mL) and low control (LC:0.1 IU/mL). A drug-specific OSA calibration curve was constructed starting from 1.0 IU/mL, followed by serial dilutions. Thirteen different aPTT reagents were used.
Results
Thiry-six results from 27 Care Centers were retrieved. Median (interquartile range [IQR]) NC local standard human plasma (LSH) and NC PCSs were 0.48 IU/mL (0.38–0.92) and 0.72 IU/mL (0.58–0.82), respectively. Coefficients of variation (CVs) for NC LSH and PCS were 44.6% and 24.8%, respectively; recovery rates (± 20%) were 22% and 83%. Median LC LSH and PCS were 0.09 IU/mL (0.07–0.13) and 0.10 IU/mL (0.07–0.13), respectively; CVs for LC LSH and PCS were 104.8% and 24.7%. Recovery rates (±30%) were 58% and 89%.
Conclusion
Idelvion-specific calibration curve showed better performance and lower CV rates independently of the aPTT reagent or the platform used. Calibration using this specific standard might allow more laboratories to obtain acceptable FIX values when processing NC and LC levels and patients' plasmas.
{"title":"Performance of a Drug-Specific Calibration Curve for Monitoring Treatment With Albutrepenonacog Alfa: A Multicenter Study in Argentina","authors":"Pablo Martínez, María Verónica Arrieta, Germán Alejandro Detarsio, Mariana Paula Raviola","doi":"10.1111/ijlh.14469","DOIUrl":"10.1111/ijlh.14469","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Laboratory testing is important for ensuring treatment effectiveness of hemophilia B. The most widely used laboratory test to measure factor IX (FIX) activity is the modified activated partial thromboplastin time (aPTT, one-stage clotting assay [OSA]). Concerns emerged about albutrepenonacog alfa (Idelvion) impact on laboratory measurement. We aimed to evaluate a product-specific calibration curve for determining the activity of Idelvion in Argentina.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In our nationwide, prospective, noninterventional study, a product-specific calibration standard (PCS) was prepared from a reconstituted vial. Commercial FIX-deficient plasma (FIXdp) spiked with Idelvion was used as a normal control (NC:0.7 IU/mL) and low control (LC:0.1 IU/mL). A drug-specific OSA calibration curve was constructed starting from 1.0 IU/mL, followed by serial dilutions. Thirteen different aPTT reagents were used.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thiry-six results from 27 Care Centers were retrieved. Median (interquartile range [IQR]) NC local standard human plasma (LSH) and NC PCSs were 0.48 IU/mL (0.38–0.92) and 0.72 IU/mL (0.58–0.82), respectively. Coefficients of variation (CVs) for NC LSH and PCS were 44.6% and 24.8%, respectively; recovery rates (± 20%) were 22% and 83%. Median LC LSH and PCS were 0.09 IU/mL (0.07–0.13) and 0.10 IU/mL (0.07–0.13), respectively; CVs for LC LSH and PCS were 104.8% and 24.7%. Recovery rates (±30%) were 58% and 89%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Idelvion-specific calibration curve showed better performance and lower CV rates independently of the aPTT reagent or the platform used. Calibration using this specific standard might allow more laboratories to obtain acceptable FIX values when processing NC and LC levels and patients' plasmas.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"47 4","pages":"713-719"},"PeriodicalIF":2.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775266","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}
XiaoDong Zhao, JingXin Zhou, JinRong Yao, QiaoMei Shi, Jing Su, Na Hu
Introduction
Multiple myeloma (MM) is a highly lethal hematologic malignancy. Myeloid-derived suppressor cells (MDSCs) exert vital effects on myeloma cells in the bone marrow microenvironment. Macrophage migration inhibitory factor (MIF) is a chemokine-like inflammatory cytokine that can not only prevent the free movement of macrophages but also regulate innate and adaptive immune responses. This study intends to explore the relationship between MIF and MDSCs in the bone marrow microenvironment.
Methods
Single-cell RNA sequencing (scRNA-seq) analysis was performed based on the GSE124310 dataset (containing the MM and normal samples). Cell types were annotated using the feature genes collected from CellMarker 2.0. Ligand-receptor pairs for communication between MDSC subsets and other cells were inferred using CellChat. Characterizations of relevant cells were determined by flow cytometry.
Results
scRNA-seq analysis showed that 10 cellular subsets were annotated. Based on the differential expression of MIF, MDSCs were divided into two subsets, MIF+MDSCs and MIF−MDSCs. There was a difference in the ratios of MIF+MDSCs and MIF−MDSCs between the MM and Normal groups. Cell communication analysis showed that MIF+MDSCs and Plasma cells had low signal intensity in the RETN-CAP1 pathway, while MIF−MDSCs and Plasma cells had high signal intensity in the RETN-CAP1 pathway. Flow cytometry assay showed that RETN, Arg-1, and iNOS expression in MDSCs was significantly increased in the MM group compared with the normal group, and RETN, Arg-1, and iNOS expression was higher in MIF+MDSCs than that in MIF−MDSCs. CAP1 expression in Plasma cells was significantly elevated in the MM group compared with the Normal group.
Conclusion
MIF is high-expressed in MM patients and could be correlated with MDSCs in the bone marrow microenvironment.
{"title":"Single-Cell Transcriptome Analysis Reveals the Effect of MIF on Myeloid-Derived Suppressor Cells in Multiple Myeloma","authors":"XiaoDong Zhao, JingXin Zhou, JinRong Yao, QiaoMei Shi, Jing Su, Na Hu","doi":"10.1111/ijlh.14473","DOIUrl":"10.1111/ijlh.14473","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Multiple myeloma (MM) is a highly lethal hematologic malignancy. Myeloid-derived suppressor cells (MDSCs) exert vital effects on myeloma cells in the bone marrow microenvironment. Macrophage migration inhibitory factor (MIF) is a chemokine-like inflammatory cytokine that can not only prevent the free movement of macrophages but also regulate innate and adaptive immune responses. This study intends to explore the relationship between MIF and MDSCs in the bone marrow microenvironment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-cell RNA sequencing (scRNA-seq) analysis was performed based on the GSE124310 dataset (containing the MM and normal samples). Cell types were annotated using the feature genes collected from CellMarker 2.0. Ligand-receptor pairs for communication between MDSC subsets and other cells were inferred using CellChat. Characterizations of relevant cells were determined by flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>scRNA-seq analysis showed that 10 cellular subsets were annotated. Based on the differential expression of MIF, MDSCs were divided into two subsets, MIF<sup>+</sup>MDSCs and MIF<sup>−</sup>MDSCs. There was a difference in the ratios of MIF<sup>+</sup>MDSCs and MIF<sup>−</sup>MDSCs between the MM and Normal groups. Cell communication analysis showed that MIF<sup>+</sup>MDSCs and Plasma cells had low signal intensity in the RETN-CAP1 pathway, while MIF<sup>−</sup>MDSCs and Plasma cells had high signal intensity in the RETN-CAP1 pathway. Flow cytometry assay showed that RETN, Arg-1, and iNOS expression in MDSCs was significantly increased in the MM group compared with the normal group, and RETN, Arg-1, and iNOS expression was higher in MIF<sup>+</sup>MDSCs than that in MIF<sup>−</sup>MDSCs. CAP1 expression in Plasma cells was significantly elevated in the MM group compared with the Normal group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MIF is high-expressed in MM patients and could be correlated with MDSCs in the bone marrow microenvironment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"47 5","pages":"849-858"},"PeriodicalIF":2.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775268","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":"Acquisition of SETBP1 Mutation During Transformation of Mature Plasmacytoid Dendritic Cell Proliferation to Blastic Plasmacytoid Dendritic Cell Neoplasm in Chronic Myelomonocytic Leukemia","authors":"Mark Anthony Turingan, Cuihong Wei, Hong Chang","doi":"10.1111/ijlh.14475","DOIUrl":"10.1111/ijlh.14475","url":null,"abstract":"","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"47 4","pages":"756-759"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756801","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}
Ahmed Ahmed Allam, Heba A. Ahmed, Mohammad Ahmad Hassan, Safaa A. A. Khaled, Azza Shibl, Amira Mahmoud Osman, Nada Mohamed Rafat Ali, Nesma Mokhtar Ahmed
Introduction
This study aimed to assess programmed death-1 (PD-1) and programmed death ligand-1 (PDL-1) expression in newly diagnosed pediatric cases of acute B-lymphoblastic leukemia (B-ALL) and at 6 months of treatment and to explore their value as biomarkers.
Methods
Fifty newly diagnosed B-ALL patients and 30 controls were recruited. Bone marrow samples or peripheral blood were obtained from children at diagnosis and 6 months after cytotoxic therapy. Flow cytometric analysis of obtained samples was done and the PD-1, PDL-1, and CD3 (cluster of differentiation) expressions were recorded.
Results
Percentages of PD-1, PDL-1, and CD3 in the control and B-ALL groups at initial presentation were 7.9% ± 2.8% vs. 16.45% ± 7.7% (p = 0.023), 8.6% ± 3.4% vs. 19.05% ± 13.7% (p < 0.001), and 30.8% ± 1.2% vs. 11.05% ± 7.3% (p < 0.001), respectively. CD3 expression increased significantly at 6 months; PD-1 and PDL-1 expression showed insignificant decrease from initial presentation. There was a negative correlation between PD-1 and HB level (p = 0.03) and a positive correlation between PD-1 and PDL-1 at 6 months of treatment (p = 0.002). Remission rates increased significantly with the decrease of PD-1and PDL-1.
Conclusion
Initially, PD-1 and PDL-1 were higher in patients than in controls and decreased 6 months after treatment. PD-1 and PDL-1 expression was associated with increased remission rates, implicating that modulation of PD-1 and PDL-1 expression may be a therapeutic approach for B-ALL. Moreover, this study created a new method for the assessment of PD-1 and PDL-1 in B-ALL.
{"title":"Programmed Cell Death-1 and Programmed Cell Death Ligand-1 in Childhood Acute B-Lymphoblastic Leukemia: Expression and Significance as Biomarker","authors":"Ahmed Ahmed Allam, Heba A. Ahmed, Mohammad Ahmad Hassan, Safaa A. A. Khaled, Azza Shibl, Amira Mahmoud Osman, Nada Mohamed Rafat Ali, Nesma Mokhtar Ahmed","doi":"10.1111/ijlh.14472","DOIUrl":"10.1111/ijlh.14472","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>This study aimed to assess programmed death-1 (PD-1) and programmed death ligand-1 (PDL-1) expression in newly diagnosed pediatric cases of acute B-lymphoblastic leukemia (B-ALL) and at 6 months of treatment and to explore their value as biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifty newly diagnosed B-ALL patients and 30 controls were recruited. Bone marrow samples or peripheral blood were obtained from children at diagnosis and 6 months after cytotoxic therapy. Flow cytometric analysis of obtained samples was done and the PD-1, PDL-1, and CD3 (cluster of differentiation) expressions were recorded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Percentages of PD-1, PDL-1, and CD3 in the control and B-ALL groups at initial presentation were 7.9% ± 2.8% vs. 16.45% ± 7.7% (<i>p</i> = 0.023), 8.6% ± 3.4% vs. 19.05% ± 13.7% (<i>p</i> < 0.001), and 30.8% ± 1.2% vs. 11.05% ± 7.3% (<i>p</i> < 0.001), respectively. CD3 expression increased significantly at 6 months; PD-1 and PDL-1 expression showed insignificant decrease from initial presentation. There was a negative correlation between PD-1 and HB level (<i>p</i> = 0.03) and a positive correlation between PD-1 and PDL-1 at 6 months of treatment (<i>p</i> = 0.002). Remission rates increased significantly with the decrease of PD-1and PDL-1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Initially, PD-1 and PDL-1 were higher in patients than in controls and decreased 6 months after treatment. PD-1 and PDL-1 expression was associated with increased remission rates, implicating that modulation of PD-1 and PDL-1 expression may be a therapeutic approach for B-ALL. Moreover, this study created a new method for the assessment of PD-1 and PDL-1 in B-ALL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical Trial</h3>\u0000 \u0000 <p>\u0000 <b>Trial Registration:</b> NCT05428111</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"47 5","pages":"832-839"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756807","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}
Acute leukemias with hyperleukocytosis (> 100 × 109/L) can produce cytoplasmic blast fragments that interfere with platelet counts, notably in impedance-based methods, potentially masking severe thrombocytopenia and increasing hemorrhagic risk. While fluorescent platelet counting (PLT-F) is promoted as platelet-specific, its accuracy in the presence of blast fragments remains uncertain.
Methods
This retrospective study analyzed 269 blood samples from 87 patients with hypercellular acute leukemia. Blast fragments were identified on blood smears. Platelet counts by impedance were compared to optical (PLT-O) and fluorescent (PLT-F) methods when available. Flow cytometry (FC) quantification by CD41+/CD61+ staining was performed in selected cases.
Results
Blast fragments were observed in 26% of cases, predominantly in AML-M5 and AML-M1 subtypes. In the absence of blast fragments, PLT-I, PLT-O, and PLT-F showed comparable results. However, in samples with blast fragments, PLT-I frequently overestimated platelet counts compared to PLT-O and PLT-F. PLT-F counts were closer to FC quantification but still overestimated platelet numbers in 6 of 16 samples with FC results, particularly in cases of severe leukocytosis. Notably, PLT-F failed to trigger abnormal scattergram flags in all but one of the discrepant cases. PLT-O provided results comparable to PLT-F in most cases with blast fragments but also demonstrated limitations in select cases.
Conclusion
PLT-O and PLT-F methods both have limitations in hypercellular acute leukemias with blast fragments. FC remains the most reliable approach when blast fragments are present. Routine blood smear evaluations are essential for detecting interferences and ensuring accurate thrombocytopenia assessment in these high-risk patients.
{"title":"Overestimation of Automated Platelet Counts by Blast Fragments in Acute Hypercellular Leukemias: A Retrospective Study Comparing Impedance, Optical (PLT-O), Fluorescent (PLT-F), and CD41/CD61 Flow Cytometry Methods","authors":"Victor Bobée, Romain Ravel-Chapuis, Maïssa Souissi, Catherine Boutet, Dany Bigot, Cédric Paquin, Jorel Gruchet, Virginie Barbay, Vincent Camus, Elsa Bera, Sylvie Daliphard","doi":"10.1111/ijlh.14464","DOIUrl":"10.1111/ijlh.14464","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Acute leukemias with hyperleukocytosis (> 100 × 10<sup>9</sup>/L) can produce cytoplasmic blast fragments that interfere with platelet counts, notably in impedance-based methods, potentially masking severe thrombocytopenia and increasing hemorrhagic risk. While fluorescent platelet counting (PLT-F) is promoted as platelet-specific, its accuracy in the presence of blast fragments remains uncertain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study analyzed 269 blood samples from 87 patients with hypercellular acute leukemia. Blast fragments were identified on blood smears. Platelet counts by impedance were compared to optical (PLT-O) and fluorescent (PLT-F) methods when available. Flow cytometry (FC) quantification by CD41+/CD61+ staining was performed in selected cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Blast fragments were observed in 26% of cases, predominantly in AML-M5 and AML-M1 subtypes. In the absence of blast fragments, PLT-I, PLT-O, and PLT-F showed comparable results. However, in samples with blast fragments, PLT-I frequently overestimated platelet counts compared to PLT-O and PLT-F. PLT-F counts were closer to FC quantification but still overestimated platelet numbers in 6 of 16 samples with FC results, particularly in cases of severe leukocytosis. Notably, PLT-F failed to trigger abnormal scattergram flags in all but one of the discrepant cases. PLT-O provided results comparable to PLT-F in most cases with blast fragments but also demonstrated limitations in select cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PLT-O and PLT-F methods both have limitations in hypercellular acute leukemias with blast fragments. FC remains the most reliable approach when blast fragments are present. Routine blood smear evaluations are essential for detecting interferences and ensuring accurate thrombocytopenia assessment in these high-risk patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"47 4","pages":"622-631"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756805","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}
Madeleen Bosma, Richard M. Noordervliet, Mercedeh Tajdar, Christine van Laer
{"title":"Verification of an Algorithm for Detection of Unstable Haemoglobin Variants With Sysmex XN-10 Yielded a High Degree of False Positives","authors":"Madeleen Bosma, Richard M. Noordervliet, Mercedeh Tajdar, Christine van Laer","doi":"10.1111/ijlh.14467","DOIUrl":"10.1111/ijlh.14467","url":null,"abstract":"","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"47 4","pages":"748-749"},"PeriodicalIF":2.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756810","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}
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