Peripheral Blood Counts Research Articles

Immune endotyping and gene expression profile of patients with chronic rhinosinusitis with nasal polyps in the aspirin-exacerbated respiratory disease (AERD) and the non-AERD subgroups

BackgroundChronic Rhinosinusitis (CRS) is a paranasal sinus inflammatory disease and is divided into two subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays a T helper (Th)2 biased phenotype, and based on sensitivity or tolerance to aspirin or non-steroidal anti-inflammatory drugs (NSAID), is further subdivided into Aspirin-exacerbated respiratory disease (AERD) and non-AERD groups. Considering the challenge of diagnosis and treatment in patients with CRSwNP, particularly the AERD subtype, and the significance of endotyping in these patients, we examined the immune profile and endotyping based on gene expression analysis in the AERD and the non-AERD groups of patients with CRSwNP.Material and methodIn this study, 21 patients were enrolled and were categorized into AERD (N = 10) and non-AERD (N = 11) groups based on their sensitivity to aspirin. After the special washing period, nasal polyps were biopsied in both groups, and the infiltration of eosinophils, neutrophils, plasma cells, and lymphocytes was compared between the AERD and the non-AERD groups. Also, gene expression levels of transcription factors including Tbet, GATA3, RoRγt, and FoxP3 and inflammatory cytokines including interleukin (IL)1β, IL1RAP (IL1 receptor accessory protein), IL2, IL4, IL5, IL10, IL13, IL17, TNFα, and IFNγ were investigated by quantitative Real-time PCR (qRT-PCR). Statistical analyses were performed using analytical tests including Kolmogorov–Smirnov, Mann-Whitney, and T-test. A P value less than 0.05 was considered statistically significant.ResultsThe mean ± SD age of the studied groups was 37 ± 8.7 years old (21–50) for the AERD, and 40.4 ± 7.7 years old (31–52) for the non-AERD. LMS/EPOS/SNOT scores and pulmonary function tests showed no difference between the two groups. Serum immunoglobulin E (IgE) levels were found to be higher in patients with AERD (p = 0.04), however, the peripheral blood counts of eosinophils were comparable in the two groups. In the histopathologic analysis, the AERD group showed higher percentages of eosinophils (p = 0.04), neutrophils (p = 0.04), and plasma cells (p = 0.04) than the non-AERD group. Additionally, the gene expression levels of GATA3 (p = 0.001), IL4 (p = 0.04), IL5 (p = 0.007), and IL17 (p = 0.03) were significantly higher in the AERD than the non-AERD groups.ConclusionHigher gene expression levels of GATA3, IL4, IL5, and IL17 were observed in the AERD group compared with the non-AERD group. These findings point to distinct patterns of inflammation in patients with AERD, with a predominance of Th2 inflammation.

A systematic review and meta-analysis on absolute eosinophil counts and the risk of asthma in preschool children with wheezing: An EAACI Task Force Report.

Preschool children with wheezing disorders pose diagnostic and therapeutic challenges and consume substantial healthcare resources. Peripheral eosinophil blood count (EBC) has been proposed as a potential indicator for future asthma development. This review by the European Academy of Allergy and Clinical Immunology (EAACI) Preschool Wheeze Task Force aimed to provide systematic evidence for the association between increased EBC and the risk of future asthma, as well as to identify potential cutoff values. In February 2023, a search of PubMed, EMBASE, and Cochrane Library databases was conducted to identify studies comparing EBCs in preschool children with wheezing who continued to wheeze later in life and those who did not. Included observational studies focused on children aged <6 years with a wheezing disorder, assessment of their EBCs, and subsequent asthma status. No language or publication date restrictions were applied. Among the initial 3394 studies screened, 10 were included in the final analysis, involving 1225 patients. The data from these studies demonstrated that high EBC in preschool children with wheezing is associated with future asthma development, with odds ratios of 1.90 (95% CI: 0.45-7.98, p = .38), 2.87 (95% CI: 1.38-5.95, p < .05), and 3.38 (95% CI: 1.72-6.64, p < .05) for cutoff values in the <300, 300-449, and ≥450 cells/μL ranges, respectively. Defining a specific cutoff point for an elevated EBC lacks consistency, but children with EBC >300 cells/μL are at increased risk of asthma. However, further research is needed due to the limitations of the included studies. Future investigations are necessary to fully elucidate the discussed association.

Circulating basophils in patients with type IIb autoimmune chronic spontaneous urticaria have a lower histamine content

AbstractBackgroundPatients suffering from chronic spontaneous urticaria (CSU) are typically classified as type I or type IIb autoimmune CSU, but further patient stratification is hindered by the lack of biomarkers.ObjectivesWe investigated whether the histamine content of individual basophils differ between patient subtypes in CSU to evaluate its potential as a biomarker.MethodsA total of 101 patients diagnosed with CSU were included in the study. The histamine content per circulating basophil was derived from the basophil count in peripheral blood and levels of total cellular blood histamine. These measures, together with results from the serum‐induced basophil histamine release assay (s‐BHRA), were correlated to information on demographics, clinical characteristics, patient reported outcomes and laboratory analyses.ResultsThe histamine content per basophil was significantly different between s‐BHRA positive and ‐negative patients (0.175 vs. 1.40 pg/cell, p &lt; 0.001) and showed a significant negative correlation to the degree of basophil activation in s‐BHRA (ρ = −0.209, p = 0.036). Furthermore, the amount of histamine in individual basophils was found to be significantly correlated with levels of total cellular blood histamine (ρ = 0.376, p &lt; 0.001), eosinophil counts (ρ = 0.205, p = 0.040), levels of thyroid stimulating hormone (ρ = −0.246, p = 0.014) and titre of antibodies against thyroid peroxidase (ρ = −0.216, p = 0.031) and thyroglobulin (ρ = −0.203, p = 0.044).ConclusionsLow content of intracellular histamine in circulating basophils is associated with known markers of type IIb autoimmune CSU. Further studies are required to assess whether the amount of histamine in basophils can be used to monitor or predict response to treatment in patients.

Zhisou powder suppresses airway inflammation in LPS and CS-induced post-infectious cough model mice via TRPA1/TRPV1 channels

Ethnopharmacological relevanceZhisou Powder (ZSP), a traditional Chinese medicine (TCM) prescription, has been widely used in the clinic for the treatment of post-infectious cough (PIC). However, the exact mechanism is not clear. Aim of the studyThe aim of this study was to investigate the ameliorative effect of ZSP on PIC in mice. The possible mechanisms of action were screened based on network pharmacology, and the potential mechanisms were explored through molecular docking and in vivo experimental validation. Materials and methodsLipopolysaccharide (LPS) (80μg/50 μL) was used to induce PIC in mice, followed by daily exposure to cigarette smoke (CS) for 30 min for 30 d to establish PIC model. The effects of ZSP on PIC mice were observed by detecting the number of coughs and cough latency, peripheral blood and bronchoalveolar lavage fluid (BALF) inflammatory cell counts, enzyme-linked immunosorbent assay (ELISA), and histological analysis. The core targets and key pathways of ZSP on PIC were analyzed using network pharmacology, and TRPA1 and TRPV1 were validated using RT-qPCR and western blotting assays. ResultsZSP effectively reduced the number of coughs and prolonged the cough latency in PIC mice. Airway inflammation was alleviated by reducing the expression levels of the inflammatory mediators TNF-α and IL-1β. ZSP modulated the expression of Substance P, Calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) in BALF. Based on the results of network pharmacology, the mechanism of action of ZSP may exert anti-neurogenic airway-derived inflammation by regulating the expression of TRPA1 and TRPV1 through the natural active ingredients α-spinastero, shionone and didehydrotuberostemonine. ConclusionZSP exerts anti-airway inflammatory effects through inhibition of TRPA1/TRPV1 channels regulating neuropeptides to alleviate cough hypersensitivity and has a favorable therapeutic effect on PIC model mice. It provides theoretical evidence for the clinical application of ZSP.

Evaluation of immature granulocyte percentage and count in pediatric nephrotic syndrome

ABSTRACT Objective The importance of immature granulocytes (IGs) in most infectious and inflammatory diseases has been highlighted. This study aimed to determine the clinical usability and importance of changes in the peripheral complete blood count profile, including IG percentage (IG%) and IG count (IG#), during the relapse and remission phases in pediatric nephrotic syndrome (NS) patients. Methods This retrospective observational study was performed at a tertiary care hospital between February 2020 and August 2022. Demographic characteristics and laboratory parameters were recorded. The IG count and IG% were measured using an automated hematological analyzer. Results IG% and IG# were both higher during the relapse phase of NS than during the remission phase (0.29% ± 0.14%, versus 0.23% ± 0.14%, p = 0.037 and 0.027 ± 0.015 × 103/µL, versus 0.018 ± 0.014 × 103/µL, p = 0.005, respectively). The neutrophil to lymphocyte ratio (NLR), platelet (PLT), white blood cell (WBC), and neutrophil counts had a strong positive correlation with IG# (r = 0.397, p < 0.001; r = 0.352, p < 0.001; r = 0.622, p < 0.001; r = 0.660, p < 0.001, respectively). The NLR, PLT, WBC, and neutrophil counts had a strong positive correlation with IG% (r = 0.348, p < 0.001; r = 0.187, p = 0.039; r = 0.303, p = 0.001; r = 0.426, p < 0.001, respectively). Receiver operating characteristic curve analysis showed that IG# had the best AUC value of 0.69 (95% CI: 0.58–0.77; p = 0.001) for the relapse phase of NS with a cutoff value of 0.025 × 103/µL (sensitivity: 81.0%, specificity: 78.1%). Conclusions It is probable that a high level of immature granulocyte count has a positive correlation for NS relapse in pediatric patients. The IG % and IG# can be used together as biomarkers of inflammation in pediatric NS relapse.

Clinical, genomic and immune microenvironmental determinants of nivolumab response in head and neck squamous cell carcinoma.

In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC. The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing. Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses. Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.

Relationship between serum procalcitonin level and severity and prognosis in patients with traumatic brain injury in plateau areas

To analyze the changes rule of serum procalcitonin (PCT) levels in patients with traumatic brain injury in plateau areas, and to evaluate its value in assessing the severity and prognosis of the patients. A prospective cohort study was conducted. The patients with traumatic brain injury admitted to the critical care medicine departments of Xining Third People's Hospital (at an altitude of 2 260 metres) and Golmud City People's Hospital (at an altitude of 2 780 metres) from May 2018 to September 2022 were enrolled. According to the Glasgow coma scale (GCS) score at admission, the patients were divided into mild injury group (GCS score 13-15), severe injury group (GCS score 9-12), and critical injury group (GCS score 3-8). All patients received active treatment. Chemiluminescence immunoassay was used to measure the serum PCT levels of patients on the 1st, 3rd, 5th, and 7th day of admission. The Kendall tau-b correlation method was used to analyze the correlation between serum PCT levels at different time points and the severity of the disease. The patients were followed up until October 30, 2022. The prognosis of the patients was collected. The baseline data of patients with different prognosis were compared. The Cox regression method was used to analyze the relationship between baseline data, serum PCT levels at different time points and prognosis. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of serum PCT levels at different time points for death during follow-up. Finally, a total of 120 patients with traumatic brain injury were enrolled, including 52 cases in the mild injury group, 40 cases in the severe injury group, and 28 cases in the critical injury group. The serum PCT levels of patients in the mild injury group showed a continuous downward trend with the prolongation of admission time. The serum PCT levels in the severe injury and critical injury groups reached their peak at 3 days after admission, and were significantly higher than those in the mild injury group (μg/L: 3.53±0.68, 4.47±0.63 vs. 0.40±0.14, both P < 0.05), gradually decreasing thereafter, but still significantly higher than the mild injured group at 7 days. Kendall tau-b correlation analysis showed that there was a significant positive correlation between serum PCT levels on days 1, 3, 5, and 7 of admission and the severity of disease (r value was 0.801, 0.808, 0.766, 0.528, respectively, all P < 0.01). As of October 30, 2022, 92 out of 120 patients with traumatic brain injury survived and 28 died, with a mortality of 23.33%. Compared with the survival group, the GCS score, serum interleukin-6 (IL-6) levels, white blood cell count (WBC) in peripheral blood, and PCT levels in cerebrospinal fluid at admission in the death group were significantly increased [GCS score: 5.20±0.82 vs. 4.35±0.93, IL-6 (ng/L): 1.63±0.45 vs. 0.95±0.27, blood WBC (×109/L): 14.31±2.03 vs. 11.95±1.98, PCT in cerebrospinal fluid (μg/L): 11.30±1.21 vs. 3.02±0.68, all P < 0.01]. The serum PCT levels of patients in the survival group showed a continuous downward trend with prolonged admission time. The serum PCT level in the death group peaked at 3 days after admission and was significantly higher than that in the survival group (μg/L: 4.11±0.62 vs. 0.52±0.13, P < 0.01), gradually decreasing thereafter, but still significantly higher than the survival group at 7 days. Cox regression analysis showed that serum IL-6 levels [hazard ratio (HR) = 17.347, 95% confidence interval (95%CI) was 5.874-51.232], WBC in peripheral blood (HR = 1.383, 95%CI was 1.125-1.700), PCT levels in cerebrospinal fluid (HR = 1.952, 95%CI was 1.535-2.482) at admission and serum PCT levels on admission days 1, 3, 5, and 7 [HR (95%CI) was 6.776 (1.844-24.906), 1.840 (1.069-3.165), 3.447 (1.284-9.254), and 6.666 (1.214-36.618), respectively] were independent risk factors for death during follow-up in patients with traumatic brain injury (all P < 0.05). ROC curve analysis showed that the AUC of serum PCT levels on days 1, 3, 5, and 7 for predicting death during follow-up in patients with traumatic brain injury was all > 0.8 [AUC (95%CI) was 0.898 (0.821-0.975), 0.800 (0.701-0.899), 0.899 (0.828-0.970), 0.865 (0.773-0.958), respectively], indicating ideal predictive value. The optimal cut-off value for serum PCT level at 3 days of admission was 1.88 μg/L, with the sensitivity of 78.6% and specificity of 88.0% for predicting death during follow-up. Abnormal expression of serum PCT levels in patients with traumatic brain injury on the 3rd day of admission was found. The serum PCT levels greater than 3 μg/L may be related to severe illness. The serum PCT levels greater than 1.88 μg/L can predict the poor prognosis of patients. Dynamic observation of changes in serum PCT levels has good evaluation value for the severity and prognosis of patients with traumatic brain injury in plateau areas.

Assessment of tolerance of a new product (gluten-free grain snack) in children with food allergy to gluten

The development of a technological scheme for the production of cereal snacks based on the extrusion process with preliminary enzymatic treatment of wheat flour and the use of hydrolysate as a partial replacement for gluten-free raw materials is an urgent task. The use of gluten-free cereal snacks in the diet opens up new possibilities for dietary therapy in patients suffering from various manifestations of food allergy to gluten, making their diet more diverse and meeting their individual needs. The purpose of the research was to clinically evaluate the tolerance of gluten-free cereal snacks in children with PA to gluten. Material and methods. The study included 21 patients (male and female) aged 3 to 17 years with a diagnosed food allergy, including gluten. All children received gluten-free cereal snacks according to their age: children from 3 to 7 years old (n=11) received 50 g (176 kcal) daily, and children aged 8 to 17 years old (n=10) received 100 g (352 kcal) daily for 14 days, in addition to a non-specific hypoallergenic diet excluding highly allergenic foods. On the first day of the study, the patients or one of their parents evaluated the organoleptic properties of the presented product (taste, color, smell) using a 5-point scale (1 - very bad, 5 - excellent), according to a specially designed questionnaire. The assessment of clinical symptoms over time related to skin, gastrointestinal tract, and nervous system was conducted using a second questionnaire, where parents kept a daily «observation log» reflecting the child's well-being and condition, as well as adverse events associated with taking the product. Clinical safety parameters were assessed based on the dynamics of complete blood count and blood immunological parameters (total IgE, specific IgE, and IgG4 antibodies to the studied allergens) at the beginning and end of the consumption period. Results. Daily examinations and patient questionnaires revealed no adverse reactions to the product. No significant differences in body weight were observed at the end of the study (p>0.05). In the results of clinical and immunological blood analysis before and after consuming gluten-free cereal snacks, no significant deviations were observed in the form of an increase in eosinophil count, total IgE, allergen-specific IgE and IgG4 antibodies in peripheral blood. This suggests a favorable clinical safety profile of the proposed product. Conclusion. The study found that consumption of the new product (gluten-free cereal snacks) was well-tolerated by children aged 3 to 17 years with various manifestations of food allergy: no adverse effects of the product or exacerbations of the underlying disease were observed during the 14-day period of gluten-free cereal snack consumption. Therefore, the studied gluten-free cereal snacks can be recommended for children aged 3 to 17 years with various manifestations of gluten FA, in combination with a gluten free diet.

Predictive Value of Pretreatment Neutrophil to Albumin Ratio in Response to Neoadjuvant Chemotherapy of Breast Cancer.

The immune system appears to play a crucial role in how breast cancer responds to chemotherapy. In this study, we investigated a peripheral marker of immune and inflammation named the neutrophil to albumin ratio (NAR) to explore its potential relationship with pathological complete response (pCR) in locally advanced breast cancer patients who underwent neoadjuvant chemotherapy (NAC). We conducted a retrospective analysis of 212 consecutive breast cancer patients who received NAC. The NAR was calculated by examining the complete blood cell count and albumin level in peripheral blood before starting NAC. Through ROC curve analysis, we determined the optimal cutoff value for NAR as 0.0877. We used Pearson's chi-square test or Fisher's exact test to evaluate the relationship between NAR and pCR, as well as other clinical and pathological characteristics. Logistic regression models were employed for univariate and multivariate analyses. The results of both univariate and multivariate logistic regression analyses showed that NAR was associated with tumor pathological regression. The NAR high group had a higher pCR rate compared to the NAR low group (OR 3.127 [95% CI 1.545-6.328]; p = 0.002). According to this study, it was observed that patients with breast cancer who had high levels of NAR were more likely to achieve pCR when undergoing NAC.

Analysis of Correlation between Blood Inflammation Indicators in Peripheral Blood and Prognosis of Patients with Multiple Myeloma.

This study aimed to investigate the value of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) in the prognosis of patients with multiple myeloma (MM). Before treatment, the NLR and LMR and all clinical indicators of 168 patients, diagnosed with MM at the Affiliated Hospital of Southwest Medical University from April 2013 to April 2022, were retrospectively analyzed, and the patients were grouped according to their median NLR counts and median LMR counts. Differences between the groups were compared by using the chi-squared (χ²) test, the Kaplan-Meier survival curve and Log-rank test were used for survival analysis and difference comparison, and the COX proportional risk model was constructed to analyze the factors affecting the prognosis of the MM patients. The test level was α = 0.05. The groups were divided into high NLR group (> 2.19) and low NLR group (≤ 2.19) and high LMR group (> 3.45) and low LMR group (≤ 3.45), according to the median NLR and LMR values. The clinical stage, blood β2 microglobulin, and serum creatinine levels in the high NLR group were higher than in the low NLR group, and the differences between the groups were statistically significant (p < 0.05). The clinical stage and blood β2 microglobulin in the low LMR group were higher than in the high LMR group, and the differences between the groups were statistically significant (p < 0.05). The Cox univariate and multivariate analyses showed that peripheral blood NLR < 2.19 and LMR ≤ 3.45 were independent risk factors for the prognosis in patients with MM (p < 0.05). High NLR and low LMR counts of peripheral blood suggest a poor prognosis; NLR and LMR may be prognostic indicators in MM patients.

KEMİK İLİĞİ METASTAZI OLAN SOLİD MALİGNİTELİ HASTALARDA KLİNİK VE LABORATUVAR PARAMETRELERİNİN ÖNEMİ-TEK MERKEZ DENEYİMİ

Objective: Bone marrow biopsy is an efficient and reliable diagnostic procedure for the identification of bone marrow involvement. In recent years, bone marrow examination has become more helpful in documenting the metastatic involvement of malignancies.&#x0D; Method: Patients with solid tumors and anomalies in hematological parameters had their peripheral blood morphology examined at our facility. Each instance included information on the patient's peripheral blood counts, peripheral blood morphology, and prior therapies. The purpose of this study was to analyze bone marrow biopsy and aspiration for unexplained hematological abnormalities in solid cancer patients and to look into the pathological findings, clinical and hematological laboratory features, and outcomes of such patients in our facility. Additionally, we provided information on the treatment and prognosis of these patients.&#x0D; Results: When compared to the group that had bone marrow biopsy involvement, the lower RDW-Cv value in the former group was shown to be statistically significant (p=0.005; p

Acute myeloid leukaemia masquerading as transverse myelitis

Acute myeloid leukaemia (AML) is known to cause paraneoplastic transverse myelitis. However, the direct invasion or extramedullary compression of the spinal cord is rare unlike in the case of chronic lymphocytic leukaemia. We report the case of a young man presenting with transverse myelitis who was found to have leukaemic infiltrates on neuroimaging. The uniqueness of this being the first presentation of the patient with AML in the form of epidural infiltrates in the absence of peripheral blood count abnormalities. This highlights the importance of neuroimaging to delineate associated conditions in a suspected patient with transverse myelitis.

Relation between Systemic Inflammatory Index (SII) and Hair Trace Elements, Metals and Metalloids Concentration in Epicardial Coronary Artery Disease-Preliminary Report.

Coronary artery atherosclerosis development and progression are related to generic, clinical, and lifestyle factors combined with inflammatory activation. The relationship between trace element concentration and morbidity is under investigation to gain a clearer understanding of underlying pathological processes. Thirty-five consecutive patients (22 males and 13 females) with a median [interquartile range (IQR)] age of 67 (61-73) years presenting with anginal symptoms were included in the single center prospective analysis in 2022 and divided into a epicardial coronary artery disease (CAD) and non-CAD group. Scalp hair chemical analysis and inflammatory markers from a peripheral blood count were analyzed. The correlation analysis of elements and inflammatory indexes showed statistical significance between median hair lithium (Li) concentration and the systemic inflammatory index (SII) (r = -0.476, p = 0.046), antimony (Sb) (r = -0.521, p = 0.028) followed by chromium (Cr) (r = -0.478, p = 0.045) and iron (Fe) (r = -0.604, p = 0.008) in the CAD group. Similar correlations were not found in non-CAD group. The correlation between scalp hair lithium (Li), antimony (Sb), chromium (Cr) and iron (Fe) concentration and the systemic inflammatory index (SII) were revealed only in patients with coronary artery disease. Our analysis identified a strong correlation between inflammatory activation and iron concentration.

Predictive role of monocyte count for significant coronary artery disease identification in patients with stable coronary artery disease.

The coronary artery disease (CAD) remains the leading cause of morbidity that is characterized by broad spectrum of symptoms. Up to 30% of performed angiographies reveal normal coronary arteries. The aim of the study was to find simple predictor for significant epicardial artery stenosis among patients with chronic coronary syndrome. There were 187 patients (131 (709%) men and 56 (30%) women) in the median (Q1-Q3) age of 67 [58-72] presenting with stable CAD symptoms enrolled into the present retrospective analysis. The demographical, clinical and laboratory characteristics between patients with normal and significant coronary artery stenosis were compared. The multivariable analysis revealed coexistence of hypercholesterolemia as significant differentiation factor (odds ratio [OR]: 4.38, 95% confidence interval [CI]: 1.78-10.80, p = 0.001) for significant CAD and inverse relation to serum high density lipoprotein (OR: 0.19, 95% CI: 0.05-0.72, p = 0.015) and relation to creatinine concentration (OR: 1.03, 95% CI: 1.00-1.05, p = 0.012). Among whole peripheral blood count analysis, the significant relation was noticed to be hemoglobin concentration (OR: 1.09, 95% CI: 1.10-1.18, p = 0.022) and monocyte count (OR: 32.3, 95% CI: 1.09-653.6, p = 0.017). Receiver operator curve revealed (AUC: 0.641, p = 0.001) with the optimal cut-off value above 0.45 K/uL for monocyte, yelding sensitivity of 81.82% and specificity of 58.06%. The peripheral monocyte count above 0.45 k/uL may be considered as a predictor of significant coronary artery disease in symptomatic patients with chronic coronary syndrome.

Time of Attainment of Clinical Remission and Peripheral Blood Count Recovery during Induction Chemotherapy for Childhood Acute Lymphoblastic Leukemia

Background: Acute lymphoblastic leukemia(ALL) is the most common pediatric malignancy. Infection and bleeding are the leading cause of death during induction chemotherapy in childhood ALL. So, proper knowledge about anticipated infection and bleeding are very important during this period. But the duration of clinical remission and recovery of peripheral blood count during induction chemotherapy is not well reported in literature. Objective: The aim of the study was to determine the time of attainment of clinical remission and recovery of peripheral blood count after initiation of induction chemotherapy and to determine if the duration of clinical remission and peripheral blood count recovery differs between therapeutic risk groups. Methods: This prospective observational study was conducted from January 2021 to December 2021 in the Department of Paediatric Haematology and Oncology, BSMMU. Newly diagnosed admitted Eighty-Six ALL of both sexes aged 1 to 17.9 years were included. After commencing chemotherapy, physical examination was recorded every day until clinical remission and complete blood count (CBC) was recorded one to two days interval until peripheral blood count recovery. The number of packed red blood cell (PRBC) and platelet transfusions and the number of days of intravenous antibiotics were recorded. Results: Mean duration of clinical remission, complete Hemoglobin (Hb), Absolute neutrophil count(ANC) and platelet recovery was 8.4 ± 4.5 days, 25±7.9 days, 23.3±5.6 days and 21.8±6.4 days respectively (p&lt;0.01). Time to attain partial recovery of platelet was 14.0±4.9 days in high risk and 19.2±5.3 days in standard risk group. PRBC transfusion requirement was 2.2±1.2 units in high risk group and 1.7±0.8 units in standard risk group (p&lt;0.05). Time to attain partial recovery of ANC, number of days with I/V antibiotics and duration of treatment interruption were higher in high risk group. Conclusion: Time of clinical remission was similar between risk group. Platelet recovery occurred earlier than Hemoglobin (Hb) and absolute neutrophil count (ANC) recovery. Transfusion and supportive care requirement were more in high risk group during induction chemotherapy. So, more supportive care should be arranged up to three weeks of induction period to increase survival of high risk childhood ALL. Bangladesh Med Res Counc Bull 2023; 49: 177-182

Rapid Progression of Myelodysplastic/Myeloproliferative Neoplasm with Neutrophilia to Acute Myeloid Leukemia: A Case Report

Abstract Introduction/Objective Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with neutrophilia, formerly atypical chronic myeloid leukemia, is a subtype of MDS/MPN that is characterized by peripheral blood neutrophilia with frequent left-shifted myeloid cells, dysplastic granulocytes, and an absence of the Philadelphia chromosome or BCR- ABL1 fusion gene. Its clinical course is variable, ranging from a chronic indolent disease to an aggressive leukemia. Herein, we report a case of who was diagnosed with MDS/MPN with neutrophilia and had rapid progression to acute myeloid leukemia. Methods/Case Report A 63-year-old male patient with no significant medical history presented with incidental findings of abnormal peripheral blood counts: leukocytosis of 153 × 109/L, platelets of 82 × 109/L, and Hb of 6.7g/dl. Flow cytometry (FCM) on peripheral blood was significant for increased granulocytes and a population of aberrant blasts (~7.3%) expressing CD5, CD11c, CD13, CD34, CD38, CD56 (partial), CD117, and HLA-DR. The initial Bone marrow biopsy showed a hypercellular marrow (90-100%), 3% blasts, dysgranulopoiesis, and dysmegakaryopoiesis. Fluorescence in situ hybridization (FISH) analysis for BCR-ABL1 fusion and MPN with Eosinophilia panel, including FIP1L1-CHIC2-PDGFRA; PDGFRB/5q33; FGFR1/8p12, were all negative. Next Generation sequencing (NGS) detected at least one variant of strong clinical significance (Tier I) including: ASXL1 c.1900_1922del23, NRAS c.35G&amp;gt;C, U2AF1 c.470A&amp;gt;C, potential clinical significance (Tier II) GATA2 c.1160_1165delCCATGA and unknown clinical significance (Tier III) SETBP1 c.2620G&amp;gt;A. The chromosomal analysis showed trisomy 14. The patient received Decitabine for 2 months, but follow-up FCM on the subsequent bone marrow examination revealed 40% blasts, with marked erythroid hyperplasia. The patient was diagnosed with acute myeloid leukemia. Despite receiving Venetoclax and Azacitidine, the patient deteriorated and expired in 10 months after the initial diagnosis of MDS/MPN with neutrophilia. Results (if a Case Study enter NA) NA Conclusion This case highlights the poor prognosis associated with MDS/MPN with neutrophilia. Optimal management strategies for these patients are still evolving, and new targeted therapies are needed to improve outcomes.

Development of a Multi-Organ Radiation Injury Model with Precise Dosimetry with Focus on GI-ARS.

The goal of this study was to establish a model of partial-body irradiation (PBI) sparing 2.5% of the bone marrow (BM2.5-PBI) that accurately recapitulates radiological/nuclear exposure scenarios. Here we have reported a model which produces gastrointestinal (GI) damage utilizing a clinical linear accelerator (LINAC) with precise dosimetry, which can be used to develop medical countermeasures (MCM) for GI acute radiation syndrome (ARS) under the FDA animal rule. The PBI model (1 hind leg spared) was developed in male and female C57BL/6 mice that received radiation doses ranging from 12-17 Gy with no supportive care. GI pathophysiology was assessed by crypt cell loss and correlated with peak lethality between days 4 and 10 after PBI. The radiation dose resulting in 50% mortality in 30 days (LD50/30) was determined by probit analysis. Differential blood cell counts in peripheral blood, colony forming units (CFU) in bone marrow, and sternal megakaryocytes were analyzed between days 1-30, to assess the extent of hematopoietic ARS (H-ARS) injury. Radiation-induced GI damage was also assessed by measuring: 1. bacterial load (16S rRNA) by RT-PCR on days 4 and 7 after PBI in liver, spleen and jejunum, 2. liposaccharide binding protein (LBP) levels in liver, and 3. fluorescein isothiocyanate (FITC)-dextran, E-selectin, sP-selectin, VEGF, FGF-2, MMP-9, citrulline, and serum amyloid A (SAA) levels in serum. The LD50/30 of male mice was 14.3 Gy (95% confidence interval 14.1-14.7 Gy) and of female mice was 14.5 Gy (95% confidence interval 14.3-14.7 Gy). Secondary endpoints included loss of viable crypts, higher bacterial loads in spleen and liver, higher LBP in liver, increased FITC-dextran and SAA levels, and decreased levels of citrulline and endothelial biomarkers in serum. The BM2.5-PBI model, developed for the first time with precise dosimetry, showed acute radiation-induced GI damage that is correlated with lethality, as well as a response to various markers of inflammation and vascular damage. Sex-specific differences were observed with respect to radiation dose response. Currently, no MCM is available as a mitigator for GI-ARS. This BM2.5-PBI mouse model can be regarded as the first high-throughput PBI model with precise dosimetry for developing MCMs for GI-ARS under the FDA animal rule.

Increase of Dnts Correlated with Clinic Outcome after Allogeneic DNT Cells Infusion in r/r AML Patients

Background: The treatment of relapsed/refractory AML (r/r AML) patients are still an unmet medical need in clinic. In recent years, cellular immunotherapy especially CAR-T cell therapy played more important roles in hematological malignancies. Unfortunately, the safety and efficacy of existing cell therapies to r/r AML patients still facing many challenges and needs to be further improved. Our previous studies have demonstrated that Double Negative T cells (DNTs) showed strong cytotoxicity to AML blasts and can improve the prognosis of AML patients relapsed after allogeneic stem cell transplantation. Here, we reported our ongoing phase I clinical trial of RC1012 injection (allogeneic DNT cells) in patients with r/r AML (NCT05471323). This study protocol was approved by Chinese NMPA (National Medical Products Administration). Informed consent was obtained in accordance with the Declaration of Helsinki. Objective: Explore the efficacy indicator in r/r AML patients after allogeneic DNT cells therapy. Methods: 7 patients with r/r AML were enrolled in the trial according to the inclusion and exclusion criteria. DNTs from peripheral blood of healthy donors were manufactured in GMP facility. After lymphodepleting chemotherapy with fludarabine and cyclophosphamide, each patient received three infusions of HLA-mismatched DNT cells at 1.5×10^8 cells/kg with one week interval. The PK data were collected and analyses as well as the checkpoint inhibitors on T cells was monitored. Results: As reported before, DNT cells had shown good safety profile in the treatment of r/r AML. Multiple infusions of allogeneic DNT cells can benefit some patients with r/r AML. Allogeneic DNT cell therapy can stimulate the patient's DNT cells to proliferate, and the DNT cells level in peripheral blood corelated to the disease outcomes. Allogeneic DNT cells can also stimulate the patient's CD4 and CD8 cells to proliferate and is favorite the CD8 cells to grow, indicating its potential to enhance the anti-tumor activities after DNT cells therapy. Allogeneic DNT cells have no toxicity to normal bone marrow cells, and the quick recovery of platelet counts in peripheral blood corelated to the efficacy of the DNT cells therapy. TIGIT, PD-1, CD57 are increased on patients' T cells which may hinder the effect of immunotherapy in r/r AML patients. Conclusions: Allogeneic DNTs therapy are safe in clinical treatment and can reduce tumor burden after infusion with the increase of patient's DNT cells in complete remission and partial remission patients. These findings warrant the allogeneic DNTs as a novel adjuvant therapy with allo-HSCT to enhance the treatment efficacy in r/r AML. The finding of TIGIT, PD-1, CD57 molecules were increased on patients' T cells indicated that the combination of DNTs with immune checkpoint inhibitors may further improve the DNTs efficacy in r/r AML patients. Key words: Double negative T cells (DNTs), AML, Immunotherapy

The Diagnostic Value of Circulating Blasts in Patients with Myeloproliferative Neoplasms in Accelerated or Blast Phase

Introduction: Myeloproliferative neoplasms (MPNs) are progressive cancers with variable propensity to transform to accelerated phase and blast phase (APBP), an acute leukemia-equivalent state. MPN in APBP is associated with very poor prognosis with shortened survival and is notorious for poor response to therapy. The only curative therapy is allogeneic stem cell transplant. Blast phase is defined by 20% blasts or higher in the bone marrow biopsy (BMBx) or peripheral blood (PB), while accelerated phase is defined by blast percentage 10% or higher. The diagnosis, and response to therapy often requires serial BMBx and PB testing. There is recognition of excessive circulating PB blasts in MPNs that occasionally exceeds blast count in BMBs, especially in fibrotic bone marrow. The aim of this study is to investigate the correlation between PB and BMBx blasts, and if PB testing might be a more convenient and lest costly marker for diagnosis and response assessment of MPN in APBP. Methods: This is a cross sectional study, based on single institution retrospective chart review. Subjects included all available subjects over the age of 18, diagnosed with APBP MPN between January 1, 2017, to July 1, 2022. We collected serial blast percentages in simultaneously collected BMBx and PB samples, assessed by the same hematopathologist. We also collected baseline disease characteristics upon transformation to APBP. This is reported descriptively, and statistically analyzed for significance using a paired t-test. Results: 15 subjects and 54 paired BP and BMBx blast assessments were identified. Median age was 59 (range 30 -71) and median duration since MPN diagnosis was 48 months (1-420). Median OS of the cohort since APBP diagnosis was 10 months. BMBx fibrosis was Grade II-III in 13/15 patients. Cytogenetic and mutation profiles, and therapies delivered are listed on Table 1. Based on evaluation of the results, there was no statistical correlation between blasts in the PB and BMBx both prior to therapy, and during therapy (detailed biostatistical analysis will be provided during ASH presentation) Conclusions: Patients with APBP MPN undergo frequent diagnostic testing, including a bone marrow biopsy, to evaluate the percentage of blasts in the bone marrow. Quantification of blast count in peripheral blood should not be as a standalone diagnostic lab test for APBP MPN. BMBx remains essential for this diagnosis, response assessment, as well as cytogenetic and molecular profiling. The outcomes on APBP remain poor despite utilization of modern targeted therapeutics.

The Impact of Leukapheresis Collection on Patients Undergoing Chimeric Antigen T-Cell Receptor Therapy with Tisagenlecleucel

Introduction Autologous chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of acute lymphoblastic leukemia (ALL) in children and young adolescents, with an impressive overall remission rate of 81% in patients with relapsed or refractory (r/r) disease 1. Approved by the US FDA, tisagenlecleucel (Kymriah ®) is now approved for patients up to 25 years of age with pre B -cell ALL that is refractory or in second or later relapse as well as adult patients with r/r non-Hodgkin lymphoma (NHL) including diffuse large B cell lymphoma (DLBCL) after two or more lines of systemic therapy 2. Apheresis is the first step of CAR-T cell manufacturing with the recommended collection goal of ≥1.0x10 9 CD3 cells or ≥2.0x10 9 total nucleated cells (TNC) 3. However, this crucial process can be affected by technical and patient specific factors, including heavily pre-treated patients, resulting in CAR T-cell manufacture failure rates of 1-14% in clinical trials 4, 5, 6, 7. The clinical impact of CD3+ count in peripheral blood at the time of leukapheresis and optimal apheresis collection parameters remain to be established. Methods: This is a retrospective study of patients 0-88 years with r/r DLBCL or ALL who underwent leukapheresis between August 31 st 2017 to August 1 st, 2022 for tisagenlecleucel therapy. Spearman correlation was conducted to evaluate the association between absolute lymphocyte count (ALC) and cell counts prior to leukapheresis. The Kaplan-Meier method was employed to evaluate overall survival (OS) and event-free survival (EFS) from date of CAR-T. Cox proportional hazards regression analysis was utilized to examine the associations between OS or EFS and measures of interest, including white blood cell count (WBC), ALC, CD3+ cells from leukapheresis, CD3+%, cell viability, viable T cells %, total cell count, IFNγ CD19, maximum cytokine release syndrome (CRS) score (Max CRS), maximum immune effector cell-associated neurotoxicity syndrome (ICANS) score (Max ICANS), duration of CRS, duration of ICANS, and post-CART transplantation. Results: Forty patients were included, 22 (55%) patients were male, and the median age at apheresis was 50 years (5-88 years). There were significant positive correlations between ALC and the CD3+ cells from leukapheresis (Correlation: 0.62 [0.33 - 0.83], p-value &amp;lt;0.001) and CD3+ % (Correlation: 0.46 [0.001 - 0.78], p-value 0.020). For the 39 patients with data available, the median OS was 94.2 months (95% CI: 55.3 - 129.1). For EFS from date of CAR-T, the median survival from the date of diagnosis until the date of first recurrence event (relapse, secondary malignancy, and death) or the last follow-up date was 75.1 months (95% CI: 34.7 - 104.5). Based on univariate survival analysis results, there was no significant association observed between OS or EFS and the variables of interest. The median IFNγ reported on certificate of analysis from manufacturer was 162 (13-818) with 14 (36%) patients maximum grade CRS equal to 0, and 27 (69%) maximum grade ICANS equal to 0. For those who experienced any grade of CRS, there was a significant correlation with CD3+ cells (p-value 0.007) but not significant when compared to IFNγ (p-value 0.51). There was no significant correlation between those who experienced ICANS compared to CD3+ cells (p-value 0.17) or IFNγ (p-value 0.1). There was no significant positive correlations between IFNγ and the duration CRS (Correlation: 00.292 [-0.045, 0.554], p-value 0.07) or duration of ICANS (Correlation: 0-0.241 [-0.531, 0.064], p-value 0.16). Of note, we had one patient who had a manufacturing failure and unfortunately passed away before second round of apheresis. For this patient, WBC on apheresis was 4.3k/microL, ALC was 560 and CD3+ cells was 84.4%. Conclusion: A significant positive correlation was observed between ALC and the CD3+ cells as well as its percentage from leukapheresis for pediatric and adult patients undergoing tisagenlecleucel CAR-T. However, no significant effects were found when detecting the association between ALC with OS or EFS. In addition, there were no significant findings between IFNγ and the duration of CRS or ICANS. Funding: This work was supported in part by the NIH/NCI Cancer Center Support Grant (award number P30 CA016672) and used the Biostatistics Resource Group.