Absolute Lymphocyte Count Research Articles

Construction and Evaluation of a Model for the Prediction of Risk Factors Associated with Severe Pneumonia in Patients with Positive Hepatitis B Core Antibody and COVID-19 Infection in China

Background: Hepatitis B virus (HBV) infection is a high-risk factor for severe COVID-19 cases, leading clinicians to enhance the monitoring of patients with concurrent HBV and COVID-19 infections. However, this focus is typically on patients with active HBV infection. Patients who are HBV surface antigen (HBsAg) negative and HBV core antibody (anti-HBc) positive are often considered to have either a past infection that has naturally cleared or to be in a low-replication state, and thus receive less clinical attention. However, in immunosuppressed states, such as during immunosuppressive treatment following COVID-19 infection, the virus in these patients may reactivate. In such cases, this reactivation can increase the risk of COVID-19 progressing to a severe illness. Therefore, being HBsAg negative and anti-HBc positive could be a potential risk factor for severe COVID-19. Studying the combination of anti-HBc positivity and COVID-19 infection can help identify high-risk populations, allowing for the implementation of targeted prevention and management measures, thereby reducing the occurrence of severe COVID-19 cases. Objectives: To establish and evaluate a model for predicting severe pneumonia in patients with positive anti-HBc combined with COVID-19 infection. Methods: We retrospectively enrolled 380 patients who tested positive for anti-HBc, negative for HBsAg, and HBV e-antigen (HBeAg), combined with COVID-19 infection, in our hospital from December 2022 to May 2023. Based on the inclusion criteria, 163 patients were included in the study. We applied the Lasso binary logistic regression model to optimize feature selection, identifying eight non-zero coefficients using a minimum of one standard error. Using the multiple logistic regression method with backward selection, we screened six factors from the eight selected by the Lasso binary logistic regression model. These six factors were used to construct the predictive model and a nomogram. The validity of our nomogram was assessed using the area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow (HL) test, and decision-curve analysis (DCA). Results: Hypertension, diabetes, decreased absolute lymphocyte count, prolonged prothrombin time, elevated aspartate aminotransferase, and decreased albumin are high-risk factors for severe pneumonia in patients with positive anti-HBc combined with COVID-19 infection. The AUC of the predictive model constructed using these six factors is 0.785, with a 95% confidence interval of (0.709-0.862). The HL test, performed using the calibration curve, yielded a p-value of 0.868. The application of this diagnostic curve will increase the net benefit when the threshold probability is between 5% and 75%. Conclusions: The constructed nomogram can be used to predict the risk of patients with positive anti-HBc combined with COVID-19 infection progressing to severe pneumonia, based on routine blood parameters, liver function, coagulation, lactate dehydrogenase levels, and the patient's underlying disease. The predictive model demonstrates good discrimination, calibration, and clinical utility.

Sustained lymphocyte decreases after treatment for early breast cancer

The role of adaptive immunity in long-term outcomes in early breast cancer is increasingly recognised. Standard (neo)adjuvant chemotherapy can have adverse effects on immune cells. We conducted a retrospective longitudinal study of full blood counts (FBC) of 200 patients receiving (neo)adjuvant chemotherapy for early breast cancer at a single institution. FBC results at four time points from pre-treatment to 12 months post-chemotherapy were analysed. Flow cytometry was performed for patients with matched pre- and post-chemotherapy peripheral blood mononuclear cell samples. A significant decrease in absolute lymphocyte count at 12 months post-chemotherapy was observed (p < 0.01), most pronounced in pre-menopausal patients (n = 73; p < 0.01), patients receiving dose-dense chemotherapy regimens (n = 60; p < 0.01) and patients receiving adjuvant radiotherapy (n = 147, p < 0.01). In pre-menopausal patients, significant changes in CD4+ T cells subsets post-chemotherapy were observed. Further investigation, including long-term clinical outcomes, is needed to meaningfully improve long-term anti-tumour immunity.

A practical approach to febrile cancer patients: Diagnostic stewardship in Oncology units

Introduction Cancer and cytotoxic chemotherapy used for its treatment predispose to severe and often fatal infections. Prompt diagnosis and timely antibiotic therapy are crucial, with delays in therapy initiation having high mortality. Complete blood count (CBC) is an inexpensive, standardized, and preliminary investigation for the management and follow-up of cancer patients with diagnostic and prognostic value. Method We studied the types of infections associated with various cancers treated with chemotherapy, their etiologies and susceptibility patterns, and the hematological profile of these patients as predictors of infection. Results A total of 21 patients (12 solid and 9 hematological malignancies) presented with 31 febrile episodes. White Blood cell count (2079 cells/cu. mm), percentage of neutrophils (52.9%), absolute neutrophil (137.5 cells/cu. mm), and platelet count (1,77,507 cells/cu. mm) were significantly lower in the 11 patients with febrile neutropenia. The absolute lymphocyte count (412.7 cells/cu. mm) was reduced with a strikingly low Neutrophil-to-lymphocyte ratio (NLR) (6.07) in patients with neutropenia. Laboratory and radiological evidence were present in 14/15 episodes of hematological malignancies (p-0.218) whereas unexplained clinical sepsis was common in solid malignancies (p-0.0202). The majority of documented infections were bacterial, caused by gram-negative bacilli, often showing multi-drug resistance. Infectious etiologies were identified in 71.4% of the patients with febrile neutropenia for &gt;5days. Bacterial infections developed within 2 days of neutropenia, whereas viral and fungal infections manifested in prolonged neutropenia. Multi-site infections and higher mortality rates were observed in patients with febrile neutropenia. (p&lt;0.04) Conclusion Febrile neutropenia is a common complication among patients receiving chemotherapy for cancer, with an increased risk of morbidity and mortality. Early, rapid, and accurate diagnosis is key to prompt intervention. Hematological parameters such as Total Leukocyte count, platelet count, NLR, and Platelet-to-lymphocyte ratio are promising biomarkers in conjunction with morphological changes in neutrophils, thus proving that CBC and peripheral smears are simple, easily available, cost-effective, and highly dependable screening tools, especially in resource-poor settings.

Diagnostic Value of Osteopontin, Lymphocyte-to-Monocyte Ratio, and CA-125 in Ovarian Carcinoma Suspect

Osteopontin (OPN) is an important protein in cancer development and progressivity. Lymphocyte-to-Monocyte Ratio (LMR) as a systemic immunity and inflammatory indicator could be an ideal predictor biomarker because of its method’s simplicity and availability. Elevated CA-125 and OPN as well as decreased LMR were reported as signs of ovarian malignancy. Limited studies about OPN and LMR as diagnostic biomarkers, as well as various specificity and sensitivity of CA-125 intrigued the researcher to prove OPN, LMR, and CA-125 as diagnostic biomarkers for ovarian carcinoma. This study aimed to measure the diagnostic value of OPN, LMR, and CA-125 levels against histopathology results for ovarian carcinoma diagnosis. Eighty patients involved with suspected ovarian carcinoma who were referred to Dr. Kariadi Hospital, Semarang. Osteopontin and CA-125 levels were measured using ELISA, and LMR was calculated from absolute lymphocyte and monocyte counts using an automated hematology analyzer. The receiver operating characteristics curve was used to determine the cut-off and 2x2 table. The cut-off values for OPN, LMR, and CA-125 were 124 ng/mL, 3.7 and 45.4 U/mL, respectively. The sensitivity for OPN, LMR, and CA-125 was 67.24%, 62.07% and 60.34%. Specificity for OPN, LMR, and CA-125 were 68.18%, 54.55% and 59.09%. Osteopontin is the best parameter for determining the diagnosis of ovarian carcinoma but it is still not sufficient because OPN cut-off was still within the normal reference value.

Plasma Cell Leukemia with atypical CCND1/IGH fusion and Monocytoid morphology; A Rare Case Finding

Abstract Introduction/Objective Plasma cell leukemia (PCL) is a rare and aggressive form of plasma cell dyscrasia, often presenting as a variant of multiple myeloma (MM). It is characterized by the presence of ≥5% circulating plasma cells in peripheral blood, either as a primary or secondary manifestation of MM. Methods/Case Report Our case is of a 77-year-old male who presented with epigastric tenderness and bi-basilar crackles. Laboratory results showed severe hypercalcemia, elevated creatinine, leukocytosis, and elevated absolute neutrophil and lymphocyte counts. Imaging revealed widespread lytic lesions in the ribs, scapulae, thoracolumbar spine, and bony pelvis. Peripheral blood smear showed significant macrocytic anemia with rare polychromatophilic cells, numerous immature plasmacytoid cells (&amp;gt;20% of total cell count) and monocytoid morphology. Flow cytometry confirmed a population of monotypic plasma cells (28% of total cells). Bone marrow biopsy revealed a hypercellular plasma cell infiltrate with complex clonal karyotypic abnormalities, including the t(11;14)(q13;q32), rearrangements of 1p, and gain of 1q. FISH analysis showed an atypical CCND1/IGH fusion in 57% of cells, with one fusion, two orange (CCND1), and two green (IGH) signals. The case presented demonstrates a rare instance of an atypical CCND1/IGH fusion in plasma cell leukemia with monocytoid morphology, which poses diagnostic challenges. Prompt and accurate diagnosis is essential for managing the condition, given its consistently poor prognosis despite advancements in therapy over the past decade. Results (if a Case Study enter NA) NA Conclusion Our case highlights the importance of recognizing rare molecular abnormalities in PCL and suggests that further research into the molecular pathways involved in the disease is needed to improve diagnosis, treatment options and clinical outcomes.

Optimization of culture conditions for HBV-specific T cell expansion in vitro from chronically infected patients

BackgroundHepatitis B virus (HBV) clearance depends on an effective adaptive immune response, especially HBV-specific T cell-mediated cellular immunity; however, it is difficult to produce enough HBV-specific T cells effectively.ResultsIn this work, we investigated the proportions of stimulated cells, serum, and culture media as the three primary factors to determine the most effective procedure and applied it to HLA-A2 (+) people. In parallel, we also examined the correlation between clinical parameters and HBV-specific immunity. Concerning amplification efficiency, 4 × 105 cells stimulation was superior to 2 × 106 cells stimulation, AIM-V medium outperformed 1640 medium, and fetal bovine serum (FBS) exceeded human AB serum under comparable conditions. As expected, this procedure is also suitable for developing HBV-specific CD8 + T cells in HLA-A2(+) individuals. Expanded HBV-specific T cell responses decreased with treatment time and were negatively correlated with HBV DNA and HBsAg. Furthermore, the number of HBV-specific IFN-γ + SFCs was strongly correlated with the ALT level and negatively correlated with the absolute lymphocyte count and the ALB concentration.ConclusionsWe confirm that stimulating 4 × 105 PBMCs in AIM-V medium supplemented with 10% FBS is the best approach and that HBeAg, HBsAg, and ALB are independent predictors of HBV-specific T-cell responses.

Prognostic factors and risk-stratification model of recurrent or metastatic head and neck squamous cell carcinoma treated with cetuximab containing regimen

BackgroundIn recent years, the addition of cetuximab to chemotherapy has improved treatment outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this study, we present the real-world survival data of R/M HNSCC patients who received cetuximab-containing regimens from thirteen medical centers in Taiwan, as well as a three-level risk stratification model for this patient population.MethodsThis study enrolled R/M HNSCC patients from thirteen medical centers in Taiwan who received cetuximab-containing regimens from January 1, 2017 to June 6, 2022. The cases were divided into a training cohort and a validation cohort based on the start of treatment. Overall survival (OS) was evaluated in both cohorts and exploratory analysis was performed to identify associated adverse clinical and laboratory factors. The results of the exploratory analysis were used to construct a three-level risk stratification prediction model for OS.ResultsA total of 1434 patients with R/M HNSCC were enrolled in this study and received cetuximab-containing regimens. The overall population had a median OS of 8.57 months (95% CI: 8.07 – 9.08). Multivariate analysis of the training cohort identified poor ECOG performance status, heavy alcohol consumption, and prior adjuvant CCRT or lack of prior RT as adverse prognostic factors. Comparison of laboratory data between patients with OS≦6 and OS > 6 also revealed unfavorable factors, including increased white blood cell count, decreased hemoglobin level, increased platelet count, increased absolute neutrophil count, decreased absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio. Using forward prediction, a three-level risk stratification prediction model was constructed using the variables of ECOG performance status, alcohol consumption, skin metastasis, modality of radiation therapy, hemoglobin level, and neutrophil-to-lymphocyte ratio. The median OS in the low-risk, intermediate-risk, and high-risk groups were 12.02 months (95% CI 10.44–13.61), 7.5 months (95% CI 7.33–8.17), and 4.01 months (95% CI 3.94–4.08), respectively, with a log-rank test p-value < 0.001.ConclusionThis study presents a three-level risk stratification model with strong prediction ability for OS in R/M HNSCC patients who received cetuximab-containing regimens. The results are based on real-world data and may provide valuable information for clinicians in treatment planning and future drug development.

Machine Learning to Predict Interim Response in Pediatric Classical Hodgkin Lymphoma Using Affordable Blood Tests

PURPOSE Response assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers. METHODS Changes in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL. DS 1-3 denoted rapid early response (RER) while DS 4-5 denoted slow early response (SER). Missing values were imputed using the k-nearest neighbor algorithm. Baseline and follow-up blood test values were combined into a single difference variable. Data were split into training and testing sets for analysis using Python scikit-learn 1.2.2 with logistic regression, random forests, naïve Bayes, and support vector machine classifiers. RESULTS Random forest analysis achieved the best validated test accuracy of 73% when predicting RER or SER from blood samples. When applied to the full data set, the optimal model had a predictive accuracy of 80% and a receiver operating characteristic AUC of 89%. The most predictive variable was the differences in ALC, contributing 21% to the model. Differences in ferritin, LDH, and TWC contributed 15%-16%. Differences in ESR, hemoglobin, and albumin contributed 11%-12%. CONCLUSION Changes in low-cost, widely available blood tests may predict chemosensitivity for pediatric cHL without access to PET-CT, identifying patients who may not require radiotherapy. Changes in these nonspecific blood tests should be assessed in combination with clinical findings and available imaging to avoid undertreatment.

EP.14B.03 Predictive Value of Neutrophil-to-Lymphocyte Ratio (NLR) and Absolute Lymphocyte Count (ALC) In Thymic Epithelial Tumors

EP.14B.03 Predictive Value of Neutrophil-to-Lymphocyte Ratio (NLR) and Absolute Lymphocyte Count (ALC) In Thymic Epithelial Tumors

Systemic Inflammatory Response Index and the Short-Term Functional Outcome of Patients with Acute Ischemic Stroke: A Meta-analysis.

The systemic inflammatory response index (SIRI) is a novel indicator of systemic inflammation derived from the absolute counts of neutrophils, monocytes, and lymphocytes. The aim of this meta-analysis was to evaluate the association between SIRI and functional outcome in patients with acute ischemic stroke (AIS). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in this meta-analysis. Relevant cohort studies were retrieved by a search of electronic databases including PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure from database inception to February 9, 2024. A poor functional outcome was defined as a modified Rankin Scale ≥ 3 within 3months after disease onset. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. The protocol of the meta-analysis was not prospectively registered in PROSPERO. Fourteen cohort studies were included. Pooled results showed that a high SIRI at admission was associated with increased risk of poor functional outcome within 3months (odds ratio [OR]: 1.57, 95% confidence interval: 1.39 to 1.78, p < 0.001; I2 = 0%). Results of the meta-regression analysis suggested that the cutoff for defining a high SIRI was positively related to the OR for the association between SIRI and the risk of poor functional outcome (coefficient = 0.13, p = 0.03), while other variables including sample size, mean age, severity of stroke at admission, percentage of men, current smokers, or patients with diabetes did not significantly modify the results. Subgroup analyses according to study design, main treatments, and study quality scores showed similar results. A high SIRI may be associated with a poor functional outcome in patients after AIS.

Development and Validation of a Clinical Prediction Model for Paclitaxel Hypersensitivity Reaction on the Basis of Real-World Data: Pac-HSR Score.

Paclitaxel is effective chemotherapy against various cancers but can cause hypersensitivity reaction (HSR). This study aimed to identify predictors associated with paclitaxel HSR and develop a clinical prediction model to guide clinical decisions. Data were collected from the medical records database of Rajavithi Hospital. Patients with cancer treated with paclitaxel from 2015 to 2022 were included, and a multivariable logistic regression analysis identified predictors associated with paclitaxel HSR. The scoring system was transformed and calibrated on the basis of diagnostic parameters. Discrimination and calibration performances were assessed. Internal validation was conducted using bootstrap resampling with 1,000 replications. This study involved 3,708 patients with cancer, with an incidence of paclitaxel HSR of 10.11%. An 11-predictor-based Pac-HSR scoring system was developed, involving the following factors: younger age; poor Eastern Cooperative Oncology Group performance status; previous history of paclitaxel HSR; medication allergy history; chronic obstructive airway disease; lung and cervical cancers; high actual dose of paclitaxel; no diphenhydramine premedication; low hemoglobin level; high WBC count; and high absolute lymphocyte count. The C-statistics was 0.73 (95% CI, 0.70 to 0.76), indicating acceptable discrimination. The P value of the Hosmer-Lemeshow goodness-of-fit test was 0.751. The ratio of observed and expected values was 1.00, indicating good calibration. At a cutoff point of 8, specificity was 75.28% and sensitivity was 57.07%. Internal validation indicated good performance with minimal bias, and decision curve analysis demonstrated improved prediction with the use of this scoring system in clinical decision making. This study developed the 11-predictor-based Pac-HSR scoring system for predicting paclitaxel HSR in patients with cancer. High-risk patients identified by this score should be prioritized for close monitoring and early treatment prophylaxis.

Evaluation of Neutrophil to Lymphocyte Ratio with Neurological Severity and Short-Term Outcome in Acute Ischemic Stroke

Introduction: Stroke represents a significant global health care challenge, ranking as the second most common cause of mortality and disability worldwide. Inflammatory process plays an important role in pathophysiology of acute ischemic stroke. These inflammatory responses increase the brain damage and cause neurological deterioration. Neutrophils and lymphocytes serve as pivotal mediators of inflammatory response. Aims and Objectives: This study aims to evaluate the association between the Neutrophils to lymphocyte ratio (NLR) with the initial severity of stroke and the short-term functional outcome using the NIHSS and BARTHEL index respectively. Materials and Methods: We conducted an observational cross-sectional study on 80 patients admitted at Father Muller Medical College Hospital, which is a tertiary care centre in Mangalore between May 2023 to April 2024. Diagnosis of stroke was based on clinical evaluation and Radiological imaging. Peripheral blood samples were collected for complete blood count within 24 hours of stroke onset. The NLR was determined by dividing the absolute neutrophil count (ANC) to the absolute lymphocyte count (ALC). This was then correlated with the NIHSS and the BARTHEL index. Results: This study included 80 patients, with the mean age of 65.1 years. Majority of the patients were in the age group 51-70years (55%). The mean NLR was found to be 13.39. The mean NIHSS and BARTHEL index was 11.08 and 63.69 respectively. The NLR showed significant correlation with the initial stroke severity and the short-term functional outcomes. For the purpose of correlation NLR was divided into three groups i.e. &gt;3, 3-5 and &gt;5. Patients with higher NLR (&gt;5) were more likely to have a severe stroke and greater dependency. Conversely, those with lower NLR (&lt;3) had a minor stroke and slight dependency. 80% of the patients with severe stroke had a NLR above 5, while 82% of the patients with minor stroke had a NLR below 3 (p value &lt;0.001). This study also found a strong correlation between NIHSS and the BARTHEL index - patients with lower NIHSS and NLR were found to have a better short term function outcome. Conclusion: NLR was found to be significantly associated with the initial severity of stroke and the shortterm functional outcome. Because of its high specificity, low cost, routine use NLR can be used for the prediction of severity of stroke and patients can be prioritised for specialised treatment thus reducing the mortality rates.

Association between Preoperative Neutrophil-lymphocyte Ratio and All-cause Mortality in Patients Treated with Thoracic Endovascular Aortic Repair for Degenerative Thoracic Aortic Aneurysm

The neutrophil-lymphocyte ratio (NLR) has been increasingly recognized as a reliable surrogate marker for predicting mortality in clinical practice. This study determined the predictive ability of NLR for overall mortality after thoracic endovascular aortic repair (TEVAR) for degenerative thoracic aortic aneurysm (TAA). Data from patients treated with TEVAR for degenerative TAA at our university hospital from January 2013 to December 2021 were evaluated. The preoperative NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. One hundred-three patients were included in this study. During a 9-year follow-up, 32 patients (31.1%) died. Multivariable analyses showed that age (hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.00-1.12; p = 0.021), ischemic heart disease (HR, 2.13; 95% CI, 1.05-4.36; p = 0.038), and NLR (HR, 1.36; 95% CI, 1.08-1.72; p = 0.009) predicted all-cause mortality after TEVAR. A receiver operating characteristic curve determined the optimal cut-off value of NLR to predict all-cause mortality was 3.48. An elevated preoperative NLR is indicative of a higher likelihood of all-cause mortality in patients treated with TEVAR for degenerative TAA, suggesting that NLR could serve as a possible biomarker for stratifying patients at risk of overall mortality after TEVAR.

Abstract C019: Peripheral Absolute Lymphocyte Count and Breast Cancer Mortality among Racially Diverse Women

Abstract Background: Among patients with triple-negative breast cancer (TNBC), higher tumor infiltrating lymphocytes (TILs) are associated with increased overall mortality (OM) and breast cancer-specific mortality (BCSM). We previously found that low peripheral absolute lymphocyte count (ALC) is associated with increased OM and BCSM in a sample of mostly non-Hispanic White (NHW) patients with TNBC. Here, we investigated the association between low ALC and mortality (OM and BCSM) across different breast cancer subtypes and whether the association is potentially modified by race and ethnicity. Methods: We used the Oncoshare database, which links electronic medical records (EMRs) data to the California Cancer Registry (CCR), and assessed women diagnosed with stage I-III breast cancer between 2000-2017, who had at least one ALC measurement and treated at two healthcare systems in California. Patient and tumor characteristics were obtained from the CCR and laboratory testing from EMRs. Patients with metastatic disease and chemotherapy receipt after one year of diagnosis were excluded. Multivariable logistic models assessed factors associated with “low ALC” (&amp;lt;1 K/µL, ever vs. never). We applied Cox models to evaluate the association between “min ALC” (lowest ALC value after diagnosis) and OM and BCSM within each breast cancer subtype (Luminal A, HER2-enriched, and TNBC), and further explored the interaction between min ALC and race and ethnicity. All models adjusted for low absolute neutrophil count, demographics, and tumor features. Results: Among 10,750 women analyzed, the risk of “low ALC” was associated with TNBC vs Luminal A (odds ratio (OR) 1.22, p=0.0098), older age (OR 1.01 per year, p&amp;lt;0.001), higher grade (grade 3 vs. 1, OR 1.15, p=0.042), higher stage (stage III vs. I, OR 1.81, p&amp;lt;0.001), and public vs. private health insurance (OR 1.29, p&amp;lt;0.001). Cox models showed that higher min ALC was associated with lower OM across breast cancer subtypes (Luminal A: HR 0.37, HER2-enriched: HR 0.32, TNBC: HR 0.22; all p&amp;lt;0.001) and BCSM (Luminal A: HR 0.29, HER2-enriched: HR 0.23, TNBC: HR 0.19; all p&amp;lt;0.001). Interaction analysis showed that race and ethnicity modified the association between min ALC and OM (interaction-p &amp;lt;0.001) and BCSM (interaction-p &amp;lt; 0.001) in the overall cohort; compared to NHW women (HR 0.38, 95% confidence interval [0.34-0.43]), the association between min ALC and OM was stronger among Hispanic (HR 0.24, [0.18-0.33]), Asian (HR 0.19, [0.14-0.25]), and Black (HR 0.21, [0.13-0.35]) women. Similar results were observed for BCSM. Conclusions: Low peripheral ALC, a routinely measured clinical lab result, strongly predicts higher BCSM and OM across breast cancer subtypes, beyond TNBC. The association between min ALC and BCSM/OM was stronger among Black and Asian women vs. NHW women, suggesting that maintaining normal ALC during breast cancer treatment may reduce BCSM and OM, especially for women from racial and ethnic minoritized groups. Future research should investigate differences in ALC, immune response, and BCSM in diverse populations. Citation Format: Candice N. Thompson, Ingrid Luo, Mina Satoyoshi, Lidia Schapira, Esther M. John, Summer S. Han, Allison W. Kurian. Peripheral Absolute Lymphocyte Count and Breast Cancer Mortality among Racially Diverse Women [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C019.

Absolute lymphocyte count predicts efficacy of palbociclib in patients with metastatic luminal breast cancer

BackgroundAbsolute lymphocyte count (ALC) is a predictive and prognostic factor for various tumor types, including breast cancer. Palbociclib is a CDK4/6 inhibitor widely used for the treatment of metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer. However, predictive biomarkers of the efficacy of palbociclib remain unelucidated. We conducted a retrospective study to examine the predictive value of the baseline ALC in patients treated with palbociclib.MethodsThe medical records of patients with ER-positive, HER2-negative breast cancer treated with palbociclib plus hormonal therapy between December 2017 and December 2021 were analyzed retrospectively. The cutoff value of ALC was set at 1800 cells/μL at the initiation of palbociclib treatment. The clinical benefit rate (CBR) was defined as the rate of complete or partial response or stable disease for at least 6 months. Progression-free survival (PFS) rates were estimated using the Kaplan–Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards regression.ResultsAll of the 202 patients were women, with a median age of 59 years and a performance status (PS) of ≤ 2. The median numbers of lines of chemotherapy and endocrine therapy before palbociclib treatment were 0 (range, 0–9) and 1 (range, 0–7), respectively. Fifty-one patients had liver metastases. Forty-six patients tested negative for progesterone receptor (PgR) expression. The median follow-up time was 9.1 months. The CBR was significantly higher in the ALC-high group than in the ALC-low group (79% vs. 60%; P = 0.018). The median PFS was significantly longer in the ALC-high group than in the ALC-low group (26.8 months vs. 8.4 moths, respectively; P = 0.000013). ALC, age, PS, PgR status, prior chemotherapy, prior endocrine therapy, and liver metastasis were entered into the multivariate analysis. ALC was identified as an independent factor for PFS (P = 0.00085), along with liver metastasis (P = 0.0020), PS (P = 0.026), and prior endocrine therapy (P = 0.019).ConclusionALC can serve as a predictor of palbociclib efficacy in patients with metastatic ER-positive, HER2-negative breast cancer.

Neutrophil-to-lymphocyte ratio at the end of treatment with CDK4/6 inhibitors is an independent prognostic factor for ER-positive HER2-negative advanced breast cancer.

The aim of this study was to elucidate the clinical significance of peripheral blood biomarkers, including absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR), at the end of treatment (EOT) with CDK4/6 inhibitors abemaciclib and palbociclib in patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative advanced breast cancer. We included 67 patients treated with fulvestrant plus abemaciclib or palbociclib. Overall survival (OS) since the EOT with CDK/4/6 inhibitors was compared in relation to the levels of ALC and NLR. The cut-off values of ALC and NLR were set at 1000/μL and 3, respectively. Patients with a high ALC at EOT showed significantly longer OS than those with a low ALC (p = 0.0358). Moreover, patients with a low NLR at EOT showed significantly longer OS than those with a high NLR at EOT (p = 0.0044). Looking at the changes of ALC and NLR between baseline and the EOT, patients with a high ALC both at baseline and at the EOT showed significantly longer OS than others (p = 0.0201). Similarly, patients with a low NLR both at baseline and at the EOT showed significantly longer OS after EOT than others (p = 0.0136). Multivariable analysis revealed that the NLR at EOT (low vs. high) and changes in NLR (low at baseline to low at EOT vs. others) were significant and independent prognostic factors for OS after EOT (p = 0.0337, p = 0.0039, respectively). NLR at EOT with CDK4/6 inhibitors is a significant and independent prognostic marker for patients with ER-positive HER2-negative advanced breast cancer.

Lymphopenia associated with whole-brain radiotherapy and its effects on clinical outcomes of patients with brain metastases

There is increasing awareness of radiotherapy’s potential side effects, such as lymphopenia. Therefore, this study aimed to establish the association between WBRT and the development of lymphopenia in patients with brain metastases undergoing brain radiotherapy (RT), along with evaluating the corresponding clinical outcomes. Including 116 patients with brain metastases undergoing brain radiotherapy, the study collected the absolute lymphocyte counts (ALC) within 2 weeks before brain radiotherapy (pre-radiotherapy, pre-RT), as well as ones at 1 and 2 months after completing RT (post-RT). Univariate and multivariate analyses were performed to identify associations between radiation modality and post-RT ALC. The relationships between post-RT ALC and overall survival were evaluated with Kaplan–Meier analysis and a multivariate Cox regression model. The median ALC definitely decreased at 1 month post-RT, but at 2 months post-RT, gradually rose but not to the pre-RT ALC. The multivariate analysis identified WBRT and lower pre-RT ALC as independent risk factors associated with the decrease in post-RT ALC at 1 month. It also revealed more than 4 brain metastases, G3-4 lymphopenia at 1 month and lower post-RT ALC at 2 months exhibited significantly worse prognosis regardless of the radiation modality. However, there was indeed an independent correlation between radiation modality and the outcome of intracranial progression-free survival (PFS). To approach the feasibility and reasonableness of treatment, clinicians should carefully consider various factors to achieve long-term survival of patients.

Baseline immune state and T-cell clonal kinetics are associated with durable response to CAR-T therapy in large B-cell lymphoma

AbstractEngineered cellular therapy with CD19-targeting chimeric antigen receptor T cells (CAR-Ts) has revolutionized outcomes for patients with relapsed/refractory large B-cell lymphoma (LBCL), but the cellular and molecular features associated with response remain largely unresolved. We analyzed serial peripheral blood samples ranging from the day of apheresis (day –28/baseline) to 28 days after CAR-T infusion from 50 patients with LBCL treated with axicabtagene ciloleucel by integrating single-cell RNA and T-cell receptor sequencing, flow cytometry, and mass cytometry to characterize features associated with response to CAR-T. Pretreatment patient characteristics associated with response included the presence of B cells and increased absolute lymphocyte count to absolute monocyte count ratio (ALC/AMC). Infusion products from responders were enriched for clonally expanded, highly activated CD8+ T cells. We expanded these observations to 99 patients from the ZUMA-1 cohort and identified a subset of patients with elevated baseline B cells, 80% of whom were complete responders. We integrated B-cell proportion ≥0.5% and ALC/AMC ≥1.2 into a 2-factor predictive model and applied this model to the ZUMA-1 cohort. Estimated progression-free survival at 1 year in patients meeting 1 or both criteria was 65% vs 31% for patients meeting neither criterion. Our results suggest that patients’ immunologic state at baseline affects the likelihood of response to CAR-T through both modulation of the T-cell apheresis product composition and promoting a more favorable circulating immune compartment before therapy. These baseline immunologic features, measured readily in the clinical setting before CAR-T, can be applied to predict response to therapy.

Triple burden of hepatitis B, hepatitis Delta viruses, and Plasmodium falciparum to pregnant women

ObjectivesChronic hepatitis B virus (HBV) infection remains a major health problem worldwide. This infection is more severe when combined with hepatitis Delta virus (HDV). Moreover, Plasmodium falciparum (Pf) malaria infection during pregnancy can have severe consequences for the mother and the newborn. Importantly, the manifestation of these three infections has never been described to date. MethodsThus, we conducted a prospective study, between May 27, 2022, and April 15, 2023, and we investigated these three infections in 260 pregnant women aged 24 to 46 years, in Gabon and evaluated the impact on newborns. The sera were used to screen hepatitis B surface antigen (HBsAg) and Pf by determining HBsAg® ALERE rapid diagnostic test and malaria rapid diagnostic test kits. The positive sample was confirmed using MINI VIDAS® for HBV and Lambaréné method for “Pf”. The real-time-polymerase chain reaction assay was used to amplify HBV DNA and HDV RNA on Roche instrument. ResultsOur results showed that the prevalences of HBV and (Pf) infection were 4.23% (n = 11) and 34.62% (n = 90), respectively. Moreover, we found that 3.46 % (n = 9) of pregnant women infected with HBV were coinfected with HDV. The prevalence of triple infection was 1.15% (n = 3). In addition, the leukocytes and lymphocytes absolute count were significantly lower for the triple-infected pregnant women. ConclusionsWe describe for the first time the triple coinfection by HBV, HDV, and Pf, which could induce a great inflammatory reaction and high liver disorder in newborns.

Association between Hematological Parameters and Severity of Covid-19 Infections.

This study aimed to determine the relationships between hematological parameters- hemoglobin, Total Leucocyte Counts (TLC), platelet counts, Absolute Neutrophil Counts (ANC), Absolute Lymphocyte Counts (ALC), Neutrophil Lymphocyte Ratio (NLR), Systemic Immune Inflammatory Index (SII), Neutrophil Monocyte Ratio (NMR), Platelet Lymphocyte Ratio (PLR) and the severity of COVID 19 infections and their use in predicting severity of COVID-19 infections. This was a prospective, observational, single-center study of 573 symptomatic adult inpatients of COVID 19 admitted to our tertiary care center. The above-mentioned hematological parameter levels were noted and compared between the two categories of COVID-19 infection, namely non-severe and severe COVID-19 using logistic regression methods. Their cut-off values were detected using the ROC curve. The median TLC, ANC, NLR, SII, NMR, PLR were notably higher in patients with severe COVID-19 than in those with non-severe COVID-19. Logistic regression analysis showed that NMR (OR=1.029, p=0.006) and ALC (OR=0.999, p=0.002) were statistically significant independent predictors of COVID-19 severity. The hematological parameters mentioned, can be used for predicting severe COVID-19 infections at admission. ALC and NMR levels could be used as hematological markers to predict severity of COVID-19 in adult patients with their cut off values being < 1105 cells/cubic millimeter and > 10.434 respectively.