Baseline Lymphocyte Count Research Articles

Lymphopenia after palliative radiotherapy for vertebral metastases.

Lymphopenia is a well-known side effect of radiotherapy and has been shown to have a negative impact on patient outcomes. However, the extent of lymphopenia caused by palliative radiotherapy and its effect on patient prognosis has not been clarified. The aim of this study was to determine the incidence and severity of lymphopenia after palliative radiotherapy for vertebral metastases and to determine their effects on patients' survival outcomes. We conducted a retrospective analysis for patients who underwent palliative radiotherapy for vertebral metastases and could be followed up for 12weeks. Lymphocyte counts were documented at baseline and throughout the 12-week period following the start of radiotherapy and their medians and interquartile ranges (IQRs) were recorded. Exploratory analyses were performed to identify predictive factors for lymphopenia and its impact on overall survival (OS). A total of 282 cases that met the inclusion criteria were analyzed. The median baseline lymphocyte count was 1.26 × 103/μl (IQR: 0.89-1.72 × 103/μl). Peak lymphopenia occurred at a median of 26days (IQR: 15-45days) with a median nadir of 0.52 × 103/μl (IQR: 0.31-0.81 × 103/μl). Long-term analysis of patients surviving for 1 year showed that lymphopenia persisted at 1 year after radiotherapy. The main irradiation site, radiation field length and pretreatment lymphocyte count were significantly related to grade 3 or higher lymphopenia. Lymphopenia was identified as a significant predictor of OS by multivariate Cox regression analysis. This study demonstrated the incidence of lymphopenia after palliative radiotherapy for vertebral metastases and its effect on patients' OS.

Exploring the prognostic impact of absolute lymphocyte count in patients treated with immune-checkpoint inhibitors

BackgroundThe role of immune checkpoint inhibitors (ICI) expands but affordable and reproducible prognostic biomarkers are needed. We investigated the association between baseline and 3-month absolute lymphocyte count (ALC) and survival for patients on ICI.MethodsA retrospective study investigated patients who received ICI July 2014—August 2019. Survival probabilities were calculated for lymphocyte subsets. Univariate and multivariate analyses were performed to investigate risk factors for lymphopenia.ResultsAmong 179 patients, median age was 62 and 41% were female. The most common diagnoses were melanoma (41%) and lung cancer (40%). Median PFS was 6.5 months. 27% had baseline lymphopenia (ALC < 1 × 109cells/L) and no significant difference in PFS or OS to those with normal ALC. However, 31% had lymphopenia at 3 months and significantly shorter OS than those without (9.8 vs 18.3 months, p < 0.001). Those with baseline lymphopenia who recovered counts at 3 months had no difference in PFS (median NR vs 13.0 months, p = 0.48) or OS (22 vs 18.3 months, p = 0.548) to those never lymphopenic. The strongest risk factor for lymphopenia on multivariable analysis was previous radiation therapy (RT).Conclusions3-month lymphopenia is a negative prognostic marker in cancer patients on ICI. Previous RT is significantly associated with lymphopenia.

The predictive value of systemic inflammatory markers in 902 patients with tunneled hemodialysis catheter

AimThis study aimed to assess the predictive role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and mean platelet volume, on catheter survival in chronic hemodialysis patients, analyzing both infectious and non-infectious complications.MethodsA retrospective analysis encompassed 1279 tunneled catheter insertion procedures involving 902 patients between March 2014 and October 2018. Patients were categorized into two main groups: (i) initial placement and (ii) exchange. The exchange group was further stratified into four subgroups: infection, dysfunction, displacement, and transitioning temporary hemodialysis catheters to long-term ones. Hematologic ratios were calculated from baseline hemogram data, including neutrophil, lymphocyte, monocyte, and platelet counts, while mean platelet volume was derived from the same hemogram.ResultsThe patients in the exchange group displayed significantly higher lymphocyte and monocyte values (p < 0.001), while lower values were noted for neutrophil–lymphocyte ratio and platelet-lymphocyte ratio (p < 0.001). The transition group displayed higher monocyte values and lower mean platelet volume and lymphocyte-monocyte ratio values (p < 0.05). In the infection-related exchange subgroup, higher neutrophil count, mean platelet volume, neutrophil–lymphocyte ratio, and platelet-lymphocyte ratio values were observed compared to other groups (p < 0.05). Cases related to catheter dysfunction exhibited increased lymphocyte-monocyte ratio but lower neutrophil, monocyte, neutrophil–lymphocyte ratio, and platelet-lymphocyte ratio values (p < 0.05).ConclusionThis study highlights the interest of specific inflammatory markers, particularly monocytes, neutrophil–lymphocyte ratio, and platelet-lymphocyte ratio, in the management of tunneled catheters, notably in patients undergoing exchanges. However, cut-off values, essential for constructing management algorithms, are currently lacking, and prospective multicenter studies are needed for further elucidation.Graphical abstract

Early lymphocyte levels and low doses radiation exposure of lung predict lymphopenia in radiotherapy for lung cancer.

Radiation induced lymphopenia (RIL) deteriorate survival and diminishes the benefit of immune checkpoint inhibitors in combined treatment of lung cancer. Given the inconsistent data across various studies on the predictors of RIL, we aim to methodically elucidate these predictors and formulate a practical guide for clinicians. We conducted observational cohort study in four tertiary cancer centers. Patients with non-small cell lung cancer and small cell lung cancer, without lymphopenia grade >1, who underwent standalone radiotherapy (RT) in minimum 15 fractions were eligible. Dose-volume parameters of structures and clinical factors were comprehensively analyzed using various predictors selection methods and statistical models (Linear Regressors, Elastic Net, Bayesian Regressors, Huber Regression, regression based on k-nearest neighbors, Gaussian Process Regressor, Decision Tree Regressor, Random Forest Regressor, eXtreme Gradient Boosting, Automated Machine Learning) and were ranked to predict lymphocytes count nadir (alc_nadir). Two hundred thirty eight patients (stage I-3.4%, II-17.6%, III-75.2%, IV-3.8%) who underwent RT to median dose of 60 Gy were analyzed. Median alc_nadir was 0.68K/mm3. The 60 feature sets were evaluated in 600 models (RMSE 0.27-0.41K/mm³). The most important features were baseline lymphocyte count (alc_1), mean lung_dose, lung v05, lung v10, heart v05 and effective dose to immune cells (edic). In patients with alc_1 ≤ 2.005K/mm3, median alc_nadir predictions were 0.54K/mm3 for lung_v05p > 51.8% and 0.76K/mm3 for lung_v05p ≤ 51.8%. Lymphopenia was rare in patients with alc_1 > 2.005K/mm3. RIL was most severe in patients with low early lymphocyte counts, primarily triggered by low RT doses in the heart and lungs.

Frequency and predictors for early-achieved lupus low disease activity state in systemic lupus erythematosus patients treated with telitacicept or belimumab: A real-life, single-center observational study.

To collect real-world data regarding the attainment of the early-achieved lupus low disease activity state (LLDAS) in systemic lupus erythematosus (SLE) patients receiving telitacicept or belimumab treatment, and identify factors predictive of target achievement. Eighty-seven SLE patients who received telitacicept (N=42) or belimumab (N=45) were retrospectively reviewed in this observational study. Clinical and laboratory data, disease activity assessment, and glucocorticoid dosage were collected for analysis. Achieving LLDAS at least once within 24 weeks post-treatment was considered as early-achieved LLDAS. Multivariate regression was used to assess baseline predictive variables for early-achieved LLDAS. Subgroup analysis and interaction tests were also performed to examine the robustness of the results across different sets of baseline characteristics. Prognostic stratification for early-achieved LLDAS was established based on the identified risk factors. During the 24-week follow-up period, LLDAS was achieved by at least one time in 49.43% (43/87) of the patients, with sustained achievement through week 24 observed in 36 out of these 43 patients (83.27%). Multivariate analysis revealed that early achievement of LLDAS was particularly observed in patients with higher baseline lymphocyte counts [HR=1.79, 95% CI (1.19-2.67), P=0.005]and serum albumin levels [HR=1.06, 95% CI (1.003-1.12), P=0.039]. Conversely, hematological involvement [HR=0.48, 95% CI (0.24-0.93), P=0.031] predicted lower attainment of early-achieved LLDAS. The use of telitacicept was associated with a reduced risk of failing to attain early achievement of LLDAS [HR=2.55, 95% CI (1.36-4.79), P=0.004]. Subgroup analyses and interaction tests showed a stable relationship between the telitacicept use and LLDAS achievement. The results remained consistent across all subgroup analyses. Significant differences (P<0.001) were observed in the Kaplan-Meier estimates for LLDAS among risk groups based on the number of identified risk factors. The achievement of LLDAS is attainable in the management of SLE patients undergoing treatment with telitacicept or belimumab in real-life clinical practice. Baseline lymphocyte counts, serum albumin levels, hematological involvement and the use of telitacicept serve as robust predictors for early-achieved LLDAS, helping to identify patients who are likely to benefit on the treatment.

Early decrease in blood lymphocyte count is associated with poor prognosis in COVID-19 patients: a retrospective cohort study

BackgroundPrevious studies have declared that baseline lymphocyte count is associated with COVID-19-related death. However, whether dynamic lymphocyte change over time affects prognosis in COVID-19 patients is unknown. This study aims to investigate the significance of lymphocyte count during the progression of the disease in COVID-19 patients.MethodsThe retrospective cohort study recruited COVID-19 patients at the First People’s Hospital of Jiangxia District in Wuhan from January 7, 2020, to February 28, 2020. The demographics, medical histories, results of the blood routine test, and patients’ outcomes were collected. We utilized a generalized additive mixed model to compare trends in lymphocyte count over time among survivors and non-survivors, with an adjustment for potential confounders. The statistical analysis used R software and EmpowerStats. Significance was determined at a P-value of less than 0.05 (two-sided).ResultsA total of 532 patients were included in the study. Overall, there were 29/532 in-hospital deaths (5.45%). Lymphocytes declined over time in the non-survivor group and increased in the survivor group in the first 10 days of hospitalization. Within 10 days after admission, lymphocyte count increased in the survivor group and decreased in the non-survivor group. The difference in lymphocyte counts between survivors and non-survivors increased by an average of 0.0732 × 109/L daily. After adjusting for several covariables, the increasing value remained at 0.0731 × 109/L per day.ConclusionIn the early stage, lymphocyte count can dynamically reflect the pathophysiological changes in COVID-19 patients. An early decrease in lymphocyte count is associated with mortality in COVID-19 patients.

Optimizing inhaled corticosteroid use in patients with chronic obstructive pulmonary disease: assessing blood eosinophils, neutrophil-to-lymphocyte ratio, and mortality outcomes in US adults.

Accurate biomarkers for evaluating mortality rates in patients with chronic obstructive pulmonary disease (COPD) remain scarce. This study aimed to explore the relationships between mortality rates in patients with COPD and blood eosinophil counts, neutrophil counts, and lymphocyte counts, along with the neutrophil-to-lymphocyte ratio (NLR). Additionally, we sought to identify the optimal response values for these biomarkers when utilizing inhaled corticosteroids (ICS). Utilizing a nationally representative, multistage cross-sectional design and mortality correlation study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 involving US adults aged 40 years or older with COPD. The primary endpoint was all-cause mortality, with Kaplan-Meier survival curves and restricted cubic splines applied to illustrate the relationship between leukocyte-based inflammatory markers and mortality. The analysis was conducted in 2023. Our analysis included 1,715 COPD participants, representing 6,976,232 non-institutionalized US residents [weighted mean age (SE), 62.09 (0.28) years; range, 40-85 years]. Among the participants, men constituted 50.8% of the population, and the weighted mean follow-up duration was 84.9 months. In the ICS use group, the weighted proportion of participants over 70 years old was significantly higher compared with the non-ICS use group (31.39% vs 25.52%, p < 0.0001). The adjusted hazard ratios for all-cause mortality related to neutrophil counts, lymphocyte counts, and NLR were 1.10 [95% confidence interval (CI), 1.04-1.16, p < 0.001], 0.83 (95% CI, 0.71-0.98; p = 0.03), and 1.10 (95% CI, 1.05-1.15; p < 0.0001), respectively. Optimal ICS response was linked with higher levels of eosinophil count (≥240 cells/μL), neutrophil count (≥3,800 cells/μL), NLR (≥4.79), and lower levels of lymphocyte count (<2,400 cells/μL). Adjusted baseline neutrophil, lymphocyte counts, and NLR serve as independent risk factors for all-cause mortality in patients with COPD. Further, ICS application appears to mitigate mortality risk, particularly when NLR levels reach 4.79 or higher, underlining the importance of ICS in COPD management.

Severe radiation-induced lymphopenia during concurrent chemoradiotherapy for stage III non-small cell lung cancer: external validation of two prediction models.

Severe radiation-induced lymphopenia (RIL) in patients undergoing chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC) is associated with decreased immunotherapy efficacy and survival. At The Christie and MD Anderson Cancer Center (MDACC), prediction models for lymphopenia were developed in lung and esophageal cancer patients, respectively. The aim of this study was to externally validate both models in patients with stage III NSCLC. Patients who underwent concurrent CRT for stage III NSCLC in 2019-2021 were studied. Outcomes were grade ≥3 and grade 4 lymphopenia during CRT. The Christie model predictors for grade ≥3 lymphopenia included age, baseline lymphocyte count, radiotherapy duration, chemotherapy, mean heart and lung doses, and thoracic vertebrae V20Gy. MDACC predictors for grade 4 lymphopenia were age, baseline lymphocyte count, planning target volume (PTV), and BMI. The external performance of both models was assessed. Among 100 patients, 78 patients (78%) developed grade ≥3 lymphopenia, with grade 4 lymphopenia in 17 (17%). For predicting grade ≥3 lymphopenia, the Christie and MDACC models yielded c-statistics of 0.77 and 0.79, respectively. For predicting grade 4 lymphopenia, c-statistics were 0.69 and 0.80, respectively. Calibration for the Christie and MDACC models demonstrated moderate and good agreement, respectively. The PTV-based MDACC prediction model for severe RIL demonstrated superior external performance in NSCLC patients compared to the dosimetry-based Christie model. As such, the MDACC model can aid in identifying patients at high risk for severe lymphopenia. However, to optimize radiotherapy planning, further improvement and external validation of dosimetry-based models is desired.

Teclistamab in Relapsed Refractory Multiple Myeloma: Multi-Institutional Real-World Study

Introduction: Teclistamab is the first BCMA-targeting bispecific antibody (bsAb) that has received FDA approval in RRMM based on the MajesTEC-1 study, which showed a single-agent ORR of 63%. In this report, we present the safety and efficacy of teclistamab since its approval in a real-world multi-institutional cohort. Methods: All consecutive patients with RRMM treated with at least one dose of standard-of-care teclistamab at 5 academic centers in the US were included in this study. Data including patient demographics, disease, and treatment characteristics at the most recent assessment before starting treatment were retrospectively collected. Results: A total of 89 patients were treated across 5 academic institutions. The median age was 68 years (range: 37-89), with 48% (n=43) females. Among the patients, 30% (n=27) were Black, 2.2% (n=2) Asian and 12% (n=11) were other minorities. High-risk cytogenetic profile was observed in 65% (n=49/75) of the patients. About 48% (n=39) of the patients exhibited EMD on PET-CT. Four patients had CNS involvement, 1 had pPCL, and 3 had concomitant AL amyloidosis. Furthermore, 98% (n=87) of the patients had triple-class refractory MM, while 85% (n=76) had penta-refractory MM. The median prior lines of therapy were 6 ( range: 3-13) and 80% (n=71) of patients received a prior ASCT. About 37% (n=33) had received prior BCMA-directed therapy, which included BCMA CAR-T in 17, BCMA BsAb in 5, and Belantamab mafadotin in 11 patients . Table 1 compares this patient cohort with the MajesTEC-1 study population. Grade 1/2 CRS was observed in 48% (n=43) of patients, while 3% (n=3) experienced grade 4 CRS. Grade 1/2 ICANS was noted in 7% (n=6) of patients, grade 3/4 in 4.4% (n=4), and grade 5 in 1 patient. Steroids were utilized in 22% (n=16) of patients, while tocilizumab was administered in 44% (n=32) of patients. Notably, step-up dosing of teclistamab was administered entirely in the outpatient setting in 9% (n=8) of patients. For the remaining, inpatient step-up dosing was administered, and the median hospitalization duration was 10 days. At a median follow-up of 1.35 months (range: 0.16-4.38), the ORR among the evaluable patients was 55%, with rates of ≥ VGPR and PR at 37% (n=28) and 18% (n=13), respectively. The 3-month PFS rate was 54% (95% CI: 43%, 69%), while the 3-month OS rate was 80% (95% CI: 71%, 90%). Multivariate analysis did not reveal any significant associations between disease response and the following factors: number of prior lines of therapy (HR 1.03, 95% CI 0.76-1.42), baseline lymphocyte counts (HR 0.98, 95% CI 0.47-2.02), high-risk cytogenetics (HR 0.38, 95% CI 0.09-1.39) and the presence of extramedullary disease (HR 0.56, 95% CI 0.15-1.93). There was a trend towards worse ORR in patients with prior exposure to BCMA targeting agents, albeit not quite significant (HR 0.28, 95% CI 0.07-1.04, p=0.065). There were 61 infectious events with 50%, 45% and 5% of these being viral, bacterial, and fungal infections, respectively. The most common sources of infections were upper respiratory tract infections/pneumonias (33%), blood borne infections including bacteremia and viremia (27%) and urinary tract infections (11%). The cumulative incidence of any infection at 3 months was 55% and grade 3/4 infections were seen in 55% (n= 54) of cases. There was one grade 5 infection noted in this study due to COVID 19 pneumonia. Primary IVIG and PJP prophylaxis were used in 40% (n=34) and 51% (n=43) of patients, respectively and the use of such was associated with a significant reduction of infectious events (26/51 [51%] of any infectious event for no IVIG use vs 13/34 [38%] for IVIG use, p= 0.015). The results will be updated with longer follow-up at the meeting. Conclusion : In this large real-world, multi-institutional study including a diverse cohort of heavily pretreated patients with triple-class and penta-refractory MM, including approximately 40% with prior BCMA exposure, teclistamab demonstrated a respectable ORR of 55% with ≥ VGPR in 37% of cases. The incidence of Grade 3 or higher infections at 3 months remained high at 56%, however the use of prophylactic measures, including primary IVIG prophylaxis was associated with a significant reduction of all infections and should be strongly considered in patients receiving teclistamab.

Interpretable Deep Learning Identified the Significance of 1 Gy Volume on Lymphopenia after Radiotherapy in Breast Cancer

Lymphopenia is common after radiotherapy (RT) and is known for its significance on poor survival outcomes in patients with breast cancer. Previous work has demonstrated the significance of point dosimetric factors like the volume receiving 5 Gy. Considering the full dosimetric data together, this study aimed to develop and validate predictive models for lymphopenia after RT in breast cancer. Patients with breast cancer treated with radiation therapy in adjuvant setting and with complete dosimetric data were eligible. Combining dose-volume histogram (DVH) dosimetric and clinical factors, dense neural network (DNN) models were developed to predict both the reduction in lymphocyte counts and the graded lymphopenia in breast cancer patients after adjuvant RT. A Shapley additive explanation was applied to explain each feature's directional contributions. The generalization of DNN models was validated in both internal and independent external validation cohorts. P<0.05 was considered to be significant. A total of 928 consecutive patients with invasive breast cancer were eligible for this study. Treatment volumes of nearly all irradiation dose levels of DVH were significant predictors for lymphopenia after RT, including volumes at very low-dose 1 Gy (V1) of all structures considered including the lung, heart and body. DNN models using full DVH dosimetric and clinical factors were built and a simplified model was further established and validated in both internal and external validation cohorts. This simplified DNN AI model, combining full DVH dosimetric parameters of all OARs and five key clinical factors including baseline lymphocyte counts, tumor stage, RT technique, RT fields and RT fractionation, showed a predictive accuracy of 77% and above. This study demonstrated and externally validated the significance of an AI model of combining clinical and full dosimetric data, especially the volume of low dose at as low as 1 Gy of all critical structures on lymphopenia after RT in patients with breast cancer. The significance of V1 deserves special attention, as modern arc RT technology often has relatively high value of this parameter. Further study warranted for breast cancer RT plan optimization.

Which factors are predicting the mortality in patients with COVID-19 in the intensive care unit?

Aims: COVID-19 infection is a global health problem; clinical and laboratory parameters have been developed to predict this disease-related mortality/morbidity. Some of these parameters are clinical parameters, while some are laboratory parameters. This study aims to determine whether Acute Physiology and Chronic Health Evaluation (APACHE) II, Glasgow Coma Scale (GCS), age, presence of comorbidity, and absolute lymphocyte count effectively predict mortality in patients admitted to intensive care unit (ICU) due to COVID-19.&#x0D; Methods: We have included 108 PCR-positive COVID-19 patients admitted to the ICU between 1 October and 31 November 2020 in our research. Demographic characteristics of all patients, APACHE II values within the first 24 hours of admission to ICU, the GCS, the presence of comorbidity, lymphocyte count during ICU admission, duration of ICU stay, and the mortality rates were recorded.&#x0D; Results: The average age of 108 individuals evaluated in the study was 67±13.61 years, and 56.5% of the patient group consisted of the geriatric age range. Seventy (64.8%) of the patients were female, eighty-nine (82.4%) patients had at least one comorbidity. In the multivariate analysis, it was determined that lymphocyte value, APACHE II score, and the presence of any comorbidity are independent prognostic factors for mortality when accepted to ICU.&#x0D; Conclusion: In our study, we have determined that age, APACHE II value, presence of comorbidity, and baseline lymphocyte counts are independent predictors of mortality.

Simple parameters from complete blood count predict lymphopenia, adverse effects and efficacy in people with MS treated with dimethyl fumarate.

Dimethyl fumarate (DMF) is a first-line oral therapy for relapsing-remitting multiple sclerosis (RRMS). This retrospective study aims to determine the utility of routine complete blood counts (CBC) in predicting lymphopenia, adverse effects and efficacy in a real-world clinical setting. The Calgary Multiple Sclerosis (MS) Clinic manages over 1800 people with MS on disease-modifying therapies (DMT). Data of patients with relapsing-remitting MS (pwMS) who initiated DMF between July 1, 2013 and December 31, 2014 were included. Patients were followed for one year. DMT use is carefully monitored and pwMS need a screening CBC and have regular CBCs done at follow-up. Demographic, clinical, MRI and relapse information are collected prospectively in a clinic database. We analyzed CBCs at baseline and month 3. We identified 139 pwMS in the study period who started DMF. Median follow-up time on-drug was 12 (0.16-12) months. In our study, 15.8% of pwMS developed lymphopenia grade 2 or higher. Baseline lymphocyte counts and older age were significant predictors of lymphopenia. Higher baseline eosinophil counts predicted flushing/gastrointestinal adverse effects, and higher baseline monocyte counts were predictive of breakthrough disease activity. Neutrophil and platelet to lymphocyte ratios, markers that have been associated with overall mortality in the general population, were increased at month 3. Routinely obtained CBCs during the screening and monitoring of people with MS starting DMF offer clinically useful information and generate interesting hypotheses. Age and baseline lymphocyte counts are reinforced as clinically useful predictors of lymphopenia. Our novel findings that baseline eosinophil and monocyte counts could offer insights into usual adverse effects and efficacy, respectively, should be further investigated as a potentially new set of biomarkers.

The Predictive Values of White Blood Cell Indices (Lymphocyte and Eosinophilic Granulocyte) for Heart Failure in Acute Coronary Syndrome Patients Following Percutaneous Coronary Intervention: A Prospective Cohort Study.

White blood cell (WBC) indices are strongly associated with cardiovascular disease, but data on the prognostic values of these parameters in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) are sparse. The current study aimed to investigate the relationship between baseline WBC indices levels and the incidence of heart failure (HF) in ACS patients after PCI and explore the predictive values over a 2-year follow-up period. A total of 416 consecutive ACS patients treated with PCI were enrolled and received a median of 27.7 months follow-up. Univariate and multivariate Cox regression analyses and the receiver operating characteristic (ROC) curves were performed. Baseline lymphocyte (LYMPH) count, eosinophil (EO) count and eosinophil percentage (EO %) were higher in patients who experienced HF over a 2-year follow-up. In multivariate Cox proportional hazards analysis, LYMPH count, EO count and EO % were independently associated with the occurrence of HF (hazard ratio [HR] = 12.876, P = 0.025; HR = 16.625, P = 0.004; HR = 1.196, P = 0.031, respectively). The area under the ROC curve of baseline EO count predicting the occurrence of HF in ACS patients following PCI was 0.625 (P = 0.037). For patients aged 60 years and above, who had PCI or history of coronary artery bypass grafting, the higher EO count, the higher the risk of HF. Elevated baseline LYMPH count, EO count and EO % were independently associated with the incidence of HF in ACS patients following PCI, suggesting that WBC indices might be available, simple, and cost-efficient biomarkers with predictive value, especially for patients aged more than 60 years.

Effectiveness and safety profile of cladribine in an Italian real-life cohort of relapsing–remitting multiple sclerosis patients: a monocentric longitudinal observational study

IntroductionCladribine is approved for the treatment of active relapsing MS (RRMS), but its positioning in MS therapeutic scenario still needs to be fully elucidated.MethodsThis is a monocentric, observational, real-world study on RRMS patients treated with cladribine. Relapses, magnetic resonance imaging (MRI) activity, disability worsening, and loss of no-evidence-of-disease-activity-3 (NEDA-3) status were assessed as outcomes. White blood cell, lymphocyte counts and side effects were also evaluated. Patients were analyzed overall and in subgroups according to the last treatment before cladribine. The relationship between baseline characteristics and outcomes was tested to identify predictors of response.ResultsAmong the 114 patients included, 74.9% were NEDA-3 at 24 months. We observed a reduction of relapses and MRI activity, along with a stabilization of disability. A higher number of gadolinium-enhancing lesions at baseline was the only risk factor for loss of NEDA-3 during follow-up. Cladribine was more efficacious in switchers from first-line therapies or naïves. Grade I lymphopenia was more frequent at month 3 and 15. No grade IV lymphopenia cases were observed. Independent predictors of grade III lymphopenia were a lower baseline lymphocyte count and a higher number of previous treatments. Sixty-two patients presented at least one side effect and globally 111 adverse events were recorded, none of them was serious.ConclusionsOur study confirms previous data on cladribine effectiveness and safety. Cladribine is more effective when placed early in the treatment algorithm. Real-world data on larger populations with longer follow-up are needed to confirm our findings.

Lymphocytopenia and survival after whole-brain radiotherapy in patients with small-cell lung cancer.

To investigate whether whole-brain radiotherapy (WBRT) decreases lymphocyte counts and evaluate the impact of treatment-related lymphopenia on survival in patients with brain metastasis. Medical records from 60 small-cell lung cancer patients treated with WBRT from January 2010 to December 2018 were included in the study. Total lymphocyte count (TLC) was obtained pre and post treatment (within 1 month). We performed linear and logistic regression analyses to identify predictors of lymphopenia. The association between lymphopenia and survival was analyzed using Cox regression analysis. Thirty-nine patients (65%) developed treatment-related lymphopenia. The median TLC decrease was -374 cells/μL (interquartile range -50 to -722, p < 0.001). Baseline lymphocyte count was a significant predictor of TLC difference and percentage change in TLC. Logistic regression analysis found male sex (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.00-0.79, p = 0.033) and higher baseline lymphocyte count (OR 0.91, 95% CI 0.82-0.99, p = 0.005) were associated with a lower risk of developing ≥grade 2 treatment-related lymphopenia. Cox regression analysis showed that age at brain metastasis (hazard ratio [HR] 1.03, 95% CI 1.01-1.05, p = 0.013), ≥grade 2 treatment-related lymphopenia, and percentage change in TLC (per 10%, HR 0.94, 95% CI 0.89-0.99, p = 0.032) were prognostic factors of survival. WBRT decreases TLC and the magnitude of treatment-related lymphopenia is an independent predictor of survival in small-cell lung cancer patients.

Reduced radiation exposure to circulating blood cells in proton therapy compared with X-ray therapy in locally advanced lung cancer: Computational simulation based on circulating blood cells.

We estimated the dose of circulating blood cells (CBCs) in patients with locally advanced non-small cell lung cancer for predicting severe radiation-induced lymphopenia (SRIL) and compared pencil-beam scanning proton therapy (PBSPT) and intensity-modulated (photon) radiotherapy (IMRT). After reviewing 325 patients who received definitive chemoradiotherapy with PBSPT (n = 37) or IMRT (n = 164). SRIL was diagnosed when two or more events of an absolute lymphocyte count < 200 µL occurred during the treatment course. Dose information for the heart and lungs was utilized for the time-dependent computational dose calculation of CBCs. The dose distribution of CBCs was significantly lesser in the PBSPT group than that in the IMRT group. Overall, 75 (37.3%) patients experienced SRIL during the treatment course; 72 and 3 patients were treated with IMRT and PBSPT, respectively. SRIL was associated with poor progression-free and overall survival outcomes. Upon incorporating the dose information of CBCs for predicting SRIL, CBC D90% > 2.6 GyE was associated with the development of SRIL with the baseline lymphocyte count and target volume. Furthermore, PBSPT significantly reduced the dose of CBC D90% (odds ratio = 0.11; p = 0.004) compared with IMRT. The results of this study demonstrate the significance of the dose distribution of CBCs in predicting SRIL. Furthermore, reducing the dose of CBCs after PBSPT minimized the risk of SRIL. Lymphocyte-sparing radiotherapy in PBSPT could improve outcomes, particularly in the setting of maintenance immunotherapy.

Peripheral blood lymphocytes predict clinical outcomes in hormone receptor-positive HER2-negative advanced breast cancer patients treated with CDK4/6 inhibitors.

Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) combined with Endocrine Therapy (ET) are the standard treatment for patients with Hormone Receptor-positive/HER2-negative advanced breast cancer (HR+/HER2- aBC). While CDK4/6i are known to reduce several peripheral blood cells, such as neutrophils, lymphocytes and platelets, the impact of these modulations on clinical outcomes is unknown. A multicenter, retrospective-prospective Italian study. We investigated the association between baseline peripheral blood cells, or their early modifications (i.e. 2 weeks after treatment initiation), and the progression-free survival (PFS) of HR+/HER2- aBC patients treated with ETs plus CDK4/6i. Random Forest models were used to select covariates associated with patient PFS among a large list of patient- and tumor-related variables. We evaluated 638 HR+/HER2- aBC patients treated with ET plus CDK4/6i at six Italian Institutions between January 2017 and May 2021. High baseline lymphocyte counts were independently associated with longer PFS [median PFS (mPFS) 20.1 versus 13.2 months in high versus low lymphocyte patients, respectively; adjusted Hazard Ratio (aHR): 0.78; 95% confidence interval (CI): 0.66-0.92; p = 0.0144]. Moreover, patients experiencing a lower early reduction of lymphocyte counts had significantly longer PFS when compared to patients undergoing higher lymphocyte decrease (mPFS 18.1 versus 14.5 months; aHR: 0.82; 95% CI: 0.73-0.93; p = 0.0037). Patients with high baseline lymphocytes and undergoing a lower reduction, or even an increase, of lymphocyte counts during CDK4/6i therapy experienced the longest PFS, while patients with lower baseline lymphocytes and undergoing a higher decrease of lymphocytes had the lowest PFS (mPFS 21.4 versus 11 months, respectively). Baseline and on-treatment modifications of peripheral blood lymphocytes have independent prognostic value in HR+/HER2- aBC patients. This study supports the implementation of clinical strategies to boost antitumor immunity in patients with HR+/HER2- aBC treated with ETs plus CDK4/6i.

Sarcopenia using pectoralis muscle area and lymphocyte-to-monocyte ratio (LMR) are independent prognostic factors in patients for nonmetastatic breast cancer.

Sarcopenia is defined as loss of skeletal muscle mass and strength. This can lead to adverse clinical outcomes in patients with advanced cancer. The lymphocyte-to-monocyte ratio (LMR), a converted inflammatory response, is associated with poor prognosis in patients with malignancies. Herein, we examined the prognostic influence of sarcopenia status assessed by pectoralis muscle area (PMA), inflammatory status calculated by LMR, and its association with disease-free survival (DFS) in a cohort of women diagnosed with nonmetastatic breast cancer. A total of 293 patients with nonmetastatic breast cancer who underwent primary mass resection and radiotherapy between January 2011 and December 2017 were enrolled. The cross-sectional area of the muscle (cm2) at PMA was measured using computed tomography before radiation therapy. Baseline monocyte and lymphocyte counts were obtained from the complete blood count to calculate the LMR. Most of the patients (248/293, 84.6%) underwent breast conservation surgery. Lymph node involvement at diagnosis (hazard ratio [HR], 5.08; P < .001), low LMR (HR, 2.79; P = .007), and low PMA (HR, 3.80; P < .001) were independent poor prognostic factors in multivariate analysis. The mean DFS of sarcopenic and nonsarcopenic patients was 89.8 months and 118.8 months, respectively (P < .001). Sarcopenic patients with low LMR showed the worst outcomes, whereas nonsarcopenic patients with high LMR showed the best outcomes. Low PMA and low LMR were independent poor prognostic factors for DFS in patients with nonmetastatic breast cancer.

Blood Neutrophil Count and Neutrophil-to-Lymphocyte Ratio for Prediction of Disease Progression and Mortality in Two Independent Systemic Sclerosis Cohorts.

To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease severity and mortality in systemic sclerosis (SSc). Neutrophil and lymphocyte counts were prospectively measured in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) and the Scleroderma Lung Study II (SLS II). Forced vital capacity percent predicted (FVC%) and modified Rodnan skin thickness score (MRSS) were used as surrogate measures for disease severity. Longitudinal analyses were performed using generalized linear mixed models. Cox proportional hazards models evaluated the predictive significance of these cell counts for mortality. Of the 447 SSc patients in the GENISOS cohort at the time of analysis, 377 (84.3%) had available baseline blood neutrophil and lymphocyte counts. Higher baseline neutrophil count and NLR predicted lower serially obtained FVC% (b= -4.74, P=0.009 and b=-2.68, P=0.028, respectively) and higher serially obtained MRSS (b=4.07, P < 0.001 and b=2.32, P < 0.001, respectively). Longitudinal neutrophil and NLR measurements also significantly correlated with lower concurrently obtained FVC% measurements and higher concurrently obtained MRSS. Baseline neutrophil count and NLR predicted increased risk of long-term mortality, even after adjustment for baseline demographic and clinical factors (hazard ratio [HR] 1.42, P=0.02 and HR 1.48, P < 0.001, respectively). The predictive significance of higher baseline neutrophil count and NLR for declining FVC% and increased long-term mortality was confirmed in the SLS II. Higher blood neutrophil count and NLR are predictive of more severe disease course and increased mortality, indicating that these easily obtainable laboratory studies might be a reflection of pathologic immune processes in SSc.

Do Laboratory Biomarkers Predict Survival In Severe Covid-19? A Cross-Sectional Study.

This study aims to compare lymphocyte count, C-reactive protein (CRP), ferritin, Lactate Dehydrogenase (LDH) and D-dimer among survivors and non-survivors of severe COVID-19. This retrospective cross-sectional analytical study included 69 patients for whom a record of the biomarkers and survival status was available. Baseline and peak values were selected for serum CRP, ferritin, LDH and D-Dimer. Baseline and trough lymphocyte counts were selected. Data were analyzed using SPSS version 21. Mean and standard deviation were used to compare the biomarkers with paired t-test. p-value <0.05 was taken as significant. The mean age of the study population was 55.5±9.1 years and 50 (72.5%) were male. Among survivors, the increase in CRP level was not significant (from 15.80±9.8 mg/dl to 17.87±8.4 mg/dl, p=0.45) while it was significant in non-survivors (from 16.68±10.90 mg/dl to 20.77±12.69 mg/dl, p=0.04). There was no significant rise in LDH levels in survivors (from 829.59±499 U/L to 1018.6±468 U/L, p=0.20) while it increased significantly in non-survivors (from 816.2±443.08 U/L to 1056.61±480.54 U/L, p=0.003). The decrease in lymphocyte count and increase in D-Dimers in both the groups was significant (p=0.001). There was no significant elevation in ferritin in both the groups (p>0.05). In severe COVID-19 patients, serum CRP and LDH can be used for risk stratification and predicting survival. Lymphopenia, increase in serum ferritin and D-dimers may not predict survival.