Low Absolute Lymphocyte Count Research Articles

Low Absolute Lymphocyte Count Correlates with Lymph Node Metastases and Worse Survival of Patients with Gastric Cancer.

Several studies have found that the absolute lymphocyte (ALC) or neutrophil count predicts the survival of patients with solid tumors, and that the neutrophil-to-lymphocyte ratio and the prognostic nutritional index are useful markers of gastric cancer prognosis. However, it remains unclear whether the ALC is prognostic of lymph node (LN) metastasis in patients with gastric cancer. In this study, we aimed to explore the impact of ALC on prognosis and distinctive clinical characteristics in patients with gastric cancer. The medical records of patients with gastric adenocarcinomas who underwent radical gastrectomy with curative intent at Seoul St. Mary's Hospital and Yeouido St. Mary's Hospital between January 2010 and December 2017 were reviewed. Of these, 4149 patients for whom preoperative white blood cell, neutrophil, and lymphocyte counts were available were enrolled. In all 4149 patients, ALC gradually decreased as the pN stage increased. Those with an ALC of less than 1360 cells/μL were defined as a low-ALC group, and advanced cT and cN stages were the strongest risk factors for LN metastasis in both univariate and multivariate analyses; undifferentiated tumor histology and a low ALC were also significant risk factors. Patients of all stages in the ALC-low group exhibited poorer prognoses. The ALC-low group also exhibited a higher recurrence rate in a greater proportion of LNs. In patients with gastric cancer, as the preoperative ALC decreases, the incidence of LN metastasis increases. A low ALC is associated with a high recurrence rate, particularly in LNs.

Clinical Profile and Outcome of Severe Acute Respiratory Illness (SARI) in Children Amidst the COVID-19 Pandemic.

Beginning in December 2019, COVID-19 rapidly emerged as a global pandemic. Though its severity in children was reported to be less than that in adults, data on its epidemiology in relation to severe acute respiratory illness (SARI) caused by other microbes needed to be generated. This study compares theclinical profile and outcome of children hospitalized with COVID-19-positive and negative SARI. This is a prospective observational analytical study involving children 1 month to 18 years old, hospitalized with COVID-19-positive and negative SARI during the pandemic. All eligible patients were enrolled after obtaining informed parental consent. Their clinical manifestations, investigations, and outcomes were documented on a predesigned case record form. A nasopharyngeal swab sample for COVID-19 reverse transcription polymerase chain reaction was sent, and results were noted. From May 2020 to July 2021, 267 children were hospitalized with a diagnosis of SARI. Out of these, 146 (54.7%) were boys and 78.7% were under five years of age. Other presentations included fever and cough, breathlessness, nausea, vomiting, diarrhea, rash, seizures, and altered sensorium. Twenty-eight patients (10.5%) tested positive for COVID-19. COVID-19 patients were similar in terms of demographic characteristics and presenting symptoms to non-COVID-19 patients but had a lower absolute lymphocyte count (p = 0.019) and higher serum alanine transaminase levels (p = 0.013). Acute respiratory distress syndrome (OR, 4.3; 95% CI, 1.8-10.0),shock (OR, 3.9; 95% CI, 1.9-7.9), and need for intensive care unit admission (OR, 9.9; 95% CI, 6.9-14) were more common in COVID-19 SARI patients. Death occurred in 18% of COVID-19 and 9% of non-COVID-19 patients (p = 0.07). SARI nonsurvivors had significantly lower blood pH and platelet counts than survivors. Comparison of COVID-19-positive and negative SARI patients showed subtle differences between the two groups, with COVID-19-positive children having an increased severity of illness. Also, laboratory evidence of multiorgan dysfunction at admission was associated with higher mortality.

Abstract PO2-15-03: Platelet-to-lymphocyte ratio in patients with metastatic breast cancer treated with eribulin

Abstract Eribulin is widely used to treat metastatic breast cancer (BC). Higher neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) are associated with higher mortality in several cancer types. However, the association between BC prognosis and peripheral immune status remains controversial. We quantified the relative effects of NLR and PLR on survival in patients with recurrent/stage IV BC and evaluated their clinical prognostic value. This retrospective study included 156 patients with recurrent/stage IV BC who received eribulin monotherapy at Saitama Medical University International Medical Center. We examined clinicopathological features (peripheral blood findings and biochemical liver and kidney function test results) and conducted univariate and multivariate analyses of the overall survival (OS). The 156 eribulin-treated patients had a median follow-up duration of 18.3 months. Before eribulin treatment, patients with absolute lymphocyte counts (ALC) >1500/uL, NLRs < 3.0, and PLRs < 150 had significantly longer OS than those with lower ALCs, and higher NLR and PLRs (median OS, 25.5 vs. 15.5 months; p< 0.01; 20.3 vs. 13.6 months, P< 0.01; and 29.2 vs. 14.8 months; P< 0.001, respectively). Patients with anemia (hemoglobin < 10 g/dL) or liver dysfunction (albumin-bilirubin grade 2/3) had significantly shorter OS than those without (P< 0.001, respectively). Multivariate analysis revealed low albumin-bilirubin grade (P< 0.001), high hemoglobin (P< 0.01), and low PLR (P< 0.05) as independent factors of longer OS after eribulin administration. Low PLR, anemia, and liver dysfunction might be factors associated with prolonged OS in patients with recurrent/stage IV BC on eribulin therapy, which could be clinically useful, as their evaluation requires neither new equipment nor invasive testing. Citation Format: Hiroko Shimada, Kazuo Matsuura, Shunsuke Kohyama, Aya Asano, Masahiro Ohara, Hiroshi Ishiguro, Akihiko Osaki, Toshiaki Saeki. Platelet-to-lymphocyte ratio in patients with metastatic breast cancer treated with eribulin [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-15-03.

Absolute lymphocyte count and neutrophil-to-lymphocyte ratio as predictors of CDK 4/6 inhibitor efficacy in advanced breast cancer.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the standard agents for treating patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (ER + HER2 - ABC). However, markers predicting the outcomes of CDK4/6i treatment have yet to be identified. This study was a single-center retrospective cohort study. We retrospectively evaluated 101 patients with ER + HER2 - ABC receiving CDK4/6i in combination with endocrine therapy at Fukuyama City Hospital between November 2017 and July 2021. We investigated the clinical outcomes and the safety of CDK4/6i treatment, and the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) as predictive markers for CDK4/6i. We defined the cut-off values as 1000/μL for ALC and 3 for NLR, and divided into "low" and "high" groups, respectively. We evaluated 43 and 58 patients who received abemaciclib and palbociclib, respectively. Patients with high ALC and low NLR had significantly longer overall survival than those with low ALC and high NLR (high vs. low; ALC: HR 0.29; 95% CI 0.12-0.70; NLR: HR 2.94; 95% CI 1.21-7.13). There was no significant difference in efficacy between abemaciclib and palbociclib and both had good safety profiles. We demonstrated that ALC and NLR might predict the outcomes of CDK4/6i treatment in patients with ER + HER2 - ABC.

Treatment response of advanced HNSCC towards immune checkpoint inhibition is associated with an activated effector memory T cell phenotype.

Locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis. The introduction of PD-1 inhibitors has led to a significant improvement in survival, but only a subpopulation of patients responds to therapy. Current biomarkers cannot reliably identify these patients. The identification of biomarkers for the prediction and monitoring of immunotherapy is therefore of great importance. In this study, we characterized lymphocyte subsets in the peripheral blood of HNSCC patients under PD-1 inhibition. Patients with primary response (n=11) to PD-1 inhibition showed an increase of the CD3+ effector memory (CD3/EM) population and an elevated expression of the activation marker CD69 in CD3+ T cells, particularly in the CD3/EM subpopulation at 3 months when treatment response was assessed. In contrast, patients with primary treatment failure and progressive disease (n=9) despite PD-1 inhibition had lower absolute lymphocyte counts and an increased expression of CTLA-4 in CD3+ T cells at the time of treatment failure compared with baseline, particularly in CD4+ and CD8+ effector memory populations. Our results demonstrate that HNSCC patients' response to immune checkpoint inhibition shows a distinct immune signature in peripheral blood, which could help identify refractory patients earlier. Furthermore, strategies to overcome primary therapy failure by inducing a beneficial T cell phenotype or adding alternative immune checkpoint inhibitors could improve response rates and survival of HNSCC patients.

Machine learning-based prediction of in-hospital mortality for critically ill patients with sepsis-associated acute kidney injury

Objectives This study aims to develop and validate a prediction model in-hospital mortality in critically ill patients with sepsis-associated acute kidney injury (SA-AKI) based on machine learning algorithms. Methods Patients who met the criteria for inclusion were identified in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and divided according to the validation (n = 2440) and development (n = 9756, 80%) queues. Ensemble stepwise feature selection method was used to screen for effective features. The prediction models of short-term mortality were developed by seven machine learning algorithms. Ten-fold cross-validation was used to verify the performance of the algorithm in the development queue. The area under the receiver operating characteristic curve (ROC-AUC) was used to evaluate the differentiation accuracy and performance of the prediction model in the validation queue. The best-performing model was interpreted by Shapley additive explanations (SHAP). Results A total of 12,196 patients were enrolled in this study. Eleven variables were finally chosen to develop the prediction model. The AUC of the random forest (RF) model was the highest value both in the Ten-fold cross-validation and evaluation (AUC: 0.798, 95% CI: 0.774–0.821). According to the SHAP plots, old age, low Glasgow Coma Scale (GCS) score, high AKI stage, reduced urine output, high Simplified Acute Physiology Score (SAPS II), high respiratory rate, low temperature, low absolute lymphocyte count, high creatinine level, dysnatremia, and low body mass index (BMI) increased the risk of poor prognosis. Conclusions The RF model developed in this study is a good predictor of in-hospital mortality for patients with SA-AKI in the intensive care unit (ICU), which may have potential applications in mortality prediction.

COVID-19 in Pediatric Patients With Acute Lymphoblastic Leukemia or Lymphoma

COVID-19 in pediatric patients with acute lymphoblastic leukemia or lymphoma (ALL/LLy) has not been described in detail and may affect chemotherapy administration and long-term outcomes. To describe the clinical presentation of COVID-19 and chemotherapy modifications in pediatric patients with ALL/LLy. This is a retrospective case series of patients at St Jude Children's Research Hospital and its affiliate sites with newly diagnosed ALL/LLy who were treated on the Total XVII protocol (NCT03117751) between March 30, 2020, and June 20, 2022. Participants included patients aged 1 to 18 years who were receiving protocol chemotherapy. Acute symptoms and chemotherapy modifications were evaluated for 60 days after the COVID-19 diagnosis, and viral clearance, adverse events, and second SARS-CoV-2 infections were followed up during the 27-month study period. SARS-CoV-2; all patients were screened at least weekly and at symptom onset and/or after known exposure to SARS-CoV-2. Description of the spectrum of COVID-19 illness and chemotherapy modifications. Of 308 pediatric patients, 110 (36%) developed COVID-19 at a median age of 8.2 (IQR, 5.3-14.5) years. Sixty-eight patients (62%) were male. Most patients were in the continuation/maintenance phase of chemotherapy (101 [92%]). Severe disease was rare (7 [6%]) but was associated with older age, higher white blood cell counts at ALL/LLy diagnosis, lower absolute lymphocyte counts at COVID-19 diagnosis, abnormal chest imaging findings, and SARS-CoV-2 reinfection. Rare but serious thrombotic events included pulmonary embolism and cerebral venous sinus thrombosis (n = 1 for each). No multisystem inflammatory syndrome in children or death was seen. SARS-CoV-2 reinfection occurred in 11 patients (10%) and was associated with older age and with receiving standard or high-risk vs low-risk ALL/LLy therapy. Chemotherapy interruptions occurred in 96 patients (87%) and were longer for patients with severe disease, SARS-CoV-2 reinfection, and/or a COVID-19 diagnosis during the pre-Omicron variant period vs the post-Omicron period (after December 27, 2021). In this case series of COVID-19 in pediatric patients with ALL/LLy, severe COVID-19 was rare, but chemotherapy administration was affected in most patients. Long-term studies are needed to establish the outcomes of COVID-19 in this population.

Human herpesvirus type 6 reactivation after haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide and antithymocyte globulin: risk factors and clinical impact.

Human herpesvirus type 6 (HHV6) reactivation after haploidentical hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PT-Cy) has been scarcely studied, especially when antithymocyte globulin (ATG) is added to the graft-versus-host disease (GvHD) prophylaxis. We conducted a retrospective cohort study in 100 consecutive patients receiving haploidentical HCT with PT-Cy. We systematically monitored HHV6 DNA loads in blood samples on a weekly basis using quantitative PCR until day +100. The 100-day cumulative incidence of HHV6 reactivation was 54%. Clinically significant HHV6 infections were rare (7%), associated with higher HHV6 DNA loads, and had favorable outcomes after antiviral therapy. The main risk factor for HHV6 reactivation was a low absolute lymphocyte count (ALC) \< 290/µL on day +30 (68% versus 40%, p = 0.003). Adding ATG to PT-Cy did not increase the incidence of HHV6 reactivation (52% with ATG versus 79% without ATG, p = 0.12). Patients experiencing HHV6 reactivation demonstrated delayed platelet recovery (HR 1.81, 95% CI 1.07-3.05, p = 0.026), higher risk of acute grade II-IV GvHD (39% versus 9%, p \< 0.001) but similar overall survival and non-relapse mortality to the other patients. In conclusion, our findings endorse the safety of combining ATG and PT-Cy in terms of the risk of HHV6 reactivation and infection in patients undergoing haploidentical HCT. Patients with a low ALC on day +30 face a higher risk of HHV6 reactivation and may require careful monitoring.

Clinical characteristics and outcomes among critically ill patients with cancer and COVID-19-related acute respiratory failure

BackgroundCoronavirus disease 2019 (COVID-19) has affected individuals worldwide, and patients with cancer are particularly vulnerable to COVID-19-related severe illness, respiratory failure, and mortality. The relationship between COVID-19 and cancer remains a critical concern, and a comprehensive investigation of the factors affecting survival among patients with cancer who develop COVID-19-related respiratory failure is warranted. We aim to compare the characteristics and outcomes of COVID-19-related acute respiratory failure in patients with and without underlying cancer, while analyzing factors affecting in-hospital survival among cancer patients.MethodsWe conducted a retrospective observational study at Taipei Veterans General Hospital in Taiwan from May to September 2022, a period during which the omicron variant of the severe acute respiratory syndrome coronavirus 2 was circulating. Eligible patients had COVID-19 and acute respiratory failure. Clinical data, demographic information, disease severity markers, treatment details, and outcomes were collected and analyzed.ResultsOf the 215 enrolled critically ill patients with COVID-19, 65 had cancer. The patients with cancer were younger and had lower absolute lymphocyte counts, higher ferritin and lactate dehydrogenase (LDH) concentrations, and increased vasopressor use compared with those without cancer. The patients with cancer also received more COVID-19 specific treatments but had higher in-hospital mortality rate (61.5% vs 36%, P = 0.002) and longer viral shedding (13 vs 10 days, P = 0.007) than those without cancer did. Smoking [odds ratio (OR): 5.804, 95% confidence interval (CI): 1.847–39.746], elevated LDH (OR: 1.004, 95% CI: 1.001–1.012), vasopressor use (OR: 5.437, 95% CI: 1.202–24.593), and new renal replacement therapy (OR: 3.523, 95% CI: 1.203–61.108) were independent predictors of in-hospital mortality among patients with cancer and respiratory failure.ConclusionCritically ill patients with cancer experiencing COVID-19-related acute respiratory failure present unique clinical features and worse clinical outcomes compared with those without cancer. Smoking, elevated LDH, vasopressor use, and new renal replacement therapy were risk factors for in-hospital mortality in these patients.

Gestational age-specific hematological features in preterm infants with necrotizing enterocolitis.

This study aimed to investigate gestational age-specific hematological features in preterm infants with necrotizing enterocolitis (NEC) and identify predictive hematological biomarkers for surgical NEC. We conducted a retrospective study comparing gestational age (GA)-specific clinical data between medical NEC (m-NEC) and surgical NEC (s-NEC) subgroups, stratified by GA as <28 weeks, 28 ≤ GA < 32 weeks, and 32 ≤ GA < 37 weeks. Multivariate logistic analysis and receiver operating characteristic curve were used to identify the independent predictors of s-NEC. In comparison to m-NEC at NEC onset, s-NEC infants exhibited the following findings: In GA < 28 weeks, s-NEC infants had lower platelet counts. In 28 ≤ GA < 32 weeks, lower absolute lymphocyte counts, and significant percent drop in platelets, lymphocytes, and monocytes were observed. In 32 ≤ GA < 37 weeks, lower absolute lymphocyte counts and significant percent drop in lymphocytes were found. Independent predictors were able to distinguish s-NEC from m-NEC. The area under the curve (AUC) for platelet counts in GA < 28 weeks was 0.880, while C-reactive protein in 28 ≤ GA < 32 weeks had an AUC of 0.889. The AUC for lymphocyte counts in 32 ≤ GA < 37 weeks was 0.892. This study identified hematological abnormalities in the development of NEC based on gestational age. Independent predictors may help clinicians distinguish surgical NEC from medical NEC. Necrotizing enterocolitis (NEC) patients with different gestational ages (GA) exhibit different hematological features and independent predictors of surgical NEC differ among different GAs. Our research made the current studies about peripheral hematological features with NEC more complete by analyzing peripheral data collected within 24 h of birth, at day 5-7, day 3-4, day 1-2 before NEC onset, at the time of NEC onset, day 1, day 2, day 3, day 4-5, day 6-7 after NEC onset. Our study is helpful to clinicians in developing a more detailed diagnostic strategy based on GA for the early identification of surgical NEC.

Early absolute lymphocyte count was associated with one-year mortality in critically ill surgical patients: A propensity score-matching and weighting study.

Absolute lymphocyte count (ALC) is a crucial indicator of immunity in critical illness, but studies focusing on long-term outcomes in critically ill patients, particularly surgical patients, are still lacking. We sought to explore the association between week-one ALC and long-term mortality in critically ill surgical patients. We used the 2015-2020 critical care database of Taichung Veterans General Hospital (TCVGH), a referral hospital in central Taiwan, and the primary outcome was one-year all-cause mortality. We assessed the association between ALC and long-term mortality by measuring hazard ratios (HRs) with 95% confidence intervals (CIs). Furthermore, we used propensity score-matching and -weighting analyses, consisting of propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and covariate balancing propensity score (CBPS), to validate the association. A total of 8052 patients were enrolled, with their one-year mortality being 24.2%. Cox regression showed that low ALC was independently associated with mortality (adjHR 1.140, 95% CI 1.091-1.192). Moreover, this association tended to be stronger among younger patients, patients with fewer comorbidities and lower severity. The association between low ALC and mortality in original, PSM, IPTW, and CBPS populations were 1.497 (95% CI 1.320-1.697), 1.391 (95% CI 1.169-1.654), 1.512 (95% CI 1.310-1.744), and 1.511 (95% CI 1.310-1.744), respectively. Additionally, the association appears to be consistent, using distinct cutoff levels to define the low ALC. We identified that early low ALC was associated with increased one-year mortality in critically ill surgical patients, and prospective studies are warranted to confirm the finding.

Risk of cytomegalovirus infection and subsequent allograft failure after pancreas transplantation

Cytomegalovirus (CMV) is a common cause of infection after transplantation, but few studies have evaluated its epidemiology, risk factors, and outcomes among pancreas transplant recipients. We performed a retrospective cohort study of adults who underwent pancreas transplantation from January 1, 2010, through December 31, 2020, at 3 sites in Arizona, Florida, and Minnesota. The primary outcome was clinically significant CMV infection (csCMVi), defined as CMV disease or infection requiring antiviral therapy. The secondary outcome was pancreas allograft failure. Among 471 pancreas transplant recipients, 117 (24.8%) developed csCMVi after a median of 226 (interquartile range 154-289) days. CMV donor (D)+/R- patients had a significantly higher incidence of csCMVi (hazard ratio [HR] 4.01, 95% confidence interval [CI] 2.10-7.64; P < .001). In adjusted analysis, a lower absolute lymphocyte count (ALC) was associated with a greater risk of csCMVi among seropositive recipients (HR 1.39 per 50% decrease, 95% CI 1.13-1.73; P = .002) but not among D+/R- patients (HR 1.04 per 50% decrease, 95% CI 0.89-1.23; P = .595). csCMVi, lower ALC, and acute rejection (P < .001) were independently associated with pancreas allograft failure. In conclusion, CMV D+/R- was associated with csCMVi in pancreas recipients, although ALC was associated with csCMVi only among seropositive patients. The development of csCMVi in pancreas recipients was associated with poor pancreas allograft outcomes.

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

A Risk Prediction Model for Severe Radiation Induced Lymphopenia in Patients with Pancreatic Cancer Treated with Concurrent Chemoradiotherapy

In pancreatic cancer, radiation induced lymphopenia (RIL) is associated with a poor prognosis. However, normal tissue complication probability (NTCP) models predicting RIL in pancreatic cancer treated with concurrent chemoradiotherapy (CCRT) have yet to be developed. This study aims to develop a least absolute shrinkage and selection operator (LASSO)-based multivariate NTCP model to predict severe RIL in patients with pancreatic cancer during CCRT and to validate the model internally. We retrospectively reviewed patients with localized pancreatic cancer who underwent CCRT using three-dimensional conformal radiation therapy from 2013 to 2021. The exclusion criteria were patients with distant metastasis; patients who did not complete RT due to tumor progression; patients who did not have absolute lymphocyte count (ALC) data available before or during RT. An ALC of < 0.5 K/μL during CCRT was defined as severe RIL. A NTCP model of severe RIL was developed by LASSO-based multivariate analysis. We used age, sex, Karnofsky performance status, maximum tumor size, carbohydrate antigen 19-9 level before RT, ALC before RT, volume of planning target volume (PTV), and dosimetric parameters for surrounding organs (including spleen, vertebrae, liver, bilateral kidneys, gastrointestinal tracts) as variables for LASSO. In addition, internal validation was performed by the bootstrap method. The predictive performance of the model was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve and scaled Brier score. Of the 131 patients included in the study, the median age was 68 years (range, 42-84), and 55% were male. The median ALC before RT was 1.37 K/µL (0.52-3.50). The median PTV volume was 315.4 ml (86.3-1079.3). The median dose of radiotherapy was 50.4 Gy (16.2-50.4), with 1.8 Gy per fraction. Combination chemotherapy was S-1 in 99 cases (75.6%) and gemcitabine in 32 cases (24.4%). Induction chemotherapy before CCRT was performed in 39 patients (29.8%). Severe RIL was observed in 84 (63.6%) patients. The LASSO showed that low baseline ALC (p = 0.0002), large PTV volume (p < 0.0001), and a large kidney V5 defined as the percentage of bilateral kidneys receiving 5 Gy or more (p = 0.0338) were selected as parameters of the prediction model for severe RIL (AUC = 0.917) and scaled Brier score was 0.511. As a result of internal validation by the bootstrap method, the average AUC was 0.918 (95% confidence interval, 0.849-0.954). Severe RIL occurred frequently during CCRT for pancreatic cancer, and a NTCP model for severe RIL developed and validated internally in this study showed good predictive performance. External validation is needed before this NTCP model can be used as a benchmark for treatment planning to reduce the risk of severe RIL and for considering future treatment approaches.

All-Cause Mortality and Its Predictors in Haemato-Oncology Patients with Febrile Neutropenia.

Febrile neutropenia (FN) is one of the most important life-threatening complications in haemato-oncology. Our objective was to report all-cause mortality rates in patients ill with a hematological malignancy (HM) hospitalized with a first FN episode and to identify predictors for mortality. We conducted a historical retrospective cohort study of consecutive patients with an HM, >18 years of age, admitted between January 2012 and August 2018 for a first episode of FN. Data on all-cause mortality 12 months after admission for FN were obtained. The Kaplan-Meier curve was used to describe mortality during the follow-up period. Univariate and multivariable analyses identified predictors for 1,3 and 12-month mortality. One hundred and fifty-eight patients (mean age 69.5, 49.4% males) were included. Overall, 54 patients died (15.8%, 25.9%, and 34.1% died after 1, 3, and 12 months, respectively). Lower serum albumin, higher serum gamma-glutamyl transferase (GGT), lower estimated glomerular filtration rate (eGFR), older age, higher temperature, and lower absolute lymphocyte count at admission were independent predictors of all-cause mortality after 12 months. Further studies are needed to confirm our results and identify therapeutic strategies to improve survival.

Peripheral Blood Absolute Lymphocyte Count as a Predictor of Cytomegalovirus Infection in Kidney Transplant Recipients

Cytomegalovirus viremia and infection have been reported to increase the risks for acute graft rejection and mortality in kidney transplant recipients. Previous studies demonstrated that a lower absolute lymphocyte count in peripheral blood is associated with cytomegalovirus infection. The aim of this study was to investigate whether absolute lymphocyte count could predict cytomegalovirus infection in kidney transplant recipients. From January 2010 to October 2021, 48 living kidney transplant recipients in whom both donor and recipient were positive for immunoglobulin G of cytomegalovirus were included in this retrospective study. The primary outcome was defined as cytomegalovirus infection occurring ≥28 days after kidney transplantation. All recipients were followed for 1 year after kidney transplantation. The diagnostic accuracy of absolute lymphocyte count on day 28 post-transplantation for cytomegalovirus infection was analyzed using receiver operating characteristic curves. A Cox proportional hazards model was used to calculate hazard ratios for the incidence of cytomegalovirus infection. There were 13 patients (27%) with cytomegalovirus infection. The sensitivity and specificity for cytomegalovirus infection were 62% and 71%, respectively; the negative predictive value was 83% when an absolute lymphocyte count of 1100 cells/μL on day 28 post-transplantation was used as the cutoff. The incidence of cytomegalovirus infection was significantly higher when the absolute lymphocyte count was <1100 cells/μL on day 28 post-transplantation (hazard ratio, 3.32; 95% CI, 1.08-10.2). Absolute lymphocyte count is an inexpensive and easy test that can effectively predict cytomegalovirus infection. Further validation is needed to confirm its utility.

CD4+ and CD8+ cell counts are significantly correlated with absolute lymphocyte count in hospitalized COVID-19 patients: a retrospective study.

Coronavirus disease 2019 (COVID-19) is a contagious respiratory illness that was declared a pandemic in March 2020. Lymphopenia is one of the specific laboratory results disturbance in COVID-19 patients. Such findings are frequently associated with substantial changes in T-cell counts, particularly CD4+ and CD8+ T-cells. This study aimed to examine the correlation between CD4+ and CD8+ cell counts and absolute lymphocyte count (ALC) in COVID-19 patients and analyze its difference based on the COVID-19 patients' severity. From March 2022 to May 2022, we conducted a retrospective cohort study using medical records and laboratory data from patients diagnosed with COVID-19 at our hospital who met the inclusion and exclusion criteria. The total sampling method was used to recruit study participants. We conducted bivariate analysis, which consisted of correlation and comparative analysis. Thirty-five patients met the inclusion and exclusion criteria and were divided into two severity groups (mild-moderate and severe-critical). The findings of this study revealed a significant correlation between CD4+ cell count and ALC on admission (r = 0.69, p < 0.001) and the tenth day of onset (r = 0.559, p < 0.001). Similarly, there was a correlation between CD8+ and ALC at admission (r = 0.543, p = 0.001) and on the tenth day of onset (r = 0.532, p = 0.001). Individuals with severe-critical illness had lower ALC, CD4+, and CD8+ cell counts than those with mild-moderate illness. According to the findings of this study, there is a correlation between CD4+ and CD8+ cell counts and ALC in COVID-19 patients. All lymphocyte subsets also showed a lower value in severe forms of the disease.

Clinical presentation, ICU management and outcome in severe COVID-19 disease – A prospective observational study

Aim: We conducted a prospective, observational study to describe the clinical characteristics, management, and outcomes of patients with moderate to severe coronavirus disease admitted to the Intensive Care Unit (ICU). Methods: The study was conducted from 1st July 2020 to 31st December 2020. The criteria for ICU admission included a positive Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) for the novel Coronavirus (SARS-CoV-2) and oxygen saturation of less than 90% with or without oxygen. Results: A total of 621 patients were included (median age, 59 years [interquartile range {IQR}, 48-68]; 75.8% were males. The common comorbidities were hypertension (323 [52%]), and diabetes mellitus. 96 (15.5%) patients underwent mechanical ventilation, 18 (2.9%) received renal replacement therapy, and 223 (36%) died. The median age in non-survivors was significantly higher [63 years (IQR 55-71)] vs. 57 years (IQR 46-66)] (p &lt; 0.001). Hypoxia (oxygen saturation (SpO2 &lt; 90%) and shortness of breath suggestive of impending respiratory failure were the most common symptoms necessitating ICU admission. A low absolute lymphocyte count (ALC), and high levels of inflammatory biomarkers which persisted for seven days after diagnosis were significantly associated with non-survival. Multivariate logistic regression analysis showed shortness of breath (SOB), hypoxia (SpO2 &lt; 90% on oxygen), use of neuromuscular blockers, and chronic kidney disease as independent risk factors associated with mortality as were the severity scores (APACHE and SOFA). Conclusion: This single-center case series provides clinical characteristics and outcomes of patients with confirmed COVID-19 disease admitted to the COVID ICU. These findings are important for guiding research and preparing for future pandemics.

Retreatment with nivolumab and ipilimumab with or without chemotherapy in patients with metastatic non-small cell lung cancer after progression on immune checkpoint inhibitor therapy.

e21192 Background: The advent of immune checkpoint inhibitor (ICI) has revolutionized the therapeutic arsenal for metastatic non-small cell lung cancer. However, better therapeutic options after a progression on frontline ICIs are urgently needed and remain to be defined. ICI retreatment (rt) may constitute a rational therapeutic alternative in these patients. However prospective studies evaluating such opportunity are still lacking. Methods: We retrospectively collected data from 30 metastatic NSCLC patients (pts) having progressed on ICI (anti-PD-1, anti-PD-L1 or anti-PD-1/anti-CTLA4 combined or not with histologydriven chemotherapy) who were retreated by double-agent ICI (ipilimumab and nivolumab) combined or not with histology-driven ChT in order to evaluate rt overall survival (OS) and rt progression-free-survival (PFS). The rt PFS was calculated from rt ICI initiation to death, last follow-up or disease progression. An assessment of correlation between certain clinical variables like sex, age, smoking history and others; and survival variables was performed. Results: The median age of the 30 pts included in the analysis was 64 years (63% of pts were &lt; 70 years old and 37% ≥ 70 years old) and 53% (n = 16) of the pts were male. Most suffered from a non-sq NSCLC (73%), with bone mets (66%), and were current or former smokers (90%). Median OS and median PFS in the whole group were 9 months (m) [95% confidence interval (CI): 5.7 - 14] and 2.5 m [95% CI: 2 - 4.6] respectively. Retreatment PFS was higher in pts having received dual ICI combined with ChT than dual ICI only [95% CI: 4.3 (3.7 – 6) versus 2.1 (1.5 – 2.9) m; hazard ratio (HR): 0.51 (0.24 – 1.10); p – value (p) = 0.085]. Retreatment OS and PFS were numerically higher in pts having received single- or double- ICI as prior therapy compared to ICI plus ChT [9.6 (6.4 – not reached) m versus 8.4 (3.7 – 13.5) m; HR: 0.53 (0.22 – 1.29), p = 0.15], and [4.2 (2.2 – not reached) m versus 2.4 (2 – 4.5 m); HR: 0.56 (0.25 – 1.24); p = 0.14), respectively], regardless of the rt. When we assessed the correlation between prior therapy and rt, we found the association of ChT to dual-ICI after prior single- or dual-ICI as first line treatment leads to a significantly higher PFS [4.5 (4 – NR) m versus 2.5 (1.6 – NR) m] compared to pts having received first ChT plus ICI then dual-ICI alone as second line treatment [HR 0.35 (95% CI: 0.13 – 0.93); p: 0.03]. The trend in OS benefit probably also favored ChT with dual-ICI as rt after prior single- or dual-ICI (HR 0.55; p = 0.23). Binary variables such as sex, histology, PD-L1 expression, smoking history, therapeutic discontinuation interval (TDI), baseline derived neutrophil-to-lymphocyte ratio dNLR) and baseline absolute lymphocyte counts (ALC) influenced positively the PFS in pts receiving dual ICI combined with ChT [ sex HR: 0.28; non-squamous histology HR: 0.26; PDL1 expression HR:0.22; former smoker HR: 0.23; never-smoker HR: 0.40; TDI less than 30 days HR: 0.09; high (≥ 3) dNLR HR: 0.22; and low (&lt;1000) ALC HR: 0.37]. Conclusions: Patients previously treated by ICI could be retreated by ICI combined with histology-driven chemotherapy in an individual approach, under certain circumstances, which are yet to be formally evaluated and determined.

Prophylactic cranial irradiation-related lymphopenia affects survival in patients with limited-stage small cell lung cancer

BackgroundThe study aimed to identify the relations of the absolute lymphocyte count (ALC) nadir during prophylactic cranial irradiation (PCI) and patient outcomes in limited-stage small cell lung cancer (LS-SCLC). MethodsWe analyzed 268 L S-SCLC patients who underwent PCI from 2012 to 2019. ALC values were collected prior, during, and 3 months post PCI. Kaplan–Meier and Cox regression analyses were performed to assess the relation of ALC to patient prognosis. Two nomograms were developed on the basis of clinical variables for survival prediction. ResultsCompared with the ALC before PCI (1.13 × 109 cells/L), the ALC nadir during PCI was significantly reduced by 0.68 × 109 cells/L (P < 0.001) and raised to 1.02 × 109 cells/L 3 months post PCI. Patients with a low ALC nadir during PCI (<0.68 × 109 cells/L) had inferior progression free survival (PFS) (median PFS: 17.2 m vs. 43.7 m, P = 0.019) and overall survival (OS) (median OS: 29.0 m vs 39.1 m, P = 0.012). Multivariate Cox analysis revealed that age, smoking history, clinical stage, and ALC nadir were independent OS (P = 0.006, P = 0.005, P < 0.001 and P = 0.027, respectively), as well as independent PFS predictors (P = 0.032, P = 0.012, P = 0.012 and P = 0.018, respectively). After internal cross-validation, the corrected concordance indices of the predictive nomograms for PFS and OS were 0.637 and 0.663, respectively. ConclusionLS-SCLC patients with a low ALC nadir during PCI likely have worse survival outcomes. Dynamic evaluation of the ALC during PCI is recommended for LS-SCLC patients.