Higher Absolute Lymphocyte Count Research Articles

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.

Monitoring trends in the absolute lymphocyte count and the neutrophil-to-lymphocyte ratio in patients with breast cancer receiving eribulin

BackgroundStudies have shown that the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR) are related to the outcomes in patients with breast cancer receiving specific chemotherapies. However, the reports have focussed on the initial blood test and there is a lack of evidence or data to support that dynamic changes of ALC or NLR are associated with the patients’ survival outcomes.MethodsWe retrospectively reviewed electronic medical records from patients with breast cancer treated with eribulin from 2015 to 2019 at our institution. Blood test data were available prior to starting eribulin (baseline), and at 1, 3 and 6 months after initiating eribulin. We classified the patients into ALC and NLR high and low groups using the following cut-offs: 1000/µl for ALC and 3 for NLR. We defined ALC and NLR trends as increasing or decreasing compared with the initial data. We assessed the associations between the ALC and NLR with progression-free survival and overall survival.ResultsThere were 136 patients with breast cancer treated with eribulin. Of these patients, 60 had complete blood tests and follow-up data. Neither a high ALC nor a low baseline NLR was associated with the survival outcome. One month after initiating eribulin treatment, a high ALC and a low NLR were significantly associated with longer progression-free survival (p = 0.044 for each). Three months after initiating eribulin, a high ALC was significantly associated with better overall survival (p = 0.006). A high NLR at 3 or 6 months after initiating eribulin was associated with worse overall survival (p = 0.017 and p = 0.001, respectively). The ALC and NLR trends across times were not associated with survivals.ConclusionWe showed that 1, 3 and 6 months after initiating eribulin, a high ALC and a low NLR may be related to the patients’ survival outcomes. The ALC and NLR trends were not associated with survival. Accordingly, we believe patients who maintain a high ALC and a low NLR may have better clinical outcomes after initiating eribulin.

A Composite Score for Predicting Vertical Transmission of Hepatitis C: A Multicenter Study.

Prevention of the vertical transmission of the hepatitis C virus (HCV) presents an obstetric challenge. There are no approved antiviral medications for the treatment or prevention of HCV for pregnant patients. We aimed to create a composite score to accurately identify a population of pregnant patients with HCV who have high potential for vertical transmission. In a retrospective, multicenter cohort study, we identified pregnant patients with hepatitis C with linked data to their infants who have had HCV RNA or HCV antibody testing. Demographic data, including age and race/ethnicity, as well as clinical and laboratory data, including tobacco/alcohol use, infections, liver function tests, the HCV RNA titer, HCV antibody, HCV genotype, absolute lymphocyte count, and platelet count, were collected. Data were analyzed using logistic regression and receiver operating characteristics (ROCs) and internally validated using the forward selection bootstrap method. We identified 157 pregnant patients and 163 corresponding infants. The median maternal delivery age was 29 (IQR: 25-33) years, and the majority (141, or 89.8%) were White. A high HCV RNA titer, high absolute lymphocyte count, and high platelet count were associated with vertical transmission. A high HCV RNA titer had an AUROC of 0.815 with sensitivity, specificity, a positive predictive value, and a negative predictive value of 100.0%, 59.1%, 17.6%, and 100.0%, respectively. A composite score combining the three risk factors had an AUROC of 0.902 (95% CI = 0.840-0.964) but with a risk of overfitting. An HCV RNA titer alone or a composite score combining the risk factors for HCV vertical transmission can potentially identify a population of pregnant patients where the rate of vertical transmission is high, allowing for potential interventions during antepartum care.

Baseline Circulating Blood Cell Counts and Ratios and Changes Therein for Predicting Immune-Related Adverse Events during Immune Checkpoint Inhibitor Therapy: A Multicenter, Prospective, Observational, Pan-Cancer Cohort Study with a Gender Perspective.

Several factors have been associated with the occurrence of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) therapy. Despite their availability, the predictive value of circulating blood cell parameters remains underexplored. Our aim was to investigate whether baseline values of and early changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC), other blood cell counts, and lymphocyte-related ratios can predict irAEs and whether sex may differentially influence this potential predictive ability. Of the 145 patients included, 52 patients (35.8%) experienced at least one irAE, with a 1-year cumulative incidence of 41.6%. Using Fine and Gray competing risk models, we identified female sex (hazard ratio (HR) = 2.17, 95% confidence interval (CI) = 1.20-3.85), high ALC before ICI initiation (HR = 1.63, 95% CI = 1.09-2.45), and low ANC after ICI initiation (HR = 0.81, 95% CI = 0.69-0.96) as predictors of irAEs. However, ALC and ANC may only have an impact on the risk of irAEs in women (stratified for female sex, ALC-related HR = 2.61, 95% CI = 1.40-4.86 and ANC-related HR = 0.57, 95% CI = 0.41-0.81). Priority should be given to developing models to predict ICI-related toxicity and their validation in various settings, and such models should assess the impact of patient sex on the risk of toxicity.

Full Blood Count Parameters in COVID-19 Patients With Disease Severity, Patient Outcome and Vaccination Status

Introduction: A link between full blood count (FBC) parameters with the severity and prognosis of individuals with coronavirus disease 2019 (COVID-19) infection is shown. We aim to identify changes in FBC parameters depending on patients’ characteristics, the severity of the disease and vaccination status. Methods: A cross-sectional retrospective laboratory study is done on 208 respondents who were selected from February 2021 to December 2022 in the Pathology Department of the Tuanku Ja’afar Hospital in Negeri Sembilan. All patients are confirmed COVID-19 positive by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of pharyngeal and nasal swab specimens. Patients are further classified based on their COVID clinical stages, severity, vaccination status and outcome. The statistical data are analysed using IBM SPSS version 27. Results: Severe patients have significantly lower absolute lymphocyte count (ALC), absolute monocyte count (AMC), absolute eosinophil count (AEC) and absolute basophil count (ABC) but higher mean platelet volume (MPV), absolute neutrophil count (ANC), neutrophil to lymphocyte ratio (NLR) and immature granulocytes (IG) compared to non-severe patients (p < 0.05). Similar findings are seen among non-survivors (p < 0.05). Fully vaccinated patients have significantly lower NLR and MPV but higher ALC, AMC, AEC and ABC than unvaccinated or partially vaccinated patients (p < 0.05). Conclusion: Selected FBC parameters of COVID-19 patients (platelets, ANC, NLR, MPV, ALC, AMC, AEC, and ABC) are significantly different depending on patients’ severity, outcome and vaccination status. These results might give a clear insight for clinicians to anticipate the severity and outcome of patients based on the patient’s FBC parameters.

Response to Mosunetuzumab in Patients with B-Cell Lymphomas Relapsed or Refractory after CAR-T Cell Therapy Is Associated with Changes in Lymphocyte Counts

Introduction: Mosunetuzumab is a CD20/CD3 bispecific antibody that redirects endogenous T cells to kill malignant B cells by concomitantly binding to CD3 on T cells and CD20 on B cells. A multicenter phase I/II study evaluating mosunetuzumab in relapsed/refractory (r/r) non-Hodgkin lymphomas, including patients r/r after chimeric antigen receptor-modified T-cell therapies (CAR-T), was the basis for FDA approval for mosunetuzumab in follicular lymphoma (NCT02500407; Budde et al. Lancet Oncol 2022). We retrospectively assessed the impact of mosunetuzumab on lymphocyte counts and CAR T cells in responding and non-responding patients. Methods: Samples were collected prospectively from participants enrolled on NCT02500407 and exploratory post hoc analyses were performed on a subset of patients who had received prior CAR-T. P-values unadjusted for multiple comparisons are reported. We examined changes in absolute lymphocyte counts (ALC) and CAR-T transgene levels, as well as CD4 counts and CD8 counts, at baseline (C1D1) and prior to cycle 2 day 1 (C2D1) of mosunetuzumab. We also examined length of time from CAR-T to mosunetuzumab. CAR transgene levels were assessed by quantitative PCR. Results: 30 patients had cycle 1 day 1 (C1D1) and C2D1 paired samples available for analysis. 27 patients had large B-cell lymphoma (90%) and 3 patients had low-grade follicular lymphoma (10%). The doses of mosunetuzumab received ranged from 6mg - 60mg IV or 1.6mg - 20mg SC. The median time from CAR-T infusion to mosunetuzumab was 161 days (range: 35-1071); 40% of patients (12/30) received mosunetuzumab within 100 days of CAR-T, 43% of patients (13/30) received mosunetuzumab > 100-days to 1 year after CAR-T, and 17% (5/30) of patients received mosunetuzumab > 1 year after CAR-T infusion. We found that patients who responded to mosunetuzumab had a longer time from CAR-T infusion than non-responders (mean 342 days [range: 98-587] vs 110 days [range: 70-150], respectively, p = 0.02). Although there was no difference in baseline ALC, we found that responding patients had higher ALCs on C2D1 (p=0.005). For 15 patients with available T-cell subsets, CD4 counts were higher on C2D1 for responders (p=0.05). We also investigated changes in CAR transgene levels. 14/20 patients who received commercially available standard of care CAR-T products had detectable CAR transgene levels vs only 1/10 patients who received an investigational CAR-T due to assay limitations. Thus, we examined changes in CAR transgene levels in those patients who had received commercially available standard of care CAR-T (n=20). No difference was observed between responders and non-responders in CAR transgene copy numbers at baseline; however, on C2D1 after one cycle of mosunetuzumab, non-responding patients had a trend toward decrease in CAR transgene levels while responding patients had persistence or increase in CAR transgene levels (p=0.07). Conclusions: We observed higher peripheral blood lymphocytes after one cycle of mosunetuzumab in responding patients. Of interest, an increase in lymphocytes in responding patients had previously been described after blinatumomab (Klinger et al. Blood 2012). These findings may indicate a class effect of bispecific antibodies in general. We also found that patients who were r/r to CAR-T and responding to mosunetuzumab had a trend towards an increase in CAR transgene levels compared with patients not responding to mosunetuzumab. This suggests an interaction between CAR-T cells and bispecific antibodies. Finally, it is notable that post-CAR patients responding to mosunetuzumab had a longer time from CAR-T infusion, perhaps reflecting recovery from lymphodepletion. Further investigations are needed to understand the mechanism(s) behind these observations.

Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

Not all patients with advanced non-small cell lung cancer (NSCLC) benefit from immune checkpoint inhibitors (ICIs). Therefore, we aimed to assess the predictive potential of gene expression profiling (GEP), peripheral immune cell counts, and clinical characteristics. The primary endpoint of this prospective, observational study was a durable clinical benefit (DCB) defined as progression-free survival >6 months. In a subgroup with histological biopsies of sufficient quality (n = 25), GEP was performed using the nCounter® PanCancer IO 360 panel. DCB was observed in 49% of 123 included patients. High absolute lymphocyte count (ALC) and absence of liver metastases were associated with DCB (OR = 1.95, p = 0.038 and OR = 0.36, p = 0.046, respectively). GEP showed clustering of differentially expressed genes according to DCB, and a strong association between PD-L1 assessed by GEP (CD274) and immunohistochemistry (IHC) was observed (p = 0.00013). The TGF-β, dendritic cell, and myeloid signature scores were higher for patients without DCB, whereas the JAK/STAT loss signature scores were higher for patients with DCB (unadjusted p-values < 0.05). ALC above 1.01 × 109/L and absence of liver metastases were significantly associated with DCB in ICI-treated patients with NSCLC. GEP was only feasible in 20% of the patients. GEP-derived signatures may be associated with clinical outcomes, and PD-L1 could be assessed by GEP rather than IHC.

COVID-19 Disease in Pediatric Solid Organ Transplantation from Alpha to Omicron: A High Monocyte Count in the Preceding Three Months Portends a Risk for Severe Disease.

Planning for future resurgences in SARS-CoV-2 infection is necessary for providers who care for immunocompromised patients. to determine factors associated with COVID-19 disease severity in immunosuppressed children. a case series of children with solid organ transplants diagnosed with SARS-CoV-2 infection between 15 March 2020 and 31 March 2023. a single pediatric transplant center. all children with a composite transplant (liver, pancreas, intestine), isolated intestine transplant (IT), isolated liver transplant LT), or simultaneous liver kidney transplant (SLK) with a positive PCR for SARS-CoV-2. SARS-CoV-2 infection. We hypothesized that children on the most immunosuppression, defined by the number of immunosuppressive medications and usage of steroids, would have the most severe disease course and that differential white blood cell count in the months preceding infection would be associated with likelihood of having severe disease. The hypothesis being tested was formulated during data collection. The primary study outcome measurement was disease severity defined using WHO criteria. 77 children (50 LT, 24 intestine, 3 SLK) were infected with SARS-CoV-2, 57.4 months from transplant (IQR 19.7-87.2). 17% were ≤1 year post transplant at infection. 55% were male, 58% were symptomatic and ~29% had severe disease. A high absolute lymphocyte count at diagnosis decreased the odds of having severe COVID-19 disease (OR 0.29; CI 0.11-0.60; p = 0.004). Conversely, patients with a high absolute monocyte count in the three months preceding infection had increased odds of having severe disease (OR 30.49; CI 1.68-1027.77; p = 0.033). Steroid use, higher tacrolimus level, and number of immunosuppressive medications at infection did not increase the odds of having severe disease. The significance of a high monocyte count as predictor of severe disease potentially confirms the importance of monocytic inflammasome-driven inflammation in COVID-19 pathogenesis. Our data do not support reducing immunosuppression in the setting of infection. Our observations may have important ramifications in resource management as vaccine- and infection-induced immunity wanes.

Increased absolute lymphocyte count, increased absolute neutrophil count and low platelet to lymphocyte ratio as predicting factors in the superior disease control of refractory/relapsing gynecologic malignancies with anti PD-1 therapy: 10 years of experience in a single institution

ObjectiveImmune checkpoint inhibitors are rapidly being used in solid and hematologic malignancies, including gynecologic cancers. The high mortality and relapsing rates of advanced gynecologic malignancies remain a challenging issue. This study aimed to identify the predicting factors associated with survival prognosis and disease control in patients with refractory/relapsing (R/R) gynecologic malignancies receiving anti PD-1 therapy. Materials and methodsWe retrospectively reviewed the medical records of 49 patients diagnosed with R/R gynecologic malignancies between July 2012 and June 2019 in Chang Gung Memorial Hospital, Taiwan. Among the 49 patients, 6 were excluded due to incomplete medical records or not receiving anti PD-1 therapy. The remaining 43 patients were further divided into responsive and non-responsive groups according to disease control for predicting prognostic factor analysis. ResultsFor the 43 cases, the median age at diagnosis and disease follow-up length were 54 years and 29 months, respectively. Among them, 23 (53%) were categorized into the responsive group, and the remaining 20 (47%) were categorized into the non-responsive group. The mortality rates were 17% and 25% in the responsive and non-responsive groups, respectively. The responsive group had significantly higher absolute lymphocyte count (ALC), higher absolute neutrophil count (ANC) and low platelet to lymphocyte ratio (PLR) than the non-responsive group. A superior long-term survival trend was also observed in the responsive group, but the difference was not statistically significant. ConclusionsThis study reinforced the hypothesis that high ALC, high ANC and low PLR are associated with superior disease control in patients with R/R gynecologic malignancies receiving anti PD-1 therapy.

Neutrophil-, Monocyte- and Platelet-to-Lymphocyte Ratios, and Absolute Lymphocyte Count for Diagnosis of Malignant Soft-tissue Tumors.

Soft-tissue tumors are difficult to differentiate as benign or malignant. Immune markers, such as the neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and absolute lymphocyte count (ALC) in serum, have been reported to be useful in the diagnosis and predicting prognosis of several malignancies. We investigated the diagnostic value of these immune markers in differentiating soft-tissue tumors. A total of 692 patients who underwent biopsy or surgery of soft-tissue tumors were included and divided into benign tumor, low-grade malignancy, or high-grade malignancy groups. Immune markers were calculated from the preoperative blood tests and compared between the groups. A receiver operating curve (ROC) analysis was conducted between the benign disease group and a combination of the groups with malignancy to determine which immune marker had the most diagnostic value. NLR and MLR were significantly different between the three groups with benign disease having the lowest value and high-grade malignancies the highest. Benign disease was also associated with lower PLR and higher ALC. There was no difference between the low- and high-grade malignancies in PLR and ALC. From the ROC analysis, NLR had the highest area under the curve (AUC) value of 0.773 out of the four markers. When limited to small tumors (≤30 mm), NLR had the highest AUC value of 0.729. The NLR showed the highest diagnostic value, although the diagnostic ability was not adequately high to differentiate benign and malignant soft-tissue tumors alone. NLR may serve as diagnostic support in combination with clinical history, physical findings, and tumor-imaging results.

Challenges in synergizing radiotherapy with immunotherapy to unlock the abscopal effect in metastatic NSCLC: A systematic review

BackgroundWith the recent success of immunotherapy, there is a growing interest in combining radiation with immunotherapy to boost abscopal response rates. Several challenges exist in determining how to synergize these two modalities in the treatment of metastatic NSCLC. MethodsReferences for this review were identified through searches of MEDLINE/PubMed and Clinicaltrials.gov databases with the search terms “abscopal”, “radiation OR radiotherapy,” “NSCLC”, and “lung” on the index date of July 2022 from 2000-2022. This systematic review focuses primarily on clinical papers. DiscussionEarly work combining radiotherapy with immunotherapy show promise in unlocking the abscopal effect. Preliminary evidence suggests that radiotherapy regimens with <5 fractions and smaller fields may be superior to regimens with 15 fractions and larger fields. There does not appear to be enough evidence to draw conclusions about the optimal timing of radiotherapy in relation to immunotherapy or the optimal anatomical location of radiation to induce the abscopal effect. Several studies suggest selecting patients with a higher absolute lymphocyte count (ALC) and lower neutrophil-to-lymphocyte ratio (NLR) may help to further boost abscopal response rates. Furthermore, selecting tumors with programmed death ligand-1 (PD-L1) expression, mismatch repair deficiency, and higher tumor mutational burden may similarly achieve this goal. Lastly, additional work is needed to minimize and predict for severe toxicity associated with combination therapy.

Prognostic value of prelymphodepletion absolute lymphocyte counts in relapsed/refractory diffuse large B-cell lymphoma patients treated with chimeric antigen receptor T cells.

Chimeric antigen receptor (CAR) T cell therapy has achieved unprecedented efficacy recently. However, the factors related to responses and durable remission are elusive. This study was to investigate the impact of pre-lymphodepletion (pre-LD) absolute lymphocyte count (ALC) on CAR T cell therapy outcomes. We conducted a retrospective study of 84 patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who underwent CAR T cell treatment at the Affiliated Hospital of Xuzhou Medical University between March 1,2016 and December 31, 2021. The enrolled patients were divided into high group and low group according to the optimal cutoff value of pre-LD ALC. The Kaplan-Meier analyses was used to calculate survival curves. The Cox proportional hazards model was used for univariate and multivariate analysis to assess the prognostic factors. The ROC showed that the optimal cutoff value of pre-LD ALC was 1.05 x 109/L. The overall response (defined as partial response or complete response) rate was significantly higher in patients with a high pre-LD ALC (75% versus 52.08%; P=0.032). Patients with a low pre-LD ALC had significantly inferior overall survival (OS) and progression-free survival (PFS) compared with those having a high pre-LD ALC (median OS, 9.6 months versus 45.17 months [P=0.008]; median PFS, 4.07 months versus 45.17 months [P= 0.030]). Meanwhile, low pre-LD ALC is an independent risk factor for PFS and OS. The data suggested that pre-LD ALC may serve as a helpful indicator to predict the outcomes of CAR T cell therapy in patients with R/R DLBCL.

Prognostic Value of Absolute Lymphocyte Count in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab Plus Ipilimumab

Nivolumab and ipilimumab (NIVO + IPI) is standard therapy for patients with advanced renal cell carcinoma (RCC). Absolute lymphocyte count (ALC) is a valuable prognostic factor in patients with various cancers treated with immune checkpoint inhibitors. Herein, we determined the prognostic value of pretreatment ALC in advanced RCC patients treated with NIVO + IPI as first-line therapy. Data from 46 advanced RCC patients treated with NIVO + IPI between September 2018 and August 2022 were retrospectively reviewed and analyzed. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with low than high ALC (PFS: p = 0.0095; OS: p = 0.0182). Multivariate analysis suggested that prior nephrectomy [hazard ratio (HR) = 3.854, 95% confidence interval (CI) = 1.433-10.359, p = 0.0075] and pretreatment ALC (HR = 2.513, 95% CI = 1.119-5.648, p = 0.0257) were independent factors for PFS. Our new prognostic ALNx model based on ALC and prior nephrectomy suggested that the poor-risk group was a predictor of significantly worse PFS (p < 0.0001) and OS (p = 0.0016). Collectively, the developed ALNx model may be a novel predictor of response in advanced RCC patients treated with NIVO + IPI.

Abstract P5-02-23: Association of Neutrophil-to-Lymphocyte Ratio and Absolute Lymphocyte Count with Clinical Outcomes for Patients with Advanced Breast Cancer in the MONARCH 2 Trial

Abstract Background: Pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) are putative prognostic factors in patients with advanced breast cancer (ABC). Little information is available on the prognostic value of these immune status markers in patients treated with abemaciclib (ABE). In this study, we investigated the relationship between baseline NLR and ALC and clinical outcomes using data from the phase 3 MONARCH 2 (M2) trial. Methods: The M2 study compared ABE/fulvestrant to placebo (PBO)/fulvestrant in patients with estrogen-receptor positive, human epidermal growth factor receptor 2-negative ABC that had progressed on prior endocrine therapy. The current post hoc analyses used baseline laboratory data and outcome data from the June 20, 2019, cutoff date (median follow-up: 47.7 months). For both baseline NLR and baseline ALC, patients were divided into high and low categories, defined by a cutoff of 2.5 for NLR and 1.5 × 109/L for ALC. The association of baseline NLR and ALC with investigator-assessed progression-free survival (PFS) and overall survival (OS) was explored using Cox models stratified by treatment and described using Kaplan-Meier estimates. After assessing the prognostic value of baseline NLR and ALC for PFS and OS using a univariate analysis, a multivariate model was used to determine whether baseline NLR and ALC were independently prognostic considering additional baseline and disease characteristic factors. Results: Data were available for 426 and 219 patients in the ABE and PBO arms, respectively. Median baseline NLR was 2.5 and 2.4 in the ABE and PBO arms, respectively. Median baseline ALC was 1.4 × 109/L in both arms. The numbers of patients categorized into the high and low categories were well balanced for analysis of both NLR and ALC. Univariate analyses showed that baseline NLR (&amp;lt; 2.5, ≥2.5) was a prognostic factor for PFS and OS (2-sided p&amp;lt; 0.0001). Patients with low baseline NLR consistently had better PFS and OS than those with high baseline NLR, and the treatment effect of ABE against PBO was consistently observed regardless of NLR category (Table 1). Univariate analyses showed that baseline ALC (&amp;lt; 1.5 × 109/L, ≥1.5 × 109/L) was also a prognostic factor for PFS and OS (2-sided p=0.0116 and 0.0032, respectively). PFS and OS were better for patients with high baseline ALC than for those with low baseline ALC, and the treatment effect of ABE against PBO was observed regardless of ALC category (Table 1). For PFS, the multivariate model was adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS), tumor grade, presence of liver metastasis, and bone-only disease. For OS, the multivariate model was adjusted for sensitivity to endocrine therapy, ECOG PS, presence of liver metastasis, and bone-only disease. When adjusting for these additional prognostic factors, baseline NLR, but not baseline ALC, remained statistically significant in the multivariate model (2-sided p&amp;lt; 0.0001). Conclusions: These exploratory analyses suggest that while both baseline NLR and ALC are prognostic of clinical outcomes, only baseline NLR is independently prognostic of PFS and OS. Low baseline NLR was associated with better PFS and OS outcomes, but the benefit of adding ABE to fulvestrant was similar regardless of baseline NLR status. Table 1. Summary of outcomes by treatment arm for NLR and ALC categories ALC, absolute lymphocyte count; CI, confidence interval; NLR, neutrophil-to-lymphocyte ratio; NR, not reached; OS, overall survival; PFS, progression-free survival. Citation Format: Eriko Tokunaga, Yasuo Miyoshi, Koji Dozono, Tsutomu Kawaguchi, Masakazu Toi. Association of Neutrophil-to-Lymphocyte Ratio and Absolute Lymphocyte Count with Clinical Outcomes for Patients with Advanced Breast Cancer in the MONARCH 2 Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-23.

Comparison of real-world outcomes following immunotherapy in recurrent or metastatic head and neck squamous cell carcinoma with outcomes of randomized controlled trials.

Evaluate outcomes of patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy (IO). Among patients with R/M HNSCC treated with IO in this retrospective single-institution cohort, Cox regression was used to compare overall survival (OS) for those with platinum-refractory disease and those treated in the first-line setting with OS from KEYNOTE-040/048, respectively. Multivariable Cox regression was used to identify predictors of OS. There was no significant OS difference for those treated in the platinum-refractory setting when compared to patients on KEYNOTE-040 (HR=1.22, p=0.27), nor for the first-line setting compared to KEYNOTE-048 (HR=1.23, p=0.19). ECOG-PS 1 (HR=2.00, p=0.02) and ECOG-PS 2 (HR=3.13, p < 0.01) were associated with worse OS. Higher absolute lymphocyte count (ALC) was associated with improved OS (HR=0.93 per 100 cells/μL, p=0.03). Real-world outcomes of IO in R/M HNSCC are similar to outcomes in randomized control trials, with performance status and ALC correlating with OS.

The predictive value of hematological markers in renal cell carcinoma.

621 Background: Renal cell carcinoma (RCC), which accounts for about 3% of adult malignancies, is regarded as a major cause of morbidity and mortality. The neutrophil-lymphocyte ratio (NLR) is a simple, reliable, and cost-effective biomarker of systemic inflammation that has been linked to oncologic outcomes in a variety of malignancies. The objective of this study is to determine whether NLR, along with other hematological parameters such as absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophil count (AEC), absolute monocyte count (AMC), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and the Systemic Immune-Inflammation Index (SII; defined as neutrophils counts X platelets counts divided by lymphocyte count), are related to baseline distant metastases and overall survival (OS) in RCC patients. Methods: Clinical data from 203 RCC patients treated at King Hussein Cancer Center (Amman, Jordan) were retrospectively reviewed. We examined the relationship between age, sex, ANC, AMC, ALC, AEC, NLR, MLR, PLR, and SII with baseline distant metastasis and patients’ OS. Results: Of the 203 patients, 97 patients (48.5%) were stage 4 at the time of diagnosis. Univariate analysis showed that patients with high baseline ANC (&gt;5400), AMC (&gt;600), AEC (&gt;120), NLR (&gt;4.36), MLR (&gt;0.33), PLR (&gt;140.44), WBC count (&gt;8.2), SII (&gt;757.7) and low baseline ALC (≤1900) had more baseline metastasis. (p-value: &lt;0.001, 0.007, 0.020, &lt;0.001, &lt;0.001, &lt;0.001, 0.006, &lt;0.001, and 0.004, respectively). On multivariate analysis, patients who had elevated NLR (&gt;4.36) were more likely to have distant metastasis at the time of diagnosis (p-value = 0.0076, odds ratio (OR): 4.45, CI: 1.49–13.33). Moreover, univariate and multivariate analysis showed that patients with elevated NLR (&gt;4.36) were associated with poorer OS (p-value: &lt;0.0001 and 0.0065, respectively). In addition, patients with elevated baseline ANC, AMC, MLR, PLR, SII, WBC count, and low ALC values were associated with poorer OS (p-value: &lt;0.0001, 0.0234, &lt;0.0001, &lt;0.0001, &lt;0.0001, 0.0290, and &lt;0.0001, respectively). Conclusions: The results of this study indicate a substantial correlation between several hematological parameters, including NLR, with the presence of distant metastases at the time of diagnosis and OS. Further research is required to uncover whether these hematological markers may be used to identify patients who are more likely to develop metastases and predict treatment response.

Lymphopenia at the time of transplant is associated with short-term mortality after deceased donor liver transplantation

Absolute lymphocyte count (ALC) is considered a surrogate marker for nutritional status and immunocompetence. We investigated the association between ALC and post-liver transplant outcomes in patients who received a deceased donor liver transplant (DDLT). Patients were categorized by ALC at liver transplant: low (<500/μL), mid (500-1000/μL), and high ALC (>1000/μL). Our main analysis used retrospective data (2013-2018) for DDLT recipients from Henry Ford Hospital (United States); the results were further validated using data from the Toronto General Hospital (Canada). Among 449 DDLT recipients, the low ALC group demonstrated higher 180-day mortality than mid and high ALC groups (83.1% vs 95.8% and 97.4%, respectively; low vs mid: P = .001; low vs high: P < .001). A larger proportion of patients with low ALC died of sepsis compared with the combined mid/high groups (9.1% vs 0.8%; P < .001). In multivariable analysis, pretransplant ALC was associated with 180-day mortality (hazard ratio, 0.20; P = .004). Patients with low ALC had higher rates of bacteremia (22.7% vs 8.1%; P < .001) and cytomegaloviremia (15.2% vs 6.8%; P = .03) than patients with mid/high ALC. Low ALC pretransplant through postoperative day 30 was associated with 180-day mortality among patients who received rabbit antithymocyte globulin induction (P = .001). Pretransplant lymphopenia is associated with short-term mortality and a higher incidence of posttransplant infections in DDLT patients.

Magnetic resonance three-dimensional steady-state free precession imaging of the thoracic duct in patients with Fontan circulation and its relationship to outcomes

BackgroundLymphatic complications are common in patients with Fontan circulation. Three-dimensional balanced steady-state free precession (3D bSSFP) angiography by cardiovascular magnetic resonance (CMR) is widely used for cardiovascular anatomical assessment. We sought to determine the frequency of thoracic duct (TD) visualization using 3D bSSFP images and assess whether TD characteristics are associated with clinical outcomes. MethodsThis was a retrospective, single-center study of patients with Fontan circulation who underwent CMR. Frequency matching of age at CMR was used to construct a comparison group of patients with repaired tetralogy of Fallot (rTOF). TD characteristics included maximum diameter and a qualitative assessment of tortuosity. Clinical outcomes included protein-losing enteropathy (PLE), plastic bronchitis, listing for heart transplantation, and death. A composite outcome was defined as presence of any of these events. ResultsThe study included 189 Fontan patients (median age 16.1 years, IQR 11.0–23.2 years) and 36 rTOF patients (median age 15.7 years, IQR 11.1–23.7 years). The TD diameter was larger (median 2.50 vs. 1.95 mm, p = 0.002) and more often well visualized (65% vs. 22%, p < 0.001) in Fontan patients vs. rTOF patients. TD dimension increased mildly with age in Fontan patients, R = 0.19, p = 0.01. In Fontan patients, the TD diameter was larger in those with PLE vs. without PLE (age-adjusted mean 4.11 vs. 2.72, p = 0.005), and was more tortuous in those with NYHA class ≥ II vs. class I (moderate or greater tortuosity 75% vs. 28.5%, p = 0.02). Larger TD diameter was associated with a lower ventricular ejection fraction that was independent of age (partial correlation = − 0.22, p = 0.02). More tortuous TDs had a higher end-systolic volume (mean 70.0 mL/m2 vs. 57.3 mL/m2, p = 0.03), lower creatinine (mean 0.61 mg/dL vs. 0.70 mg/dL, p = 0.04), and a higher absolute lymphocyte count (mean 1.80 K cells/µL vs. 0.76 K cells/µL, p = 0.003). The composite outcome was present in 6% of Fontan patients and was not associated with TD diameter (p = 0.50) or tortuosity (p = 0.09). ConclusionsThe TD is well visualized in two-thirds of patients with Fontan circulation on 3D-bSSFP images. Larger TD diameter is associated with PLE and increased TD tortuosity is associated with an NYHA class ≥ II.

Role of pretreatment absolute lymphocyte count in survival outcomes for esophageal cancer treated with neoadjuvant chemoradiotherapy and pembrolizumab: An analysis from a prospective cohort.

338 Background: To analyze the relationship between pre-treatment inflammatory biomarkers (IBs) and survival outcomes for ESCC treated with neo-CRT and pembrolizumab. Methods: Clinical variables and IBs [absolute monocyte count (AMC), absolute lymphocyte count (ALC), platelet count (PLT), neutrophil lymphocyte ratio (NLR), Platelet lymphocyte ratio (PLR), Lymphocyte monocyte ratio (LMR), Pan-Immune Inflammation value (PIV), Systemic immunoinflammatory index (SII), Systemic Immunoreactivity Index (SIRI) and prognostic nutritional index (PNI)] were collected from two prospective trials. Univariate and multivariate analysis was performed. Results: A total of 51 patients were included. Of them, 35 patients achieved pathologic complete response after neo-CRT and pembrolizumab (pCR: 68.6%). With a median follow-up of 20 months, the two-year PFS and OS of the cohort was 64% and 91%, respectively. Multivariate logistic regression analysis indicated that ALC (OR 4.4, p=0.051) and PLT (OR 6.7, p=0.023) were two independent predictors for achieving pCR among ESCC treated with neo-CRT and pembrolizumab. Multivariate Cox regression analysis showed that ALC (HR 0.27, p=0.028) and SIRI (HR 3.13, p=0.048) were two independent predictors for PFS of this patient population. K-M analysis demonstrated that the PFS of ESCC with high base line ALC was significantly better than those with low ALC (2-year PFS: 77% vs. 47%, p=0.027), but not for overall survival (2-year OS: 96% vs. 87%, p=0.46). Conclusions: Our data demonstrates that pre-treatment ALC is an independent predictor for archiving pCR and favorable outcomes of ESCC treated with neo-CRT and pembrolizumab. Clinical trial information: NCT04435197 ; NCT04435197 .[Table: see text]

Prognostic impact of the simple L-index and absolute lymphocyte count early after allogeneic hematopoietic stem cell transplantation

Background aimsThe L-index, designed as a quantitative parameter to simultaneously assess the duration and severity of lymphopenia, and absolute lymphocyte count (ALC) have a prognostic impact after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, discrepancies have been reported in the impact of ALC, and limited information is currently available on the L-index. MethodsTo search for a better clinical tool, the authors retrospectively compared the simple L-index at 30 days (sL-index(30)), which aims to make the original L-index more compact, and ALC at 30 days (ALC(30)) after allo-HSCT in 217 patients who underwent allo-HSCT at the authors’ institutions. ResultsMedian sL-index(30) was 11 712 (range, 4419–18 511) and median ALC(30) was 404 (range, 0–3754). In a multivariate analysis, higher sL-index(30) was associated with a significantly higher cumulative incidence of relapse (CIR) (hazard ratio [HR], 1.01, 95% confidence interval [CI], 1.00–1.02, P = 0.02 for every increase of 100 in sL-index(30)) as well as non-relapse mortality (NRM) (HR, 1.02, 95% CI, 1.00–1.03, P = 0.01 for every increase of 100 in sL-index(30)). Although higher ALC(30) was associated with significantly lower CIR (HR, 0.94, 95% CI, 0.89–1.00, P = 0.04 for every increase of 100/μL in ALC(30)), it was not extracted as an independent risk factor for NRM (HR, 0.96, 95% CI, 0.88–1.05, P = 0.39). Higher sL-index(30) was associated with a slightly higher rate of grade 3–4 acute graft-versus-host disease (GVHD) (HR, 1.02, 95% CI, 1.00–1.04, P = 0.12 for every increase of 100 in sL-index(30)) but not chronic GVHD (HR, 1.00, 95% CI, 0.99–1.01, P = 0.63). ALC(30) was not associated with rates of grade 3–4 acute GVHD (HR, 1.02, 95% CI, 0.88–1.17, P = 0.81) or chronic GVHD (HR, 1.02, 95% CI, 0.98–1.06, P = 0.34). In a receiver operating characteristic curve, the cutoff values of sL-index(30) and ALC(30) for CIR were 9000 and 500, respectively, and the cutoff value of sL-index(30) for NRM was 12 000. ConclusionssL-index(30) is a promising tool that may be applied to various survival outcomes. A large-scale prospective study is needed to clarify whether medical interventions based on sL-index(30) values will improve the clinical prognosis of patients.