Value Of Absolute Lymphocyte Count Research Articles

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

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

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

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

Predictive value of the dynamics of absolute lymphocyte counts for 90-day mortality in ICU sepsis patients: a retrospective big data study

ObjectivesThe objective of the study was to assess the clinical predictive value of the dynamics of absolute lymphocyte count (ALC) for 90-day all-cause mortality in sepsis patients in intensive care...

Abstract PO5-15-03: Neutrophil-lymphocyte ratio and absolute lymphocyte count, inflammatory markers, may predict lymph node metastasis in elderly patients with operable breast cancer

Abstract Background: Blood-derived systemic inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and absolute lymphocyte count (ALC) have been demonstrated as predictive markers of recurrence and prognosis in several malignancies. Increased chronic inflammation with aging has been reported to be involved in cancer cells and their microenvironment. Several studies have also reported a close relationship between inflammatory markers and cancer grade and prognosis in the elderly. In this study, we retrospectively examined the relationship between lymphocyte-related inflammatory markers and prognosis in elderly breast cancer patients. Method: We included 602 patients diagnosed with primary invasive breast cancer at 8 institutions between 2008 and 2013, all of whom were older than 70 years old and had undergone breast cancer surgery. Preoperative blood collection data were used to analyze the relationship between NLR, PLR, LMR, ALC and clinicopathological data including recurrence. Results: The pathological stages of the 602 patients were Stage I: 275, Stage II: 276, and Stage III: 51, with median NLR, PLR, LMR, and ALC values of 2.21, 134.51, 6.76, and 1840, respectively. The mean age of the patients was 75.3 years. The median follow-up was 72.8 months. 76 patients relapsed, and the mean time to relapse was 42.7 months. Lymphocyte-associated inflammatory markers and Li Sheng pathological characteristics showed no significant differences in stage, presence or absence of recurrence, or form of recurrence, but lymph node metastasis on surgical pathology showed significant differences between cases with and without lymph node metastasis in NLR and ALC (P< 0.05). Conclusions: LMR and ALC were considered useful biomarkers that can be easily measured to predict lymph node metastasis in operable elderly breast cancer Citation Format: Emi Tokuda, Midori Morita, Akihiko Shimomura, Yoshiya Horimoto, Yukino Kawamura, Yumiko Ishizuka, Katsutoshi Sekine, Sayaka Obayashi, Yuki Kojima, Toru Higuchi. Neutrophil-lymphocyte ratio and absolute lymphocyte count, inflammatory markers, may predict lymph node metastasis in elderly patients with operable breast cancer [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 PO5-15-03.

Frequency of Dimethyl Fumarate-Induced Lymphopenia among Omani Patients with Multiple Sclerosis.

Dimethyl fumarate (DMF) is known to cause lymphopenia when used to treat patients with multiple sclerosis (MS). However, research on DMF therapy in the Arab world, especially in Oman, is scarce. This study aimed to analyse the prevalence of lymphopenia among Omani patients with MS and their reasons for discontinuing DMF therapy. In this retrospective study, the medical records of Omani patients with MS who were treated using DMF at two tertiary hospitals in Muscat, Oman, from February 2017 to February 2023 were reviewed. Their demographic, clinical and laboratory data were retrieved and analysed. Absolute lymphocyte count values at baseline and at the last follow-up, as well as the reasons for discontinuing DMF therapy, were collected. Descriptive and inferential statistical techniques were used for data analysis. Binary-logistic regression analysis was used to identify the risk factors for DMF-induced lymphopenia. A total of 64 Omani patients with MS were included in this study. The majority of the study participants (n = 40; 63%) were female. All included patients started DMF therapy at the mean age of 33 ± 7.7 years. After administration of DMF, 14 (21.9%) patients developed grades 1-3 of lymphopenia. The DMF therapy was discontinued for 23 (36.0%) patients, mainly in response to adverse events or confirmed pregnancy. Female gender was the only significant predictor of DMF-induced lymphopenia (P = 0.037). Most Omani patients with MS had mild lymphopenia (grades 1-2). Early adverse events and pregnancy were the main reasons provided for discontinuing DMF therapy.

Lymphopenia and spleen dose for patients with inoperable pancreatic cancer receiving ablative 5-fraction radiation therapy.

686 Background: Treatment-induced lymphopenia in pancreatic ductal adenocarcinoma (PDAC) patients after radiation therapy (RT) may negatively impact overall survival (OS). While non-ablative RT (NA-RT) is routine for borderline resectable (BRPC) and locally advanced (LAPC) PDAC, ablative RT (A-RT) has garnered increasing interest based on data suggesting improved clinical outcomes including OS. Absolute lymphocyte count (ALC) changes after A-RT and the potential association with spleen dose in this setting have not been previously described. Methods: We performed a single-institution retrospective analysis of BRPC, LAPC, and medically inoperable PDAC patients to evaluate ALC values 1 month before vs. 1-3 months after A-RT. All were treated with 5-fraction A-RT on a 0.35 T MR-Linac; the spleen was not considered an organ-at-risk during treatment planning. Lymphopenia was assessed using CTCAE version 5.0. Results: 101 patients were evaluated with median age 71 years (range 35-94 years), median maximum tumor size of 3.6 cm (range, 1.3-6.8 cm), and frequently tumor in the pancreas head (84.2%). Most had LAPC (61.4%) followed by BRPC (28.7%). Induction chemotherapy (ICT) was routine (89.1%), most commonly FOLFIRINOX (61.4%) with a median ICT duration of 5.2 months (range, 0.2-14.0 months). Median prescribed dose was 50 Gy (range, 40-50 Gy). The median mean spleen dose was 2.75 Gy (range, 0.38-16.79 Gy). The median spleen V5Gy, V10Gy, V15Gy, and V20Gy were 12.8% (range, 0 - 77.5%), 1.9% (range, 0 - 66.2%), 0% (range, 0 - 54.5%), and 0% (range, 0 - 39.2%), respectively. The median ALC at a median 25.5 days before A-RT was 1.39 no./mL (range, 0.24 - 3.00 no./mL), and this decreased to 0.85 no./mL (range, 0.20-2.45 no./mL) a median 6 weeks after A-RT. Grade 2 lymphopenia (G2L) prior to vs. after A-RT was 6.9% vs. 27.7% (p<0.001). Grade 3 lymphopenia (G3L) prior to vs. after A-RT was 1.0% vs. 13.9% (p<0.001). No grade 4+ lymphopenia was observed. Significant factors on multivariable analysis (MVA) for G2L were age (OR: 1.05, 95% CI 1.01-1.09, p=0.019), male vs. female (OR: 0.30, 95% CI:0.11-0.82, p=0.019), and T1-3 vs. T4 (OR: 0.27, 95% CI: 0.10-0.71, p=0.007); ICT duration, target volume dose/volume, and spleen dose were not significant on univariate analysis (UVA). No factors were significant on UVA for G3L, but a trend was observed for T1-3 vs. T4 (OR: 3.5, 95% CI: 0.91-13.42, p=0.067) and spleen V5Gy (OR: 1.44, 95% CI: 0.85-3.26, p=0.065). Conclusions: To our knowledge, this is the first study to evaluate spleen dose and ALC changes after A-RT for PDAC. We observed a similar incidence of grade 2+ lymphopenia compared to prior 5-fraction NA-RT studies. There was a trend towards significance of higher spleen V5Gy being associated with a higher probability of G3L. We are evaluating whether grade 2+ lymphopenia is associated with long-term clinical outcomes after A-RT for inoperable PDAC.

Abstract A004: Lymphopenia and spleen dose for inoperable pancreatic cancer patients receiving ablative 5-fraction radiation therapy

Abstract Background: Treatment-induced lymphopenia in pancreatic ductal adenocarcinoma (PDAC) patients after radiation therapy (RT) may negatively impact overall survival (OS). While non-ablative RT (NA-RT) is routine for borderline resectable (BRPC) and locally advanced (LAPC) PDAC, ablative RT (A-RT) has garnered increasing interest based on data suggesting improved clinical outcomes including OS. Absolute lymphocyte count (ALC) changes after A-RT and the potential association with spleen dose in this setting have not been previously described. Methods: We performed a single-institution retrospective analysis of BRPC, LAPC, and medically inoperable PDAC patients to evaluate ALC values 1 month before vs. 1-3 months after A-RT and evaluate their association with patient outcomes. All patients were treated with 5-fraction A-RT on a 0.35 T MR-Linac using step-and-shoot IMRT with ~15-20 fields; the spleen was not considered an organ-at-risk during treatment planning. Lymphopenia was assessed using CTCAE version 5.0. Results: 101 patients were evaluated with median age 71 years (range 35-94 years), median maximum tumor size of 3.6 cm (range, 1.3-6.8 cm), and frequently tumor in the pancreas head (84.2%). Most had LAPC (61.4%) followed by BRPC (28.7%). Induction chemotherapy (ICT) was routine (89.1%), most commonly FOLFIRINOX (61.4%) with a median ICT duration of 5.2 months (range, 0.2-14.0 months). Median prescribed dose was 50 Gy (range, 40-50 Gy). The median mean spleen dose was 2.75 Gy (range, 0.38-16.79 Gy). The median spleen V5Gy, V10Gy, V15Gy, and V20Gy were 12.8% (range, 0 - 77.5%), 1.9% (range, 0 - 66.2%), 0% (range, 0 - 54.5%), and 0% (range, 0 - 39.2%), respectively. [KEM1] The median ALC at a median 25.5 days before A-RT was 1.39 no./mL (range, 0.24 - 3.00 no./mL), and this decreased to 0.85 no./mL (range, 0.20-2.45 no./mL) a median 6 weeks after A-RT[MH2]. Grade 2 lymphopenia (G2L) prior to vs. after A-RT was 6.9% vs. 27.7% (p<0.001). Grade 3 lymphopenia (G3L) prior to vs. after A-RT was 1.0% vs. 13.9% (p<0.001). No grade 4+ lymphopenia was observed. Significant factors on multivariable analysis (MVA) for G2L were age (OR: 1.05, 95% CI 1.01-1.09, p=0.019), male vs. female (OR: 0.30, 95% CI:0.11-0.82, p=0.019), and T1-3 vs. T4 (OR: 0.27, 95% CI: 0.10-0.71, p=0.007); ICT duration, target volume dose/volume, and spleen dose were not significant on univariate analysis (UVA). No factors were significant on UVA for G3L, but a trend was observed for T1-3 vs. T4 (OR[MH3] : 3.5, 95% CI: 0.91-13.42, p=0.067) and spleen V5Gy (OR: 1.44, 95% CI: 0.85-3.26, p=0.065). Discussion: To our knowledge, this is the first study to evaluate spleen dose and ALC changes after A-RT for PDAC. We observed a similar incidence of grade 2+ lymphopenia compared to prior 5-fraction NA-RT studies. There was a trend towards significance of higher spleen V5Gy being associated with a higher probability of G3L. We are currently evaluating whether grade 2+ lymphopenia is associated with long-term clinical outcomes after A-RT for inoperable PDAC. Citation Format: Michael D. Chuong, Roberto Herrera, Nicolas Carvallo, Muni Rubens, Rupesh Kotecha, Matthew D. Hall, Kathryn E. Mittauer, Nema Bassiri-Gharb, Alonso N. Gutierrez, Adeel Kaiser. Lymphopenia and spleen dose for inoperable pancreatic cancer patients receiving ablative 5-fraction radiation therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A004.

Outcomes of Antithymocyte Globulin and Cyclosporine for Severe Aplastic Anemia

Background: Aplastic anemia (AA) is mediated by T cell destruction of hematopoietic stem and progenitor cells causing pancytopenia and bone marrow hypoplasia. The current standard of care for severe aplastic anemia (SAA) is hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST) with antithymocyte globulin (ATG) plus cyclosporine (CsA) with or without eltrombopag (Epag), a thrombopoietin receptor agonist. HSCT is preferred for SAA in young adults as a curative option, but only a small proportion of patients have histocompatible siblings and mortality increases with age. The IST plus CsA combination with or without Epag has led to survival rates comparable with those observed with HSCT recipients. However, complete hematologic remission is rare with IST and there is a considerable risk of clonal complications, including PNH evolution and progression to MDS. The aim of this study was to evaluate outcomes of ATG plus CsA therapy in a large cohort of SAA patients. Methods: We retrospectively analyzed medical records of 156 patients with SAA, aged ≥2 years treated with ATG plus CsA with or without Epag at our institution between July 2000 and January 2023. Hematologic responses were evaluated at 3-, 6- and 12-months post therapy initiation. Super response (SR) was defined as hemoglobin ≥12 g/dL, platelet count ≥150x10 9/L and absolute neutrophil count (ANC) ≥1.0x10 9/L; complete response (CR) was defined as hemoglobin ≥10 g/dL, platelet count ≥100x10 9/L and ANC ≥1.0x10 9/L. Partial response (PR) was defined as not meeting the criteria for CR and SAA. Overall response encompassed SR, CR, and PR. Statistical analyses were performed with the use of Chi-squared test and Kaplan Meier method. Results: The median age at diagnosis was 52 (IQR 30-66) years, 47% were male, and 86% were Caucasian. Twenty three percent of the cohort had coexisting paroxysmal nocturnal hemoglobinuria. Most patients were treated with ATG plus CsA (92%), the remaining 8% additionally received Epag. Overall response rates were 70%, 67%, and 77% at 3-, 6- and 12-months post-treatment initiation, respectively. CR was achieved in 10%, 15%, and 18% at 3-, 6- and 12-months, respectively. SR was achieved in 16.3% of patients at 12 months, as shown in Figure 1. Patients who achieved SR were young with median age at diagnosis of 28 years, while those who achieved PR or no response had a median age of 54 and 56 years, respectively. Patients who responded to the ATG + CsA therapy had significantly higher baseline ANC (p=0.04), absolute reticulocyte count (ARC) (p<0.001) and absolute lymphocyte count (ALC) (p<0.001). Pre-treatment median values of ANC, ARC and ALC were higher for patients who achieved SR compared to the rest of responders. With a median follow up time of 4.5 years, the estimated median relapse free survival was 9.2 years (95% CI, 3.2 - not reached [NR]) (Figure 2). Of the entire cohort, 21 (13%) patients progressed to acute myeloid leukemia or myelodysplastic syndrome. At data cut off, a total of 66 patients had died; the estimated median OS was 11.6 years (95% CI, 8.4 - NR). In particular, 30 patients died within the first 12-months, 13 within 3-months of ATG initiation from treatment-related complications, 6 from pneumonia and the rest from unknown causes. Conclusion: The findings of our study demonstrate that ATG plus CsA is an effective and safe treatment option for patients with SAA, especially in the older patient population where HSCT-related toxicities can lead to high mortality. Those with higher baseline ALC, ANC and ARC were more likely to respond to therapy compared to those with lower counts. A small percentage of patients progressed to myeloid neoplasia. Mortality within the first 12-months was high, indicating the need for close monitoring to avoid treatment-related mortality.

Risk of on-treatment lymphopenia is associated with treatment outcome and efficacy of consolidation immunotherapy in patients with non-small cell lung cancer treated with concurrent chemoradiotherapy

Background and purposeThe ability of the effective dose to immune cells (EDIC) and the pre-radiotherapy (RT) absolute lymphocyte count (ALC) to predict lymphopenia during RT, treatment outcomes, and efficacy of consolidation immunotherapy in patients with locally advanced non-small cell lung cancer was investigated. Methods and materialsAmong 517 patients treated with concurrent chemoradiotherapy, EDIC was calculated using the mean doses to the lungs, heart, and total body. The patients were grouped according to high and low EDIC and pre-RT ALC, and the correlations with radiation-induced lymphopenia and survival outcomes were determined. ResultsAltogether, 195 patients (37.7%) received consolidation immunotherapy. The cutoff values of EDIC and pre-RT ALC for predicting severe lymphopenia were 2.89 Gy and 2.03 × 109 cells/L, respectively. The high-risk group was defined as EDIC ≥ 2.89 Gy and pre-RT ALC < 2.03 × 109 cells/L, while the low-risk group as EDIC < 2.89 Gy and pre-RT ALC ≥ 2.03 × 109 cells/L, and the rest of the patients as the intermediate-risk group. The incidences of severe lymphopenia during RT in the high-, intermediate-, and low-risk groups were 90.1%, 77.1%, and 52.3%, respectively (P < 0.001). The risk groups could independently predict both progression-free (P < 0.001) and overall survival (P < 0.001). The high-risk group showed a higher incidence of locoregional and distant recurrence (P < 0.001). Consolidation immunotherapy showed significant survival benefit in the low- and intermediate-risk groups but not in the high-risk group. ConclusionsThe combination of EDIC and pre-RT ALC predicted severe lymphopenia, recurrence, and survival. It may potentially serve as a biomarker for consolidation immunotherapy.

Prediction of Lymphopenia and Survival with Baseline Absolute Lymphocyte Count and Irradiated Dose to Immune Cells in Patients with Non-Small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy

This study aimed to investigate the effect of effective dose to immune cell (EDIC) combined with pre-radiotherapy (RT) absolute lymphocyte count (ALC) on treatment-related lymphopenia during RT and treatment outcome in patients with locally advanced non-small cell lung cancer (NSCLC). A subgroup analysis in patients who received consolidation immunotherapy was also conducted. Between August 2008 and December 2021, 517 patients with locally advanced NSCLC treated with definitive concurrent chemoradiotherapy (CRT) were retrospectively analyzed. All patients had serial complete-blood-count tests at pre-, and during-CRT. Severe lymphopenia was defined as ALC < 0.5x109cells/L during RT. EDIC was calculated according to mean doses of the lung, heart and the total body. The patients were grouped according to high and low EDIC and pre-RT ALC and was assessed for its correlation with radiation induced lymphopenia and survival outcomes. Of 517 eligible patients, most of the patients received weekly paclitaxel with carboplatin (90.3%) and 195 patients (37.7%) received consolidation immunotherapy following CRT. A median radiation dose of 63 Gy (IQR, 60-64.5) was delivered in 30 fractions. The optimal cutoff value of EDIC and pre-RT ALC for predicting severe lymphopenia were 2.89 Gy and 2.03x109cells/L, respectively. High risk group was defined as EDIC ≥ 2.89 Gy and pre-RT ALC < 2.03x109cells/L, low risk group as EDIC <2.89 Gy and pre-RT ALC ≥ 2.03x109cells/L, and intermediate group as EDIC ≥ 2.89 Gy and pre-RT ALC ≥ 2.03x109cells/L or EDIC < 2.89 Gy and pre-RT ALC < 2.03x109cells/L. The incidence of severe lymphopenia during RT in high, intermediate, and low risk group was 90.1%, 77.1%, and 52.3%, respectively (p<0.001). The risk groups were independent predictors for both progression-free survival (PFS) (p<0.001) and overall survival (OS) (p<0.001). The high-risk group had higher incidence of locoregional and distant recurrences (p<0.001). In the subset of patients who were treated with consolidation immunotherapy, the risk groups were predictive of severe lymphopenia (p = 0.001), PFS (p = 0.004), and OS (p = 0.012). This study demonstrated that the combination of EDIC and pre-RT ALC is a predictor for severe lymphopenia during RT, recurrence, and survival in patients with locally advanced NSCLC who received CRT. Moreover, the combination of EDIC and pre-RT ALC may serve as a potential biomarker for the benefit of maintenance immunotherapy.

Prognostic value of absolute lymphocyte count in oral cavity squamous cell carcinoma.

Absolute lymphocyte count (ALC) has been shown to be a prognostic indicator in other solid tumors. Given this, we aimed to evaluate the prognostic value of ALC in oral cavity squamous cell carcinoma (OSCC). Using our institutional tumor registry data, we identified patients ≥18 years old who were diagnosed with OSCC between 2012 and 2018. Preoperative ALC values within 30 days of surgery were collected through retrospective chart review. American Joint Committee on Cancer, 7th-edition best stage was used to categorize cancers as early stage (stages 1 and 2) or late-stage (stages 3 and 4). Primary outcomes were likelihood of recurrence and survival rates after 3 years. Of the 412 patients identified, 262 patients had available ALC data and met inclusion criteria. Early stage cancer patients who had lymphopenia did not have any significant difference in their rate of death ([OR], 1.71, CI: 0.54-5.45, p = .36) or likelihood recurrence ([OR], 0.60, CI: 0.06-5.87, p = .66) after controlling for age, tobacco use, alcohol use, positive margins, and adjuvant therapy. Late-stage cancer patients who had lymphopenia also showed no difference in their rate of death ([OR], 2.74, CI: 0.65-11.6, p = .17) or likelihood of recurrence ([OR], 0.38, CI: 0.04-3.36, p = .38). This study evaluates the prognostic value of ALC in oral cavity cancers. Our findings demonstrate that pretreatment ALC is not significantly associated with recurrence and survival outcomes patients with OSCC. III. Absolute lymphocyte count (ALC) has been associated with prognosis in several cancers. We found that preoperative ALC was not associated with likelihood of survival or recurrence in patients with early stage or late-stage oral cavity cancer.

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.

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.

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.

Predictive role of absolute lymphocyte count in daratumumab-treated patients with relapsed/ refractory multiple myeloma.

Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.

Macrophage activation syndrome in children with Kikuchi-Fujimoto disease

BackgroundKikuchi-Fujimoto disease (KFD) is typically a benign, self-limiting inflammatory disease. However, some patients may have a prolonged or recurrent disease course, or present with life-threatening complications such as macrophage activation syndrome (MAS). In this study, we aimed to describe the incidence and clinical features of MAS in KFD and to access potential laboratory markers for the diagnosis of KFD-associated MAS.MethodsPatients with KFD were retrospectively enrolled from January 2015 to November 2021 at Shenzhen Children’s Hospital. Clinical data were collected from inpatient or outpatient medical records. Data collected included clinical manifestations, laboratory and imaging findings, treatment, and clinical outcomes. Data were analyzed using GraphPad Prism 8.0 statistical software (GraphPad Software Inc., La Jolla, CA, USA). A receiver operating characteristic (ROC) curve analysis was further performed to access the potential predictors for the KFD-MAS diagnosis.ResultsOf 58 patients with a histological diagnosis of KFD, 15 (25.9%) patients had MAS. Compared to patients without MAS, patients with KFD-MAS presented with a higher proportion of skin rash (26.7%, p = 0.01), glucocorticoid treatment (80%, p = 0.003), and disease recurrence (33.3%, p = 0.04). KFD-MAS patients had lower absolute peripheral white blood cell (WBC, p = 0.02), platelet (p = 0.002), serum albumin levels (p = 0.01), and lymphocyte count (p < 0.0001), and higher lactate dehydrogenase (LDH) levels (p < 0.0001). ROC curve analysis showed that the cutoff values of absolute lymphocyte count, an absolute platelet count, serum albumin level, and serum LDH level for KFD-MAS diagnosis were < 1235/μL, < 171 × 106/μL, < 35.6 g/L, and > 679 IU/mL, respectively.ConclusionsThe presence of KFD-MAS in children may be more common than previously expected, especially in those with skin rash. KFD-MAS may be associated with a higher recurrence rate. An extremely elevated serum LDH level and moderate to severe lymphopenia may be useful diagnostic markers for MAS in KFD.Trial registrationNot applicable; this was a retrospective study.

Absolute Lymphocyte Count Changes During Neoadjuvant Chemotherapy are Associated With Prognosis of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Patients

ntroduction/BackgroundSome reports have shown that absolute lymphocyte count (ALC) is associated with prognosis in breast cancer; however, the impact of ALC changes remains unclear. This study aimed to investigate the relationship between ALC changes during neoadjuvant chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients and disease prognosis. Patients and MethodsThis retrospective cohort study January 2010 to September 2020) included patients diagnosed with HER2-positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy. The ALC ratio was defined as the ALC value after administration of the anti-HER2 drug divided by the ALC value before administration. The optimal ALC ratio cut-off value was identified using the receiver operating characteristic curve analysis and Youden's index. The relationship between the ALC ratio and disease-free survival was assessed using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. ResultsData from a total of 100 HER2-positive breast cancer patients were analyzed. The cut-off value of the ALC ratio was set as 1.142. The median follow-up period was 52.0 (range: 5.1-123.7) months. The 5-year disease-free survival rates were 88.4% and 60.9% in the high-and low-ALC ratio groups, respectively, and were significantly higher in the high-ALC ratio group (p = .0031). The ALC ratio was an independent prognostic factor in multivariate Cox proportional hazards analysis (p = .0032). ConclusionHER2-positive breast cancer patients with a higher ALC ratio during trastuzumab-based neoadjuvant chemotherapy may have a better prognosis than their counterparts.

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.