Higher Absolute Lymphocyte Count Research Articles

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.

Clinical verification of the relationship between serum lipid metabolism and immune activity in breast cancer patients treated with neoadjuvant chemotherapy

BackgroundLipid metabolism has been recently reported to affect the prognosis and tumor immune activity in cancer patients. However, the effect of lipid metabolism on chemosensitivity in patients with breast cancer treated with neoadjuvant chemotherapy (NAC) remains unclear.MethodsWe examined 327 patients with breast cancer who were treated with NAC followed by curative surgery. The correlations between the serum levels of total cholesterol (TC) and triglyceride (TG) and the clinicopathological features, including the efficacy of NAC, neutrophil-to-lymphocyte ratio (NLR), and absolute lymphocyte count (ALC), were evaluated retrospectively.ResultsSerum TG levels were increased after NAC in all the subtypes, and the rate of change was the highest, especially in triple-negative breast cancer (TNBC) (21.0% → 48.1%). In addition, only TNBC patients with an objective response (OR) had significantly higher TG levels after NAC than those without (P = 0.049). Patients with a high ALC before NAC had significantly higher TG levels after NAC than patients with all breast cancer (P = 0.001), HER2-enriched breast cancer (P = 0.021), and TNBC (P = 0.008). Patients with a low NLR before NAC had significantly higher TG levels after NAC only among patients with TNBC (P = 0.025). In patients with human epidermal growth factor receptor 2-enriched breast cancer, the group with normal TC levels before NAC had significantly better OS than those with high TC levels (P = 0.013, log-rank test), and in patients with TNBC, the group with high TC levels after NAC had significantly better OS than those with normal TC levels (P = 0.014, log-rank test).ConclusionsGood systemic immune activity and chemosensitivity may be associated with lipid metabolism regulated by NAC in TNBC patients.

A composite score for predicting vertical transmission of hepatitis C: a multicenter study

Prevention of vertical transmission of hepatitis C virus (HCV) presents an obstetric challenge. We aimed to create a composite score to accurately isolate a population of pregnant women with HCV who will have a high rate of vertical transmission. In a retrospective, multicenter, cohort study, we identified pregnant women 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 history, infectious history, liver function tests, HCV RNA titer, HCV antibody, HCV genotype, absolute lymphocyte count, and platelet count were collected. Data were analyzed by logistic regression and receiver operating characteristic (ROC). We identified 157 pregnant women and 163 corresponding infants. The median maternal delivery age was 29 (IQR: 25-33) years, and the majority (141 or 89.8%) were white, high HCV RNA titer, high absolute lymphocyte count and high platelet count were associated with vertical transmission. A composite score combining the three risk factors ha an AUROC of 0.934 (95% CI= 0.883-0.985), superior to any of the three risk factors individually. The sensitivity, specificity and positive predictive value were 100.0%, 86.4%, and 42.9%, respectively. A composite score combining risk factors HCV vertical transmission can isolate a population of pregnant women where the rate of vertical transmission is high, allowing for potential interventions during antepartum or intrapartum care.

CD34+ Cell Mobilization, Autograft Cellular Composition and Outcome in Mantle Cell Lymphoma Patients

Backgound: Autologous stem cell transplantation (ASCT) is a standard treatment in transplant-eligible mantle cell lymphoma (MCL) patients after first-line chemoimmunotherapy. Study Design and Methods: This prospective multicenter study evaluated the impact of CD34+ cell mobilization and graft cellular composition analyzed by flow cytometry on hematologic recovery and outcome in 42 MCL patients. Results: During CD34+ cell mobilization, a higher blood CD34+ cell count (>30 × 106/L) was associated with improved overall survival (median not reached [NR] vs. 57 months, p = 0.04). The use of plerixafor did not impact outcome. Higher number of viable cryopreserved graft CD34+ cells (>3.0 × 106/kg) was associated with faster platelet (median 11 vs. 15 days, p = 0.03) and neutrophil (median 9 vs. 10 days, p = 0.02) recovery posttransplant. Very low graft CD3+CD8+ cell count (≤10 × 106/kg) correlated with worse progression-free survival (PFS) (HR 4.136, 95% CI 1.547–11.059, p = 0.005). On the other hand, higher absolute lymphocyte count >2.5 × 109/L at 30 days after ASCT (ALC-30) was linked with better PFS (median NR vs. 99 months, p = 0.045) and overall survival (median NR in either group, p = 0.05). Conclusions: Better mobilization capacity and higher graft CD3+CD8+ cell count had a positive prognostic impact in this study, in addition to earlier lymphocyte recovery (ALC-30>2.5 × 106/L). These results need to be validated in another study with a larger patient cohort.

Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The U.S. Myeloma CAR T Consortium Real World Experience

Introduction: Chimeric Antigen Cell (CAR) T-cell therapy with idecabtagene vicleucel (ide-cel) is FDA approved for relapsed refractory multiple myeloma (MM). Investigating factors that may predict response, toxicity and survival is important to guide therapy and inform prognosis. Low pre-lymphodepletion (LD) absolute lymphocyte count (ALC) was found to be associated with worse outcomes in a small cohort of patients (pts) treated with ide-cel (Liu et al. Transplant Cell Ther 2022). We evaluated the impact of pre-apheresis (pre-A) and pre-LD peripheral blood ALC on post-ide-cel outcomes in a large patient cohort. Methods: A total of 215 myeloma pts were treated with ide-cel at 11 U.S. academic medical centers. We studied the effect of ALC including pre-A, pre-LD, absolute and percent reduction in ALC between apheresis and LD on progression free survival (PFS), overall survival (OS), overall hematologic response rate (ORR which included VGPR, CR and sCR) and cytokine release syndrome (CRS) incidence. Associations of ALC parameters with PFS and OS were evaluated using Kaplan-Meier (KM) method and Cox proportional hazard model. Patient demographics and clinical characteristics between ALC groups were compared using Chi square test and Wilcoxon rank test. Results: The median patient age was 64 years (range, 36-83) and 60 % were male. The median prior lines of therapy was 6 (IQR, 5-9), 84.2% had a prior autologous hematopoietic cell transplant (AHCT), 44.7% had extramedullary disease, and 77.1% received bridging therapy (BT). CRS was seen in 81.1% of the pts, mostly grade 1. The median pre-A and pre-LD ALC's were 0.65 x109/L (range, 0.06-5.3) and 0.55 (range, 0-5.0), respectively. The pre-A ALC was significantly higher than pre-LD ALC (mean difference and 95% CI: 0.10 (0.04, 0.40), p=0.002). The median follow-up time after CAR-T infusion was 5.4 (IQR, 2.1-8.3) months. Pre-A and pre-LD ALC's were not significantly associated with PFS or OS, while pts with a high absolute reduction in ALC between apheresis and LD (≥0.27 or top quartile) had a significantly worse six-month PFS (48.4 vs 63.5%, p= 0.04) and OS (76.0 vs 87.7%, p= 0.03). Similarly, patients with a high percent reduction between pre-A and pre-LD ALC (≥37.5% or top quartile) had a worse six-month PFS (41.9 vs 65%, p <0.001) and OS (70.5 vs 89%, P=0.001). PFS and OS differences remained statistically significant after adjusting for age, race, CRS grade, ECOG-PS, extramedullary disease and prior AHCT. Kaplan-Meier estimated PFS and OS curves for absolute ALC reduction groups and percent ALC reduction groups are displayed in Figure 1. The one-month and three-month ORR, and CRS grade were not significantly different between pre-A (≥1 or <1), pre-LD (≥1 or <1), absolute reduction and percent reduction ALC groups. ECOG-PS ≥2 (p= 0.004), ISS III (p= 0.015), and implementation of BT (p <0.01) were found to be associated with high ALC reduction or percent reduction. There was no difference in ALC between pts who received BT vs not. However, more patients in the high ALC reduction (>=0.27: 90.4% vs 72.6%, p=0.008) and high ALC percent reduction (>=37.5: 96.2% vs 70.5%) groups received BT. Moreover, pts who received BT had a worse PFS (six-month PFS: 53.2% vs 85.3%, p <0.001) and OS (six-month OS: 81.9% vs 95.8%, p= 0.02) likely indicating aggressive disease biology. The specific types of BT were not available in our dataset. Conclusion: Pre-apheresis ALC did not impact survival in this large cohort of myeloma patients treated with ide-cel. Reduction in ALC between apheresis and lymphodepletion is a potentially predictive tool of survival outcomes and may be associated with more aggressive disease biology and the need for more aggressive bridging therapy. Investigating the association between specific types of bridging therapy, ALC reduction and outcomes may guide clinical decision making in this heavily pretreated myeloma patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Red Cell Distribution Width and Absolute Lymphocyte Count Associate With Biomarkers of Inflammation and Subsequent Mortality in Rheumatoid Arthritis.

Morbidity and mortality in rheumatoid arthritis (RA) is partly mitigated by maintaining immune and hematologic homeostasis. Identification of those at risk is challenging. Red cell distribution width (RDW) and absolute lymphocyte count (ALC) associate with cardiovascular disease (CVD) and mortality in the general population, and with disease activity in RA. How these variables relate to inflammation and mortality in RA was investigated. In a retrospective single Veterans Affairs (VA) Rheumatology Clinic cohort of 327 patients with RA treated with methotrexate (MTX)+/- a tumor necrosis factor (TNF) inhibitor (TNFi), we evaluated RDW and ALC before and during therapy and in relation to subsequent mortality. Findings were validated in a national VA cohort (n = 13,914). In a subset of patients and controls, we evaluated inflammatory markers. In the local cohort, high RDW and low ALC prior to MTX treatment was associated with subsequent mortality over 10 years (both P < 0.001). The highest mortality was observed in those with both high RDW and low ALC. This remained after adjusting for age and comorbidities and was validated in the national RA cohort. In the immunology cohort, soluble and cellular inflammatory markers were higher in patients with RA than in controls. ALC correlated with age, plasma TNF receptor II, natural killer HLA-DR mean fluorescence intensity, and CD4CM/CD8CM HLA-DR/CD38%, whereas RDW associated with age and ALC. MTX initiation was followed by an increase in RDW and a decrease in ALC. TNFi therapy added to MTX resulted in an increase in ALC. RDW and ALC before disease-modifying antirheumatic drug therapy are associated with biomarkers of monocyte/macrophage inflammation and subsequent mortality. The mechanistic linkage between TNF signaling and lymphopenia found here warrants further investigation.

S1604 Prognostic Value of Systemic Inflammatory Markers in Gastric MALT Lymphoma

Introduction: Several studies have shown the role of inflammatory markers, especially the neutrophil-to-lymphocyte Ratio (NLR), as indicators of poor prognosis in various gastrointestinal malignancies. We aimed to examine the prognostic value of NLR, among other markers, and their relationship with the presence of baseline distant metastasis in patients with MALT Lymphoma. Methods: We retrospectively reviewed the charts of 139 patients with Gastric MALT Lymphoma treated at a tertiary care cancer center from 2012 to 2018. We examined the relationship between absolute eosinophilic count (AEC), absolute lymphocyte count (ALC), absolute monocytic count (AMC), absolute neutrophil count (ANC), monocyte to lymphocyte ratio (MLR), NLR, and platelet to lymphocyte ratio (PLR) with the presence distant metastases, and overall survival (OS). We used multivariable logistic regression analyses to test the association between the variables and the presence of baseline distant metastases. Results: The median age was 55 years, and males comprised 67.6% of the patients. The ROC value of 3.4 was determined as the cutoff value for NLR. High NLR (NLR > 3.4 µL) was significantly associated with the presence of distant metastasis at diagnosis (P-value, 0.02, Odds Ratio (OR): 2.4, CI: 1.14- 5.10). High ALC ( >1819) was also associated with the presence of baseline distant metastasis (P-value, 0.04, OR: 0.46, CI: 0.22- 0.98). Multivariable analysis showed that high NLR (P-value, 0.02, OR 2.4 95% CI 1.1-5.1) was an independent risk factor for distant metastasis at presentation (Figure). High ANC, NLR, and PLR, were associated with poor OS, (P-value, 0.027, 0.016, and 0.011 respectively). Conclusion: High systemic inflammatory markers are associated with poor prognosis (the presence of distant metastasis) and poor OS in patients with Gastric MALT Lymphoma. To our knowledge, this is the first study examining the association between these inflammatory markers and the presence of distant metastases in MALT Lymphoma. Whether these markers could predict the response to treatment is unknown (Table).Figure 1.: (Top)Kaplan Meier curve for overall survival of patients with ANC (Middle). Kaplan Meier curve for overall survival of patients with NLR (Bottom). Kaplan Meier curve for overall survival of patients with PLR Table 1. - The association between systemic inflammatory markers and overall survival Parameter Median OS P-value Hazard Ratio 95% Confidence Interval ANC >5100 6.4 months 0.027 1.5 1.04–2.1 ANC≤5100 10.9 months ALC >1819 7.6 months 0.19 0.80 0.55–1.1 ALC≤1819 6.7 months AMC > 603 6.3 months 0.66 1.1 0.76–1.6 AMC≤ 603 7.8 months NLR > 2.75 6.2 months 0.016 1.5 1.1–2.2 NLR ≤ 2.75 12.2 months MLR >0.32 6.3 months 0.36 1.2 0.83–1.7 MLR≤0.32 10.5 months PLR >0.16 6.2 months 0.011 1.6 1.1–2.3 PLR≤0.16 10.9 months

S20 Prognostic Value of Systemic Inflammatory Markers in Patients With Pancreatic Adenocarcinoma

Introduction: Several studies have shown the role of inflammatory markers, especially the neutrophil-to-lymphocyte ratio (NLR), as indicators of poor prognosis in various gastrointestinal malignancies. We aimed to examine the prognostic value of NLR, among other markers, and their relationship with the presence of baseline distant metastasis in patients with pancreatic adenocarcinoma. Methods: We retrospectively reviewed the charts of 355 patients with pancreatic cancer treated at a tertiary cancer center from 2013 to 2018. We examined the relationship between absolute eosinophilic count (AEC), absolute lymphocyte count (ALC), absolute monocytic count (AMC), absolute neutrophil count (ANC), monocyte to lymphocyte ratio (MLR), NLR, and platelet to lymphocyte ratio (PLR) with the presence distant metastases, and overall survival (OS). We used multivariable logistic regression analyses to test the association between the variables and the presence of baseline distant metastases. Results: The median age was 60 years, and males comprised 59% of the patients. The ROC value of 3.3 was determined as the cutoff value for NLR. High NLR (NLR >3.3 µL) was significantly associated with the presence of distant metastasis at diagnosis (P-value < 0.0001, Odds Ratio (OR): 1.7, CI: 2.6–4.0). High baseline ANC (≥5500/μL), high AMC (≥600/μL), and high MLR (≥0.3) were also associated with baseline distant metastases (P-value: 0.02, 0.001, and <0.0001 respectively). Multivariable analysis showed that high NLR (P-value, 0.0003, OR 2.5 95% CI 1.5–4.1) was an independent risk factor for distant metastasis at presentation. High ANC, NLR, MLR, and PLR and low ALC were associated with poor OS (P-value: <0.0001, <0.0001, <0.0001, 0.04, and 0.01, respectively) (Figure 1). Conclusion: High systemic inflammatory markers are associated with poor prognosis (the presence of distant metastasis) and poor OS in patients with pancreatic cancer. Simple laboratory tests such as complete blood counts can be used as markers of poor prognosis and poor OS in patients with pancreatic cancer (Table 1). Table 1. - The association between systemic inflammatory markers with the presence of distant metastases Baseline distant metastases Present Absent p- value Odds Ratio 95% Confidence Interval ANC≥5500 113 (64%) 63 (36%) 0.024 1.65 (1.0-2.5) ANC< 5500 92 (52%) 85 (48%) ALC≥1680 99 (57%) 75 (43%) 0.65 0.9 (0.6-1.4) ALC< 1680 106 (59%) 73 (41%) AMC≥ 600 117 (66%) 59 (34%) 0.001 2.0 (1.3-3.0) AMC< 600 88 (50%) 89 (50%) AEC≥ 143 83 (62%) 51 (38%) 0.38 1.2 (0.7-2.0) AEC< 143 76(57%) 58 (43%) NLR≥3.3 126 (69%) 56 (31%) < .0001 2.6 (1.7-4.0) NLR< 3.3 79 (46%) 92 (54%) MLR≥0.3 130 (68%) 62 (32%) < .0001 2.4 (1.5-3.7) MLR< 0.3 75 (46%) 86 (54%) PLR≥0.15 108 (61%) 68 (39%) 0.2 1.3 (0.85-2.0) PLR< 0.15 97 (55%) 80 (45%) Figure 1.: Kaplan Meier curve for overall survival with NLRFigure 2.: Kaplan Meier curve for overall survival with ANCFigure 3.: Kaplan Meier curve for overall survival with ALC

Absolute lymphocyte count decreases with disease progression and is a potential prognostic marker for metastatic breast cancer.

Peripheral blood parameters such as the neutrophil-to-lymphocyte ratio (NLR) are prognostic markers for breast cancer patients. For instance, patients with a high NLR have a poor prognosis. Meanwhile, high absolute lymphocyte count (ALC) is reportedly a predictive factor for some chemotherapies. However, the underlying mechanisms behind how these markers relate to patient outcomes and how these markers change during the clinical course of patients with metastatic breast cancer (MBC) remains unknown. We retrospectively investigated 156 patients who were treated for MBC and eventually transitioned to best supportive care (BSC) at our hospital between January 2017 and December 2021. Changes in peripheral blood parameters during MBC treatments and their association with patient outcomes were examined. From the time of MBC diagnosis (baseline) through to the transition to BSC, ALC became significantly lower, while the NLR and platelet-to-lymphocyte ratio (PLR) became significantly higher (p < 0.001 for all). This association was independent of hormone receptor status. Cox proportional hazard modeling found patients with hormone receptor-negative and a lower baseline ALC had a significantly shorter overall survival (p = 0.030 and p = 0.019, respectively). We observed that peripheral blood markers gradually changed with MBC disease progression. Our data suggest that baseline ALC may be a potential prognostic marker after recurrence.

Absolute Lymphocyte Count as an Independent Prognostic Factor in Metastatic Breast Cancer: A Retrospective Study

Introduction: Recently, absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) have been reported to be prognostic and/or predictive factors in breast cancer. However, most of the investigations on the relationship between systemic inflammatory markers and prognosis have been conducted perioperatively, with few studies reporting on patients with metastatic or recurrent breast cancer (MBC). Here, we investigated the role of ALC and NLR as prognostic factors of MBC. Methods: This was a retrospective observational study of patients with MBC treated at the University of Tsukuba Hospital between 2013 and 2020. ALC and NLR clinical data were obtained from the patients’ charts. Based on the previous reports, the cutoff value of ALC was set at 1,500/µL and that of NLR, at 3. We investigated the prognostic significance of ALC and NLR. Results: About 80% of the 243 included patients were hormone receptor-positive, 20% were HER2-positive, and 10% were triple negative. The patients were grouped as follows: 114 (46.9%) and 129 (53.1%) in the high and low ALC groups and 145 (59.7%) and 98 (40.3%) in the high and low NLR groups, respectively. The group with high ALC at diagnosis of MBC showed significantly better prognosis (p = 0.002), and the median overall survival (OS) was 70.9 months, as compared with 40.2 months for the low ALC group. On multivariate analysis, visceral metastasis, subtype, and ALC were independent variables for OS; the NLR status was not correlated with OS. Conclusions: Analysis of real-world data suggests that ALC at diagnosis of MBC is an independent prognostic factor.

Prognostic Significance of Initial Absolute Lymphocyte Count in Adjuvant Radiotherapy for Pancreatic Adenocarcinoma.

Background: This study aimed to investigate the impact of absolute lymphocyte count (ALC) on clinical outcomes in patients treated with adjuvant RT with or without chemotherapy for pancreatic adenocarcinoma. Methods: From 2001 to 2015, 68 patients underwent curative surgery followed by adjuvant RT. Chemotherapy was administered concurrently or sequentially with RT. We analyzed the clinical impact of the initial ALC level on locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS). Results: With a median follow-up of 13.7 months (range: 3.1–61.3), the 3 year OS, LRRFS, and DMFS are 25.4%, 40.0%, and 26.6%, respectively. The OS and LRRFS of the high initial ALC group (≥ 1540 × 106/L) are significantly higher than that of the group with lower initial ALC (3 year OS: 32.6% vs. 18.6%, p = 0.036; 3 year LRRFS: 53.5% vs. 27.0%, p = 0.031). In multivariable analyses, initial ALC level is the significant prognostic factor affecting LRRFS (HR = 0.457, p = 0.028) and OS (HR = 0.473, p = 0.026). Conclusions: Initial ALC could have potential prognostic significance in patients with pancreatic adenocarcinoma receiving adjuvant RT with or without chemotherapy. Further studies are warranted to investigate the role of adjuvant RT, considering the initial ALC.

Risk factors for development of lymphopenia in dimethyl fumarate-treated patients with multiple sclerosis

BackgroundDimethyl fumarate (DMF, Tecfidera®) is a first-line disease-modifying therapy for relapsing-remitting multiple sclerosis. Lymphopenia is a frequent reason for discontinuation in fumarate-treated patients. Management strategies to minimize risk of lymphopenia are warranted. ObjectiveThe aims of this study were to investigate the correlation of body mass index (BMI), baseline absolute lymphocyte count (ALC), age and sex with risk of DMF-induced lymphopenia in MS patients. MethodsThe study was a retrospective cohort study of 452 MS patients who had been prescribed DMF at six clinics in two Danish regions between May 2014 and September 2017. Data on lymphocyte counts, BMI, age, sex, and reason for discontinuation of DMF were collected through the Danish Multiple Sclerosis Registry, with follow- up to two years after treatment start. Results28.5% of patients had lymphopenia grade II or higher at some time in the first two years of DMF treatment. Increased risk of lymphopenia was observed in patients with baseline ALC of 1.00–1.49×109 cells/L (odds ratio, OR 5.48, p<0.0001) and 1.50–1.99×109 cells/L (OR 2.08, p = 0.0009). Reduced risk of lymphopenia was observed in patients with ALC of 2.00–2.49×109 cells/L (OR 0.51, p< 0.01) and ≥ 2.50×109 cells/L (0.12, p<0.0001). Patients aged ≥ 56 years had an increased risk of lymphopenia (OR 3.58, p<0.001), and patients with BMI ≥ 30 kg/m2 had a decreased risk of lymphopenia (OR 0.53, p value = 0.03). ConclusionLow baseline ALC and older age were risk factors for DMF-induced lymphopenia, while BMI ≥ 30 kg/m2 and high baseline ALC were protective factors for developing lymphopenia in MS patients treated with DMF.

COVID-19 Infection in Renal Transplant Recipients at Dubai Hospital: Incidence, Clinical Profile, and Outcome

Background: Renal transplant recipients are at risk to acquire COVID-19 infection quite frequently, owing to their immunocompromized state. Nevertheless, data on the effects of this infection on patients and graft function are sparse from the Arab world. Methods: This retrospective cohort study was conducted in Dubai Hospital from April 1, 2020, to August 1, 2021. We analyzed 42 COVID-19-positive renal transplant recipients’ data. Information concerning demographics, comorbidities, medications, clinical and laboratory data, and outcomes was collected from the electronic medical records. Univariate analyses were performed to determine the association of acute kidney injury (AKI) with in-hospital mortality. Results: Median age was 47.46 (17–66) years; about 59% of patients were male. Eleven (26.19%) patients developed AKI during hospitalization. On admission high ferritin, C-reactive protein, creatinine, and low absolute lymphocyte count are identified risk factors for in-hospital AKI. Seven (21.87%) patients had their calcineurin inhibitor levels touch a toxic peak possibly due to an interaction with antivirals. Mortality was 14.28%, and the same number of patients required mechanical ventilation during treatment. Conclusion: A significant number of renal transplant recipients suffered from AKI during COVID-19 infection, and the mortality rate in this study population was less than in studies from other countries in the region. More insights are required to manage this infection in renal transplant recipients.

Clinical Significance of Preoperative Hematological Parameters in Patients with D2-Resected, Node-Positive Stomach Cancer.

The purpose of the present study was to investigate the clinical significance of preoperative hematological parameters in patients with advanced stomach cancer, and to explore who might benefit from adjuvant concurrent chemoradiotherapy (CCRT) compared to chemotherapy alone. Among 1032 patients with node-positive stomach cancer who had a confirmed diagnosis after complete D2 resection, and who received adjuvant chemotherapy alone or CCRT, a total of 692 patients was selected using propensity score matching. Among absolute neutrophil count, absolute lymphocyte count (ALC), absolute monocyte count (AMC), platelet count, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, AMC was the most relevant prognostic factor for overall survival and recurrence-free survival (hazard ratio (HR) 1.674, 95% confidence interval (CI) 1.180–2.376; HR 1.908, 95% CI 1.650–2.695, respectively). In a subgroup with a high ALC, patients treated with adjuvant CCRT had a favorable recurrence-free survival (HR 0.620, 95% CI 0.393–0.980) compared to those treated with chemotherapy alone. Further study is needed to confirm our findings and to develop tailored adjuvant treatment.

P866: CORRELATIVE ANALYSIS TO DEFINE PATIENT PROFILES ASSOCIATED WITH MANUFACTURING AND CLINICAL ENDPOINTS IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS TREATED WITH IDECABTAGENE VICLEUCEL (BB2121)

Background: The anti-B-cell maturation antigen (BCMA) autologous chimeric antigen receptor (CAR) T cell therapy idecabtagene vicleucel (ide-cel; bb2121) has achieved deep and durable responses in relapsed/refractory multiple myeloma (RRMM) patients (Munshi, N Engl J Med 2021). Prior studies have described the correlation between patient characteristics and clinical outcomes from CD19 CAR T cell therapy (Finney, J Clin Invest 2019; Fraietta, Nat Med 2018). Aims: We sought to define patient profiles correlated with manufacturing and clinical endpoints in RRMM patients treated with ide-cel in clinical trials using unsupervised clustering and multivariate machine learning across multiple key variable domains. Methods: Clinical and manufacturing data were harmonized across 164 RRMM patients treated with ide-cel in KarMMa (NCT03361748) and KarMMa-2 cohort 1 (NCT03601078). Based on individual multivariate importance, 10 selected peripheral blood mononuclear cell (PBMC), drug product (DP), and in-process cell growth variables were used to define patient clusters. Random forest classifiers were generated to identify patient characteristics associated with manufacturing and clinical endpoints. Wilcoxon rank sum and Kruskal-Wallis tests were used to compare 2 and 3+ categorical groups; Cox proportional hazards were used to compare groups with time-to-event data. Results: Using an unsupervised method, 4 patient clusters were identified that represented 10%, 57%, 15%, and 18%, respectively, of the total 164 patients. Cluster 4 was the most favorable and was characterized by a higher frequency of T cells in PBMCs; increased T-cell size during manufacturing; higher DP T-cell transduction, potency, and vector copy number; and ultimately a > 3-fold higher CAR T cell yield compared with the least favorable cluster 1. Cluster 2 contained most patients and was associated with intermediate manufacturing endpoints. Patients in cluster 4 had a higher complete response rate, longer progression-free survival, and were defined by lower tumor burden, higher absolute lymphocyte count (ALC), and longer washout period after alkylator treatment, among others (Table). Image:Summary/Conclusion: The current study identified patient profiles in RRMM using accessible laboratory or medical history data that correlated with longitudinal outcomes. These findings may inform patients likely to achieve improved outcomes with CAR T cell therapy.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

Absolute lymphocyte count and C-reactive protein-albumin ratio can predict prognosis and adverse events in patients with recurrent esophageal cancer treated with nivolumab therapy.

Predicting the prognosis and adverse events (AEs) of nivolumab therapy for recurrent esophageal cancer is very important. The present study investigated whether a simple blood biochemical examination could be used to predict prognosis and AEs following nivolumab treatment for relapse of esophageal cancer. A total of 41 patients who received nivolumab treatment for recurrent esophageal cancer after esophagectomy were analyzed. The absolute lymphocyte count (ALC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and C-reactive protein-albumin ratio (CAR) were assessed at the time of nivolumab induction as indices that can be calculated by blood biochemical examinations alone. Median values were 1,015 for ALC, 3.401 for NLR, 242.6 for PLR, 0.458 for MLR and 0.119 for CAR, and patients were divided into two groups according to values. A high ALC, low NLR, low PLR, low MLR and low CAR were associated with a better response to nivolumab. In addition, patients with the aforementioned indices, with the exception of low PLR, or better response were more likely to develop AEs in univariate analysis. In multivariate analysis, a high ALC [odds ratio (OR): 4.857, P=0.043] and low CAR (OR: 9.099, P=0.004) were identified as independent risk factors for AEs. Survival analysis revealed that overall survival and progression-free survival (PFS) rates after nivolumab treatment differed significantly between the high and low groups of ALC, NLR, PLR, MLR and CAR. The multivariate analysis identified a low ALC [hazard ratio (HR): 3.710, P=0.003] and high CAR (HR: 2.953, P=0.007) as independent poor prognostic factors of PFS. In conclusion, ALC and CAR have potential as biomarkers for outcomes of recurrent esophageal cancer following nivolumab treatment.

Correlative analysis to define patient profiles associated with manufacturing and clinical endpoints in relapsed/refractory multiple myeloma (RRMM) patients treated with idecabtagene vicleucel (ide-cel; bb2121), an anti-BCMA CAR T cell therapy.

8021 Background: The anti-BCMA autologous CAR T cell therapy ide-cel has achieved deep and durable responses in RRMM patients (Munshi, N Engl J Med 2021). Prior studies have described the correlation between patient characteristics and clinical outcomes from CD19 CAR T cell therapy (Finney, J Clin Invest 2019; Fraietta, Nat Med 2018). We sought to define patient profiles correlated with manufacturing and clinical endpoints in RRMM patients treated with ide-cel in clinical trials using unsupervised clustering and multivariate machine learning across multiple key variable domains. Methods: Clinical and manufacturing data were harmonized across 164 RRMM patients treated with ide-cel in KarMMa (NCT03361748) and KarMMa-2 cohort 1 (NCT03601078). Based on individual multivariate importance, 10 selected peripheral blood mononuclear cell (PBMC), drug product (DP), and in-process cell growth variables were used to define patient clusters. Random forest classifiers were generated to identify patient characteristics associated with manufacturing and clinical endpoints. Wilcoxon rank sum and Kruskal-Wallis tests were used to compare 2 and 3+ categorical groups; Cox proportional hazards were used to compare groups with time-to-event data. Results: Using an unsupervised method, 4 patient clusters were identified that represented 10%, 57%, 15%, and 18%, respectively, of the total 164 patients. Cluster 4 was the most favorable and was characterized by a higher frequency of T cells in PBMCs; increased T-cell size during manufacturing; higher DP T-cell transduction, potency, and vector copy number; and ultimately a &gt; 3-fold higher CAR T cell yield compared with the least favorable cluster 1. Cluster 2 contained most patients and was associated with intermediate manufacturing endpoints. Patients in cluster 4 had a higher complete response rate, longer progression-free survival, and were defined by lower tumor burden, higher absolute lymphocyte count (ALC), and longer washout period after alkylator treatment, among others (Table). Conclusions: The current study identified patient profiles in RRMM using accessible laboratory or medical history data that correlated with longitudinal outcomes. These findings may inform patients likely to achieve improved outcomes with CAR T cell therapy. Clinical trial information: NCT03361748. [Table: see text]

Lymphopenia and outcomes of bendamustine-based therapy in follicular lymphoma.

e19540 Background: Bendamustine plus rituximab (BR) is the preferred first-line immunochemotherapy for follicular lymphoma (FL) due to its efficacy and generally favorable adverse effect profile. However, it often causes prolonged lymphopenia, and impaired lymphocyte recovery after BR therapy has been recognized as a risk factor for opportunistic infections. On the other hand, little is known about the impact of profound lymphopenia on the overall treatment outcomes of BR. We examined the relationship between lymphopenia and treatment response in patients with FL who received BR at our institution. Methods: We retrospectively identified patients who received BR as first-line therapy for FL at the Lifespan Cancer Institute between October 2008 and November 2020. We used log-transformed absolute lymphocyte count (ALC) as the potential prognostic variable, integrated as the area under curve based on all available laboratory tests over the typical duration of BR (6 months). Outcomes included complete response to BR determined by post-treatment positron emission tomography or computed tomography, survival, and occurrence of hospitalization or herpes zoster on therapy. The association between ALC and survival or binary endpoints was examined using Cox or logistic models, respectively, adjusting for age, sex, cumulative bendamustine dose, and baseline ECOG performance status (PS). Results: We included 53 patients followed for a median of 69 months from start of BR. At treatment initiation, most patients had a PS of 0-1, stage III or IV disease, and high-risk lymphoma as defined by the Follicular Lymphoma International Prognostic Index (FLIPI) (Table). We observed an association between higher ALC during treatment and increased rates of CR (adjusted odds ratio, 2.50, 95% CI 1.04 – 6.00; p = 0.040), longer progression free survival (PFS) (adjusted hazard ratio [HR], 0.53, 95% CI 0.31 – 0.92, p = 0.023), and overall survival (OS) (HR, 0.45, 95% CI 0.23 – 0.87, p = 0.018). Higher ALC values during treatment and 1 month after treatment initiation were also associated with lower probability of hospitalization (p = 0.048 and p = 0.028, respectively). We did not find a statistically significant association between ALC and rates of zoster infection, but the number of observed events was low (n = 6). Conclusions: Our results suggest an association between higher ALC values during bendamustine therapy and improved treatment outcomes. Improvement in PFS, OS, and hospitalization rates with higher ALC values may be due relative preservation of nutritional balance and immune reserve. The association with survival should be confirmed in larger datasets and its potential mechanism elucidated.[Table: see text]

Absolute Lymphocyte Count as a Prognostic Factor for Cytomegalovirus Infection After Heart Transplantation

<h3>Purpose</h3> Previous studies have suggested a correlation between reduced absolute lymphocyte count (ALC) & cytomegalovirus (CMV) infection and have therefore highlighted the potential of ALC as a simple tool to predict CMV infection in transplant patients. This study aims to examine the prognostic value of ALC on CMV infection in heart transplant patients. <h3>Methods</h3> Clinical information and ALC data of all adult patients who received orthotopic heart transplantation between January 2004 and May 2019 were collected. We performed a multivariable Cox regression model that incorporates repeated measurements of ALC as a time-varying continuous prognostic factor in two ways, first as binary variable with a threshold of 610 cells/μL and secondly as a continuous variable. Furthermore, landmark analyses to evaluate the mean ALC level of the preceding month, at 1, 3 & 6 months were performed. <h3>Results</h3> 549 patients received heart transplantation during this study period. 407 patients met the inclusion criteria for the primary endpoint investigation. An ALC ≥610 cells/μL was associated with a significantly lower risk of CMV infection (HR 0.57; CI 0.40-0.83; p=0.003). The continuous approach showed similar results with a significantly reduced risk of infection in patients with higher ALC (HR[2-fold increase] 0.78; CI 0.66-0.91; p=0.002). Landmark analyses of mean ALC levels at month 1 & 3, respectively, after transplantation showed a significantly decreased risk of infection in patients with a higher mean ALC (HR[2-fold increase] 0.81; CI 0.65-0.99; p=0.043 & HR 0.46; CI 0.29-0.74; p=0.001). <h3>Conclusion</h3> Absolute lymphocyte count is strongly associated with CMV infection after heart transplantation. ALC value monitoring could serve as an additional tool to predict and minimize the risk of CMV infection.