Mean Absolute Lymphocyte Count Research Articles

Lymphopenia is Not the Primary Therapeutic Mechanism of Diroximel Fumarate in Relapsing-Remitting Multiple Sclerosis: Subgroup Analyses of the EVOLVE-MS-1 Study.

In EVOLVE-MS-1 (NCT02634307), mean absolute lymphocyte count (ALC) on diroximel fumarate (DRF) declined from baseline by approximately 28% in year1, then stabilized, similar to ALC decline observed with dimethyl fumarate (DMF). Prior studies reported that clinical efficacy of DMF was not substantially different in patients with and without lymphopenia. EVOLVE-MS-1-an open-label, 96-week, phase3 study-assessed DRF safety and exploratory efficacy in patients with relapsing-remitting multiple sclerosis. This study analyzes efficacy-related outcomes comparing (1) patients with lymphopenia (≥ 1 ALC below lower limit of normal [LLN]) and without (all ALCs ≥ LLN); (2) across quartiles stratified by week96 ALC decline from baseline: Q1 (≥ 47% decline); Q2 (30% to < 47% decline); Q3 (12% to < 30% decline); Q4 (< 12% decline). Baseline characteristics were similar between patients without (n = 593) and with lymphopenia (n = 452). At week96, adjusted annualized relapse rate (ARR; 95% confidence interval) was 0.14 (0.11-0.17) without lymphopenia and 0.12 (0.09-0.15) with lymphopenia. Estimated proportions with 12-week confirmed disability progression (CDP12) at week96 were 10.2% without and 9.3% with lymphopenia. When stratified by quartiles (Q1-Q4), ARR at week96 was 0.11 (Q1), 0.09 (Q2), 0.13 (Q3), and 0.17 (Q4). Estimated proportions with CDP12 at week96 were 9.6% (Q1), 10.2% (Q2), 5.7% (Q3), and 10.9% (Q4). At week96, no evidence of disease activity was achieved by 47.2% (Q1), 47.8% (Q2), 45.4% (Q3), and 37.3% (Q4) of patients. In DRF-treated patients in EVOLVE-MS-1, clinical and radiological measurements indicated reduced disease activity regardless of lymphopenia or magnitude of ALC decline from baseline; however, patients who had greater ALC declines appeared to have numerically lower ARR and higher proportions free from relapses and gadolinium-enhancing lesions compared with those with smallest decline. This supports prior evidence that, while lymphopenia may contribute to fumarate efficacy outcomes, it is not the primary mechanism of action. ClinicalTrials.gov identifier NCT02634307.

Assessment of the differences of hematological variables and their correlation with glycemic control among type 2 diabetes mellitus patients in Iraq: Comparative cross-sectional study

This research aimed to assess the hematological traits of male adults diagnosed with diabetes and investigate the relationship between blood sugar levels with hematological factors among patients. A cross-sectional comparison study was conducted at Fallujah Teaching Hospital from April 1 to July 30, 2023. The research comprised 185 volunteers, including 125 individuals with type 2 diabetes mellitus (65 with well blood sugar levels and 60 with poorly-regulated blood sugar levels) and 60 healthy individuals serving as controls. The evaluation of hematological parameters was conducted using Swelab-Alfa. An independent T-test was used for assessment. The patients exhibited substantially decreased mean absolute lymphocyte count, Hct, MCHC, and PLT values compared to the control group. The diabetic group had significantly higher mean values for total neutrophil count, absolute basophil counts, RDWSD, RDWCV, PDW, PLCR, and MPV than the control group. Patients with poor glycemic control had substantially elevated levels of Mon, Eos, Bas, MCHC, PLT, MPV, PLCR, and PCT. In contrast, individuals with poor glycemic control had substantially lower levels of Neu, RBC count, and PDW. The findings demonstrated a statistically significant positive connection between neutrophil count, MCV, MCH, MCHC, PDW, MPV, PLCR, and PCT with FBG. Lym, RBC count, and Hct exhibited a statistically significant inverse connection with FBG in individuals with type 2 diabetes mellitus (T2DM). This research demonstrated a notable impact of diabetes mellitus, poor glycemic control, and fasting blood glucose levels on some hematological markers.

OP03 Efficacy and safety of the oral selective sphingosine-1-phosphate-1 receptor modulator VTX002 in moderately to severely active Ulcerative Colitis: results from a randomised, double-blind, placebo-controlled, phase 2 trial

Abstract Background VTX002 is a novel oral selective sphingosine-1-phosphate-1 (S1P1) receptor modulator in development for the treatment of ulcerative colitis (UC). The efficacy and safety of VTX002 in patients with ulcerative colitis (UC) was assessed in a phase 2, multicentre, randomised, double-blind, placebo-controlled study (NCT05156125). Methods Adults (N=213) with moderately to severely active UC (modified Mayo score [MMS] 4-9) and inadequate response/intolerance to conventional and/or advanced (approved biologics or Janus kinase inhibitor) therapies were randomised 1:1:1 to once daily treatment with placebo (n=70), 30 mg (n=73) or 60 mg (n=70) VTX002 tablets for 13 weeks. Patients underwent a 6–8-day dose titration up to the assigned treatment dose. The primary endpoint was clinical remission (MMS stool frequency subscore ≤ 1, rectal bleeding subscore=0, and endoscopic subscore [ES] ≤ 1) at week 13. A protocol amendment limiting eligibility to patients with baseline MMS 5-9 resulted in 213 and 209 patients in the safety and efficacy populations, respectively. Key secondary endpoints were endoscopic improvement, symptomatic remission, histologic remission, and endoscopic improvement-histologic remission. Endoscopic remission and histologic-endoscopic mucosal improvement (HEMI) were also assessed (see Table 1 for outcome definitions). Adverse events (AEs) and laboratory abnormalities were assessed for safety. Results The primary endpoint of clinical remission at week 13 was achieved (27.9% of patients who received VTX002 60 mg vs 11.4% of patients who received placebo, ∆=16.5%, p=0.0184). Both doses of VTX002 achieved nominal statistical significance for all key secondary endpoints (Table 1). Significantly greater proportions of patients who received VTX002 60 mg achieved endoscopic remission and HEMI compared to patients who received placebo (29.4% VTX002 60 mg vs 7.1% placebo, ∆=22.3%, p=0.0012, and 32.4% VTX002 60 mg vs 10.0% placebo, ∆=22.4%, p=0.0026, respectively). A dose-dependent decrease of 67.7% and 53.9% in mean absolute lymphocyte count (ALC) from baseline was observed at week 8 for patients who received VTX002 60 mg and 30 mg, respectively. Most AEs were mild to moderate (Table 2). No AEs of bradycardia, atrioventricular block, serious infections, macular oedema, or deaths were reported. Conclusion The S1P1 receptor modulator VTX002 was well-tolerated and statistically superior to placebo for induction of clinical, endoscopic, histologic, HEMI, and symptomatic remission/response at week 13. These positive findings, including a dose-dependent pharmacodynamic reduction in ALC, support phase 3 development of VTX002 for treatment of UC.

P567 Impact of recent thiopurine use on ozanimod safety in patients with ulcerative colitis: a post hoc analysis of the phase 3 True North study

Abstract Background Ozanimod, a sphingosine 1-phosphate (S1P) receptor modulator that selectively targets S1P1 and S1P5, is approved for the treatment of moderately to severely active ulcerative colitis (UC) in adults based on results from the phase 3 True North study (NCT02435992). Reductions in absolute lymphocyte count (ALC) are expected with ozanimod but not associated with treatment-emergent adverse events (TEAEs). This post hoc analysis explored the effect of recent use of thiopurines on ALC and safety outcomes in patients treated with ozanimod. Methods True North was a phase 3 trial of ozanimod induction and maintenance therapy in moderately to severely active UC. Patients in Cohort 1 were randomised to once-daily double-blind treatment with ozanimod 0.92 mg or placebo; patients in Cohort 2 received open-label ozanimod for a 10-week induction period. Patients on concomitant thiopurines were required to stop therapy at study start without a washout period. In this post hoc analysis, patients were stratified by recent prior thiopurine use (within 90 days of ozanimod initiation). ALC was assessed at baseline; ALC, TEAEs, and infectious outcomes were assessed during the induction period at Weeks 5 and 10. Results Of the 1012 patients in True North, 796 were treated with ozanimod and analysed (n=57 with recent thiopurine exposure; n=739 without recent thiopurine exposure). At baseline, mean ALC (×109/L [SD]) was slightly lower in patients with than without recent thiopurine use (Table). Both groups had similar baseline incidence of ALC &amp;lt;200 cells/µL (0%) and &amp;lt;500 cells/µL (range 0.0–0.3%). While ALC &amp;lt;200 cells/µL and &amp;lt;500 cells/µL were more prevalent among patients with than without recent thiopurine use (Figure), the reductions from baseline to Week 10 in ALC were similar in both groups (Table). Rates of infection were also similar in patients with recent thiopurine use (14.7% in Cohort 1 and 13.0% in Cohort 2) and without recent thiopurine use (10.4% and 12.5%, respectively). The most frequent infection was nasopharyngitis in both groups: 8.8% in Cohort 1 and 0% in Cohort 2 in patients with recent thiopurine use; 3.0% and 2.9%, respectively, in patients without recent thiopurine use. There were no serious adverse events (AEs) related to ozanimod treatment, and treatment discontinuations were similar in patients with and without recent thiopurine exposure. Conclusion Lower ALC was observed in patients starting ozanimod within 90 days of thiopurine use but was not associated with an increased incidence of infection or serious AEs. The findings suggest switching from thiopurines to ozanimod without a washout period may be safe and tolerable.

Normal Tissue Complication Probability Modeling of Severe Radiation-Induced Lymphopenia Using Blood Dose for Patients With Hepatocellular Carcinoma

PurposeThis study aims to develop a normal tissue complication probability (NTCP) model to estimate the risk of severe radiation-induced lymphopenia (SRIL, absolute lymphocyte count (ALC) < 500/μL) by using the blood dose of hepatocellular carcinoma (HCC) patients. Methods and MaterialsWe retrospectively collected data from 75 HCC patients who received radiotherapy (RT) between 2015 and 2018. The hematological dose framework calculated blood dose-volume histograms (DVHs) using a predefined blood flow model, organ DVHs, the number of treatment fractions, and beam delivery time. A Lyman-Kutcher-Burman (LKB) model with a generalized equivalent dose was used to establish the NTCP model, reflecting the whole blood DVHs. The optimization of the LKB parameters was conducted by minimizing a negative log-likelihood function. ResultsThere were 6, 4, 18, 33, and 14 patients in the groups with radiation-induced lymphopenia grades 0, 1, 2, 3, and 4, respectively. The median pre/post-RT ALC were 1410/μL (range, 520–3710/μL) and 470/μL (range, 60–1760/μL), respectively. There was a correlation between blood mean dose and ALC depletion (Pearson r = -0.664; p < 0.001). The average blood mean doses in each radiation-induced lymphopenia group were 2.90 Gy (95% CI, 1.96–3.85 Gy) for grade 0–1, 5.29 Gy (95% CI, 4.12–6.45 Gy) for grade 2, 8.81 Gy (95% CI, 7.55–10.07 Gy) for grade 3, and 11.69 Gy (95% CI, 9.82–17.57 Gy) for grade 4. When applying developed an NTCP model to predict SRIL, the area under the receiver operating characteristic curve and Brier score were 0.89 and 0.12, respectively. ConclusionWe developed the first NTCP model based on whole blood DVHs for estimating SRIL after abdominal RT in HCC patients. Our results showed a strong correlation between blood dose and ALC depletion, suggesting the potential to predict the risk of SRIL occurrence for using blood dose.

Attrition after Referral for Chimeric Antigen Receptor T-Cell (CAR-T) Products in Multiple Myeloma (MM)

Introduction: Chimeric antigen receptor T-cell (CAR-T) products have shown an impressive response in relapsed/refractory MM patients (pts). The pivotal KarMMa-3 (Otero-Rodriguez P et al, NEJM, 2023) and CARTITUDE-4 (San Miguel J, et al, NEJM, 2023) studies showed that infusion of idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) was superior to other standard of care therapies. However, some pts in these studies were unable to receive CAR-T even after being deemed eligible for apheresis. In KarMMa-3, 12/140 pts who completed apheresis did not receive their cells, 3 due to disease progression/death and 1 due to a true manufacturing failure. In CARTITUDE-4, 16/113 pts who completed apheresis did not receive their cells, with 9 dying prior to infusion and 0 having true manufacturing failures. Other studies have shown that factors like peripheral CD3 count (PCD3) affected the probability of a successful apheresis (Rytlewski et al, ASCO 2022). Known reasons for CAR-T attrition include lack of available spots, true manufacturing failures, death post-apheresis but prior to infusion (PAD; due to infection and/or disease progression), and cell product issues necessitating an expanded access program (EAP). This study aimed to find patient- and disease-specific variables associated with increased rates of CAR-T attrition. Methods: We retrospectively reviewed the medical records of all pts who were approved for either ide-cel or cilta-cel as standard of care (SOC) treatment for MM at MD Anderson between August 2021 and June 2023. The study was approved by the Institutional Review Board at MD Anderson. Pts were classified by CAR-T product received, and the number of apheresis procedures required to produce viable product. They were then classified based on need for EAP. Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age and lab measurements, and frequency counts and percentages for categorical variables such as stage, gender, comorbidity, treatment, and response were obtained. Fisher's exact test or Chi-square test was used to evaluate the association between two categorical variables. Wilcoxon rank sum test or Kruskal-Wallis test was used to evaluate the difference in a continuous variable between or among patient groups. Kaplan-Meier method was used to estimate overall survival and progression free survival for the pts who received CAR-T infusion. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for all the analyses. Results: Data from 153 pts were included. High-risk features, defined as the presence of high-risk cytogenetics, extramedullary disease, or R-ISS stage III, were present in 125 (81.7%), and 84 (54.9%) were penta-refractory. CAR-T cells were infused successfully in 86 (56.2%) pts, including 5 who were infused via EAP. Of the 67 pts who did not get infused, 26 (38.2%) died prior to apheresis, 8 (11.9%) were PAD, 10 (14.9%) were treated with a bispecific agent due to lack of available manufacturing slots, and 3 (4.5%) had true manufacturing failures. Of the 8 patients that were PAD, 2 died due to progression of disease, 4 died from complications of inpatient bridging chemo, and 2 died from complications from lymphodepleting chemo. For all pts with manufacturing failures, their apheresis had a low dose, with 2 out of 3 having PCD3 &amp;lt; 5%. The mean absolute lymphocyte count (ALC) at apheresis was significantly higher in the EAP group (n=5) compared with the non-EAP group, but significantly lower in the manufacturing failures group (n=3) compared with the successful CAR-T manufacturing (n=86) group (Table 1). For the overall cohort of pts receiving CAR-T (n=86), the median progression-free (PFS) and overall survival (OS) rates were 11.7 and 18.8 months, respectively (Figure 1). Conclusion: The PFS and OS for all pts, including those who received their CAR-T through EAP, were excellent. ALC at the time of apheresis was a predictor of true manufacturing failure. Surprisingly, pts successfully treated on EAP had an increased ALC compared with those receiving SOC. Further comparative studies of pts with barriers to CAR-T are needed to identify other variables that increase adverse outcomes so that these can be addressed. Hopefully, with a better understanding of the barriers patients have, we can ensure that more pts get access to this efficacious treatment.

COVID-19 infection in Libyan chronic hemodialysis patients: Prevalence, risk factors, severity and predictors of mortality

Background: Chronic kidney disease (CKD) is associated with the increased risk of both outpatient and inpatient pneumonia. This association is independent of comorbid diabetes, cardio-vascular disease (CVD), asthma, and chronic obstructive airway disease. Dialysis patients are considered at risk groups for SARS-CoV-2 infection; Short-term mortality in patients on chronic hemodialysis who were hospitalized with COVID-19 was high. Outcomes in those requiring intensive care unit (ICU) and mechanical ventilation management were poor. Aim: This study mainly aimed to identify the prevalence, risk factors, severity and predictors of mortality in Libyan hemodialysis patients infected with COVID- 19. Methods: In this retrospective cohort study, data of CKD patients on maintenance hemodialysis diagnosed with COVID-19 infection from two large dialysis centers in Libya were collected and analyzed using SPSS version 22 for .demographic, clinical and laboratory profiles. Results: The data of 810 patients from two hemodialysis centers in Libya showed infection rate was 10.2 %, and the overall mortality was 26.5% (39/83) 47% of patients needed admission to ICU for supportive mechanical ventilation (SPO2 ranged from 76-92%). The biochemical and laboratory data showed a decreased mean absolute lymphocyte counts. A high neutrophil-lymphocyte ratio (NLR), and a mild decrease in platelet counts. C-reactive protein (CRP), fibrinogen, ferritin, and D-dimer were also high at admission. (22/83, 26.5%) of total patients, and (17/39) 43.6% of ICU patients died in less than 28 days after COVID-19 diagnosis. Conclusions: In CKD patients on maintenance hemodialysis diagnosed with COVID-19 infection; severity of disease at presentation, need for invasive supportive mechanical ventilation, older age, raised serum glutamic oxaloacetic transaminase, and lower level of albumin may have been valuable predictors of mortality and poor outcomes.

Early mean absolute lymphocyte count in acute necrotizing pancreatitis is associated with infected pancreatic necrosis.

Peripheral absolute lymphocyte count (ALC) has the potential to predict infected pancreatic necrosis (IPN), but requires verification. This study aimed to assess whether early mean absolute lymphocyte count is associated with the development of IPN in ANP patients using pooled data from a multicenter, randomized controlled trial and a retrospective study. The study subjects are from the TRACE trial and a single-center cohort study. ALC during the first seven days was used to define early mean ALC. The entire cohort was then divided into quartiles of early mean ALC. Multivariable Cox proportional hazards regression (MCPHR) model was used to assess the association between early mean ALC and 90-day IPN. A total of 660 patients (median age, 44years; 63.8% males) were included and 157 (23.8%) developed IPN within a 90-day period. The median (interquartile range, IQR) of the early mean ALC is 1.07 (0.80-1.36). All the study subjects were evenly divided into 4 groups: quartile-1 (0.33-0.79*10^9/L), quartile-2 (0.80-1.06*10^9/L), quartile-3 (1.07-1.36*10^9/L) and quartile-4 (1.37-4.01*10^9/L). The incidence of 90-day IPN was 38.3%, 25.7%, 19.2% and 12.2% for each group, respectively. In the MCPHR model, the lowest early mean ALC (quartile-1) was found to be an independent risk factor of 90-day IPN with a hazard ratio (95%CI) of 2.21 (1.28-3.81) compared to the highest mean ALC(quartile-4) group. Among patients with ANP, early mean ALC was significantly associated with the development of IPN. Preventive strategies should be considered in patients with reduced ALC.

Changes in White Blood Cells in Solid Cancers Before First Cycle and After the Third Cycle of Chemotherapy

Introduction: Chemotherapy is a nonspecific drug that kills or damages fast growing cells; cancer cells and noncancerous body cells including white blood cells (WBCs). Changes to the WBCs can begin as early as few days to a week after starting chemotherapy treatment. This study was conducted to assess the effect of three cycles of chemotherapy on white blood cells compared to that at diagnosis of solid cancers. Methods: This is a prospective study included 100 patients diagnosed with solid cancers and subjected to chemotherapy in the National Cancer Centers in Aden and Taiz governorates, during 2020. Complete blood count was done for all patients prior to the first cycle and after the third cycle of chemotherapy. Results: The mean total WBCs count, absolute neutrophil count (ANC), absolute eosinophile count (AEC) and absolute monocyte count (AMC) were statistically significantly lower after third cycle when compared to that before first cycle. Meanwhile, the mean Absolute Lymphocyte count (ALC) and absolute basophile count (ABC) did not show any significant difference. Only 9.0% of solid cancer patients had leucocytosis at diagnosis. The percentage of patients with low WBCs count significantly increased after the third cycle, while the percentage of patients with normal WBCs count significantly decreased after the third cycle. The ANC showed a significant statistical difference between the counts prior to the first cycle of chemotherapy and after the third cycle of chemotherapy. Normal ANC was observed among 74.0% of patients before the first cycle of chemotherapy and it decreased to 53.0% after the third cycle. Neutropenia with all grades of severity was statistically significantly higher after the third cycle. The mean total WBCs count decreased after the third cycle in all types of cancers, and this decrease was statistically significant in patients with breast cancers and lymphomas, while other cancers did not show such significance Conclusion: This study concluded that in patients with solid cancer, WBCs and mainly the ANC significantly decreased after the third cycle of chemotherapy to a level that may be severe to affect patients’ overall health.

PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSIS OF AMISELIMOD, A SELECTIVE SPHINGOSINE 1-PHOSPHATE RECEPTOR MODULATOR, IN HEALTHY SUBJECTS: RESULTS FROM A PHASE 1 STUDY

Abstract BACKGROUND Amiselimod is a selective sphingosine 1-phosphate receptor modulator in development for inflammatory bowel disease. It is converted to its active metabolite, amiselimod phosphate (amiselimod-P), and has a long half-life and slow accumulation to steady state. We evaluated a multiple-dose titration regimen to determine the plasma pharmacokinetic (PK) profile of amiselimod and amiselimod-P at steady state for the 0.4 mg QD therapeutic dose on day 13 and for the 0.8 mg QD supratherapeutic dose on day 26. We also investigated the pharmacodynamic (PD) effect of amiselimod on absolute lymphocyte counts (ALCs). METHODS A randomized, double-blind, multiple-dose, placebo-controlled, parallel study with a nested crossover design assessed amiselimod and amiselimod-P. Healthy adults received a single dose of placebo followed by oral amiselimod, which was upwardly titrated in doses ranging from 0.4 to 1.6 mg QD to rapidly achieve steady-state concentrations for the 0.4 mg QD and 0.8 mg QD doses within a 28-day treatment period. The PK parameters of amiselimod and amiselimod-P (on days 1, 13 and 26) included the geometric mean (geometric coefficient of variation percentage [CV%]) maximum plasma concentration (Cmax), median (minimum, maximum) time to Cmax (Tmax), geometric mean (geometric CV%) area under the concentration-time curve (AUC) from time 0 to the last measurable concentration, and geometric mean (geometric CV%) AUC from time 0 to 23.5 hours postdose (AUC0-23.5). Multidose PD were evaluated by changes in ALCs. RESULTS The PK population included 95 amiselimod-treated participants and the PD population included 190 participants who received amiselimod or placebo. On day 13, the steady-state AUC and Cmax for amiselimod 0.4 mg QD increased by 10-fold for amiselimod and by 4-fold for amiselimod-P compared with day 1. On day 26, the steady-state AUC0-23.5 and Cmax for amiselimod 0.8 mg QD increased by 1.9-fold for amiselimod and by 1.8-fold for amiselimod-P compared with day 13. The median Tmax of plasma amiselimod and amiselimod-P were similar on all 3 days and were reached at 11 to 12 hours postdose for amiselimod and at 10 hours postdose for amiselimod-P. The mean ALCs for amiselimod exhibited a gradual decrease from predose (1.681 × 103/uL) to a nadir of 0.424 × 103/uL on day 27. CONCLUSIONS The abbreviated amiselimod dosing titration regimen reached steady state within 14 days for the therapeutic 0.4 mg QD regimen and within 26 days for the supratherapeutic 0.8 mg QD regimen; expected decreases in ALCs were observed following amiselimod.

The Role of Hematological Parameters in Predicting the Death of Hospitalized Patients with COVID-19.

The role of the hematologic indicators in the identification of severe or critical patients requires further investigation. In this study, we focused on predicting Covid-19 patients at risk of progression using blood parameters. We performed a retrospective study including 444 patients with confirmed Covid-19. Hematological parameters were evaluated. The logistic regression analysis was performed with step-wise method with dependent variables such as intensive care units admission, partial pressure of oxygen saturation, and mortality. Also, independent variables such as hematological parameters, age and sex to assess variables that are likely to predict patients at risk of progression. Patients in intensive care units had significantly higher mean absolute neutrophil count than outpatients (P < 0.001). There was a statistically significant difference in the mean absolute lymphocyte count between dead and survived patients (P = 0.015). Multivariate analysis confirmed the positive association of the white blood cells (P < 0.001), absolute neutrophil count (P < 0.004), red cell distribution width (P < 0.001), and lactate dehydrogenase (P = 0.007) to be positively associated with the admission of Covid-19 patients in the intensive care units and the absolute monocyte count (P = 0.012, Odds ratios = 0.100, CI95% = 0.066-0.605) to be negatively associated with mortality. Based on the results of our study, it is recommended to use hematological data to make clinical decisions and evaluate the patient's prognosis.

Once Monthly Elotuzumab and Lenalidomide Plus Dexamethasone for Multiple Myeloma: A Multicenter Observation Study

Introduction: Elotuzumab and lenalidomide plus dexamethasone (ERd) is a standard salvage chemotherapy for multiple myeloma, and elotuzumab is commonly administered every 2 weeks after cycle 3 (conventional ERd). Alternatively, elotuzumab may often be used every 4 weeks (monthly ERd) in real-world practice. The purpose of this multicenter observational study was to investigate the efficacy and tolerability of monthly ERd. Methods: We investigated the efficacy and tolerability between conventional and monthly ERd regimens for the myeloma patients in six institutes retrospectively. Results: Seventy-five patients were included in this study. The median patient age was 68 years. The median number of prior chemotherapies was two (1–5). The number of patients with prior lenalidomide exposure was 57 (76.0%). The numbers of progressive disease (PD) and non-PD before ERd were 23 (30.7%) and 52 (69.3%), respectively. The frequency of PD before ERd was significantly lower in the monthly ERd group than in the conventional ERd group. In 26.9 months of median follow-up period, the 2-year progression-free survival (PFS) rate in the monthly ERd group was significantly longer than that in the conventional ERd group (95.0% and 62.0%, hazard ratio 0.082, p = 0.002). However, no significant difference in PFS between these two ERd groups was found using multivariate analysis. The complete response rates were similar between the monthly and conventional ERd groups (55.0% and 32.7%, p = 0.109). There was no significant difference in the incidence of adverse events between the monthly and conventional ERd groups (35.0% and 54.5%, p = 0.192). There was no significant difference in the kinetics of the mean absolute lymphocyte count, CD4, CD8, CD16, CD56, and CD57 positive lymphocyte counts, and CD4 to CD8 ratio between the monthly and conventional ERd groups. Discussion: The efficacy and tolerability of monthly ERd were similar to those of conventional ERd. Thus, monthly ERd might be a reasonable option, considering the quality of life of patients and convenience.

S761 Association Between Absolute Lymphocyte Count and Ozanimod Efficacy/Safety in Patients With Moderate/Severe Ulcerative Colitis: Results From the Phase 3 True North Study

Introduction: Ozanimod (OZA) is approved in the USA and EU for treatment (tx) of moderate/severe UC. OZA binding internalizes S1P1 receptors, reducing egress of lymphocyte subsets into circulation. OZA was approved in this patient (pt) population based on results of the phase 3 True North (TN) study (NCT02435992). Methods: We evaluated association between absolute lymphocyte count (ALC) and OZA efficacy/safety during TN’s induction period (IP) and maintenance period (MP). Pts were randomized to double-blind (DB) OZA 0.92 mg or placebo (PBO) or open-label (OL) OZA during 10-week (W) IP. Pts with clinical response to OZA at W10 were rerandomized to DB OZA or PBO for MP through W52. Rectal bleeding (RB), stool frequency (SF), composite Mayo, Physician’s Global Assessment (PGA), and endoscopy scores were assessed at baseline and as clinical outcomes at W10 and W52. Efficacy endpoints (EPs; clinical remission, clinical response, endoscopic improvement, mucosal healing, and histologic remission) were assessed at W10 and W52. Tx-emergent adverse events (TEAEs) and ALC were evaluated at baseline and W5, W10, W18, W28, W40, and W52. Results: During IP, 645 pts received DB OZA (n=429) or PBO (n=216) and 367 received OL OZA; for MP, 230 and 227 OZA-treated pts were rerandomized to OZA and PBO, respectively. Baseline ALC was not significantly correlated with clinical outcome at W10 or W52 as measured by changes from baseline RB, SF, Mayo, PGA, and endoscopy scores in pts on OZA or PBO. Baseline ALC was not predictive or prognostic for W10 and W52 responses based on the efficacy EPs. Reductions from baseline in mean ALC occurred by W5 with OZA and were significantly greater with OZA (53-54%) vs PBO (2.3%; P< .001). ALC plateaued by W10 and was maintained through W52 in pts on continuous OZA. ALC returned to PBO levels by W52 in pts who switched to PBO during MP. Change in ALC at W10 was generally not significantly correlated with changes in clinical outcomes at W10 or W52. Change in ALC at W5 was not predictive of W10 response; change in ALC at W10 was not predictive of W52 response. Reductions from baseline in ALC at all weeks were similar in OZA-treated pts with/without ≥1 TEAE and with/without infection TEAEs. Conclusion: ALC reductions occurring with OZA were reversed upon tx discontinuation and were not associated with TEAEs. Baseline ALC and ALC reductions were not predictive or prognostic for response. These findings support ALC as a pharmacodynamic biomarker but not as a prognostic or predictive biomarker.

Blood counts in children with Down syndrome

Children with Down syndrome (DS) are more likely to have hematologic and immunologic abnormalities compared to their typically developing peers, but normal ranges have not been defined. The goal of this study was to create references for complete blood counts (CBCs) in patients with DS. A retrospective investigation of 355 (male=196, 55.2%; mean age=6.49years, SD=5.07) healthy pediatric patients with DS who received a CBC between 2011 and 2017 as part of their medical care at a single, large, pediatric teaching hospital. Control data on 770 healthy patients without DS were included. Descriptive statistics were performed on demographic and clinical characteristics. Kruskal-Wallis H tests, nested analysis-of-variance tests, and t-tests were run to determine the significant associations. Age-related normative curves for healthy children with DS outlining 2.5th, 25th, 50th, 75th, and 97.5th percentiles are provided for total white blood count, hemoglobin concentration, hematocrit, mean corpuscular volume, and platelet, absolute neutrophil, absolute lymphocyte, eosinophil, monocyte, and basophil counts. Statistical differences were found between children with and without DS receiving care at the same hospital based on matched age/sex groups. This study demonstrates that patients with DS have different reference ranges for multiple blood counts compared to those without DS, creating a new resource for pediatricians to refer to when evaluating CBCs in this population.

Low postoperative lymphocyte count increases risk of progression in human papillomavirus associated oropharyngeal cancer.

We aim to explore the prognostic role of absolute lymphocyte count (ALC) before, during, and after treatment on oncologic outcomes in human papillomavirus associated oropharyngeal cancer (HPV(+)OPSCC). Retrospective cohort at a tertiary center, 2006-2018. Multivariable Cox regressions were used to determine the effect of ALC on risk of progression. Univariate linear regression was performed to determine clinical factors associated with lower ALC. All 197 patients underwent primary surgery. Mean (SD) ALC nadirs (×109 cells/L) were: baseline (N= 149): 1.69 (0.56); postoperative (N= 126): 1.58 (0.59); post-RT (N= 141): 0.68 (0.35) and long-term (N= 105): 0.88 (0.37). Lower baseline ALC nadir was associated with worse overall survival (HR 3.85, 95%CI: 1.03-14.29, p= 0.04). Lower postoperative ALC nadir was associated with higher risk of progression (HR 2.63, 95%CI: 1.04-6.67, p= 0.04). Lower baseline ALC is associated with worse survival, whereas lower postoperative ALC is associated with increased risk of progression in surgically treated HPV(+)OPSCC.

Prevalence of lymphopenia in patients with Fontan circulation without protein losing enteropathy

BackgroundLymphopenia without protein losing enteropathy (PLE) is found in patients with Fontan circulation on long term follow up. Fontan associated liver disease (FALD) is a serious complication in these patients. ObjectiveThe objective of this study is to assess the prevalence of asymptomatic lymphopenia in patients with Fontan circulation and its associations with other hematological and liver function parameters. MethodsRetrospective cohort study involving 48 patients with Fontan circulation. All patients had yearly complete blood count and liver function tests performed during their routine follow up. Patients with PLE were excluded. Lymphopenia defined as absolute lymphocyte count (ALC) < 1000 cells/μL and its correlation with other hematological and liver enzymes were studied. ResultsLymphopenia was present in 9 (18.75 %) patients and was found after 10 years of post Fontan duration in 7 patients, at 5.5 years in 1 patient, and at 6.7 years in 1 patient. The mean ALC of patients with and without lymphopenia was 748 ± 190.8 versus 2053 ± 844.9 cells/μL (P = 0.002). Patients with lymphopenia had lower total white blood cell count (3.9 ± 1.9 versus 6.02 ± 2.1 × 109/L, P = 0.006) and platelet counts (180.7 ± 94.6 versus 253.6 ± 80.3 × 109/L, P = 0.02). Lymphopenia correlated with elevated aspartate transaminase (AST) (43.2 ± 9 versus 29.8 ± 6.98 IU/L, P = 0.006), Gamma glutamyl transpeptidase (GGTP) (69.5 ± 61 versus 29.8 ± 6.98 IU/L, P = 0.04) and AST – platelet ratio index (APRI) (0.7 ± 0.5 versus 0.3 ± 0.1, P = 0.001). ConclusionAsymptomatic lymphopenia is common in patients with Fontan circulation. Identification of lymphopenia with associated thrombocytopenia, elevated AST, GGTP, and APRI are necessary as these are the markers of hepatic fibrosis. Further investigations, such as MRI and liver biopsy, can be considered in these patients.

P-060: A HIGHER GRANULOCYTE-LYMPHOCYTE RATIO IS ASSOCIATED WITH IMPROVED RED BLOOD CELL INDICES AND AGE IN DUFFY ANTIGEN-NEGATIVE SICKLE CELL DISEASE PATIENTS.

Purpose: A higher Neutrophil-Lymphocyte ratio (NLR) has been associated with poor prognosis in many diseases. Most Africans are neutropenic due to the duffy antigen null status. The duffy antigen null status however, has been associated with a higher risk of organ damage in people living with sickle cell disease (SCD). We therefore sought to determine the effect of the proportion of these blood cells to one another on SCD prognosis in Nigeria. Materials and methods: One hundred and thirty (130) sickle cell disease patients in steady state and 117 healthy age- and sex-matched controls were recruited from a tertiary institution in Nigeria. All the participants gave informed consents and blood samples were taken for Full Blood Count and phenotyping by High Performance Liquid Chromatography. Demographic and clinical details were obtained by questionnaire administration. Neutrophils make up over 90% of granulocytes, hence the granulocyte-lymphocyte ratio was determined from the available absolute counts of granulocytes and lymphocytes. A subset of 110 patients who were not on hydroxyurea was used for the analysis. The patients were divided into 3 age groups (< 7years, 8 – 17years and >17years). Data analysis was done using IBM SPSS version 23. Results: The mean absolute lymphocyte counts (ALC) and absolute granulocyte counts (AGC) in SCD patients (5.142 and 5.295 x103/µL respectively) were higher than in controls (2.952 and 2.171 x 103/µL respectively) (p<0.001). ALC and AGC decreased with age (p<0.001, p=0.02 respectively) in the SCD patients. A similar trend in ALC was observed in the control group while there was no significant difference in the AGC of children <7years and adults (>17years) (Fig 1). The mean granulocyte-lymphocyte ratio (GLR) in SCD patients increased from 1.01 in children <8years to 1.40 in adults. For the control group, the GLR decreased from 0.75 in children <8years to 0.66 in children 8–17years old and an increase to 0.95 in adults (Fig 2). In the SCD patients, GLR was positively correlated with RBC (rs=0.351, p<0.001), HGB (rs=0.256, p=0.004), HCT (rs=0.295, p<0.001) and HbA2 (rs=0.293, p<0.001). HbA2 was positively correlated with RBC (rs=0.201, p=0.028) while HbF was negatively correlated with RBC (rs=-0.257, p=0.006) and showed no correlation with the GLR (rs=-0.008, p=0.930). ALC however had a negative correlation with RBC (rs=-0.395, p<0.001), HGB (rs=-0.452, p<0.001) and HCT (rs=-0.395, p<0.001). AGC also had a negative correlation with HGB (rs=-0.245, p=0.006) and HCT (rs=-0.179, p=0.047). These relationships were not observed in the control group except for a positive correlation between HGB and GLR (rs=0.273, p=0.003) and a negative correlation between HGB and ALC (rs=-0.295, p=0.001). GLR was negatively associated with the frequency of painful crisis in the last one year (p<0.001). Conclusion: AGC and ALC decreased with age in our patients with an increase in the GLR. A positive correlation of GLR with RBC, HGB, HCT and HbA2 infers a protective role of a higher GLR/NLR to RBC survival in our patients. A higher GLR may be associated with better clinical outcomes, and neutropenia due to the duffy antigen null status may exacerbate the course of SCD in blacks.Fig 1. The mean absolute counts of granulocyte and lymphocytes in both cases and controls.Figure 1. The percentage of granulocytes and lymphocytes in both cases and controls The authors do not declare any conflict of interest

Adherence and discontinuation rates in patients on Tecfidera™ (dimethyl fumarate): Long-term Canadian experience from the Biogen ONE™ support program

BackgroundTecfidera™ (dimethyl fumarate [DMF]; Biogen) is an oral disease-modifying therapy (DMT) indicated in Canada for the treatment of relapsing-remitting multiple sclerosis (MS). Biogen ONE™, an ongoing Canadian support program, facilitates access to DMF for patients with MS and maintains a database for the purposes of service provision. These data were utilized to assess adherence, persistence, discontinuations, and other outcomes between 2013 and 2021. MethodsThis non-interventional, retrospective study examined real-world use of DMF prescribed to patients with MS in Canada who were enrolled in the program and received their first dose between April 1, 2013, and June 30, 2021. Follow-up visits and laboratory monitoring occurred based on local standards and per the Canadian product monograph. For adherence and persistence assessments, patients must have had DMF dispensed by specialty pharmacies. Data were collected at patient enrollment, program exit, and throughout the duration of the program.The primary objective was to assess treatment adherence rates to DMF. Secondary objectives included treatment persistence rates, reasons for discontinuation, absolute lymphocyte counts (ALCs), and patient characteristics throughout the duration of the program. ResultsOverall, 12,608 DMF patients from the program were included between April 1, 2013, and June 30, 2021. At enrollment, mean (standard deviation [SD]) age was 40.6 (10.7) years and mean (SD) Expanded Disability Status Scale (EDSS) score was 2.2 (1.4). DMF was initiated as first-line DMT in 48.8% of patients.Of patients assessed (n = 6,848), 90.4% were adherent to DMF (based on medication possession ratio [MPR] ≥ 80%). Adherence (mean MPR) was marginally greater in DMT-naïve than switch patients, and in younger (< 40 years) than older (≥ 40 years) patients (both p < 0.001). Overall persistence on DMF at 24 months was 57.0%. Greater proportions of DMT-naïve patients persisted on DMF versus switch patients at all time points assessed. Persistence rates were comparable between female and male patients for up to 24 months, and between younger (< 40 years) and older (≥ 40 years) patients for up to 36 months.Older patients were more likely to discontinue for reasons related to lymphocytes (≥ 40 years, 16.1% vs. < 40 years, 6.1%) while efficacy reasons were reported with greater frequency in younger patients (≥ 40 years, 10.5% vs. < 40 years, 16.0%). Discontinuations due to gastrointestinal and flushing events occurred most frequently during the first month of treatment and decreased thereafter. Mean ALC decreased during the first year on treatment and subsequently plateaued.Over successive years, changes were observed in characteristics of patients starting on DMF, including decreases in EDSS score, age, and time since diagnosis. The proportion of DMT-naïve patients increased over the years (2013–2014, 26%–27%; 2018–2021, 62%–67%). ConclusionsHigh adherence was found in patients on DMF treatment within the Biogen support program with access to specialty pharmacies. The evolution of the patient population throughout the years suggests a shift towards earlier treatment. These real-world data may support the value of a support program in optimizing the management of patients on DMF treatment. Support programs provide personalized treatment monitoring, which can help minimize early discontinuations and improve adherence to treatment.

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.

Lymphopenia in Multiple Sclerosis patients treated with Ocrelizumab is associated with an effect on CD8 T cells

BackgroundIn the phase III, OPERA I and OPERA II, clinical trial lymphopenia was reported in 20.7% of relapsing–remitting multiple sclerosis (RRMS) patients taking Ocrelizumab (OCR). ObjectiveThe objective of this study was to investigate the effect of OCR on lymphocyte subtypes in MS patients with and without lymphopenia. MethodsRetrospective study comparing lymphocyte subtypes in OCR-treated MS patients with low (G1) and normal (G2) absolute lymphocyte count (ALC) at the six-month follow-up (cut-off: 1000 × 106/L). Mann Whitney U test was used to compare ALC, CD19, CD4 T, CD8 T and NK cell counts at baseline and at the six-month follow up between the two groups. A linear mixed model was applied to compare changes in ALC, and subset counts and proportions between patients with and without lymphopenia. We performed the same analyses in a subpopulation of naïve to treatment patients to exclude the possible influence of the previous disease modifying therapy (DMT) in the different kinetics observed between the two groups. Results: One hundred sixty-seven patients were included (G1, n = 34; G2, n = 133). At the six-month follow-up, compared with baseline, in the whole population we observed a significant reduction in ALC (p<0.0001), CD19 (p<0.0001) and CD8 T (p<0.0288) lymphocytes. We also found and increase in CD4/CD8 ratio after six months of treatment (p = 0.0098). G1 showed a lower ALC than G2 at baseline. At six months, mean ALC was 896.41 ± 156.25 × 106/L in G1 and 1909.9 ± 629.07 × 106/L in G2. CD4 and CD8 T cell mean counts were lower (p < 0.0001) in G1 than G2. At the linear mixed model analysis, we found a more pronounced increase in CD8 T percentage in G2 than G1 (p = 0.008). In the naïve to treatment group fifty patients were included. CD4 and CD8 T cell mean counts at six months were lower (p = 0.0074 and p = 0.0032, respectively) in G1 than G2. At the linear mixed model analysis, we found a more pronounced decrease of CD8 T cell count in G1 than G2 (p = 0.0103). Furthermore, we found an increase in CD8 T percentage in G2 whereas a profound decrease of CD8 T percentage was observed in G1 (p = 0.0052). After adjusting for confounders, significantly positive correlations were noted between ALC and both CD4 and CD8 T cell counts. Negative correlation was observed between ALC and CD4/CD8 ratio driven by low CD8 T cell counts. ConclusionOCR decreases ALC. Among T cells, the treatment predominantly impacts CD8 cells. However, CD8 T cell decrease was more pronounced in patients with lymphopenia. Further studies are needed to establish the relationship between the effect of OCR on ALC and CD8 T cells and its potential implication in the early clinical response and risk for viral infections.