Risk of cytomegalovirus infection and subsequent allograft failure after pancreas transplantation.

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

Association of Neutrophil-to-Lymphocyte Ratio and Absolute Lymphocyte Count With Clinical Outcomes in Advanced Breast Cancer in the MONARCH 2 Trial.

BACKGROUND: Established prognostic factors for treatment response to cyclin-dependent kinases 4 and 6 inhibitors are currently lacking. We aimed to investigate the relationship of pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) to abemaciclib outcomes. PATIENTS AND METHODS: This was a post hoc analysis of data from MONARCH 2, a phase III study of abemaciclib or placebo plus fulvestrant in hormone-receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer that progressed on endocrine therapy. Patients were divided into high and low categories based on baseline NLR (cutoff: 2.5) and ALC (cutoff: 1.5 × 109/L). The association of baseline NLR and ALC with progression-free survival (PFS) and overall survival (OS) was explored using Cox models and Kaplan-Meier estimates. Tumor response and safety were also examined. RESULTS: NLR and ALC data were available for 645 patients (abemaciclib: N = 426; placebo: N = 219). Low-baseline NLR or high-baseline ALC was consistently associated with positive PFS and OS trends; low-baseline NLR subgroups also showed trends for better response. The abemaciclib treatment effect against placebo was observed regardless of baseline NLR or ALC. Univariate analyses showed baseline NLR and ALC were prognostic of PFS and OS. Baseline NLR remained significant in the multivariate model (P < .0001). No unexpected differences in safety were observed by baseline NLR or ALC. CONCLUSION: Baseline NLR was independently prognostic of PFS and OS. Low-baseline NLR was associated with numerically better efficacy outcomes, but the benefit of adding abemaciclib to fulvestrant was similar irrespective of baseline NLR status.

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

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

The Changes in the Quantity of Lymphocyte Subpopulations during the Process of Sepsis.

Sepsis remains a global challenge, especially in low- and middle-income countries, where there is an urgent need for easily accessible and cost-effective biomarkers to predict the occurrence and prognosis of sepsis. Lymphocyte counts are easy to measure clinically, and a large body of animal and clinical research has shown that lymphocyte counts are closely related to the incidence and prognosis of sepsis. This review extensively collected experimental articles related to lymphocyte counts since the unification of the definition of sepsis. The article categorizes and discusses the relationship between absolute lymphocyte counts, intrinsic lymphocyte subsets, effector T-lymphocytes, B-lymphocytes, dendritic cells, and the incidence and prognosis of sepsis. The results indicate that comparisons of absolute lymphocyte counts alone are meaningless. However, in addition to absolute lymphocyte counts, innate lymphocyte subsets, effector T-cells, B-lymphocytes, and dendritic cells have shown certain research value in related studies.

Association Between Lymphopenia and Survival Outcomes in Esophageal Carcinoma Patients Receiving Combined Immunotherapy and Chemoradiotherapy.

BACKGROUND: To investigate the association between absolute lymphocyte count (ALC) nadir and survival outcomes in esophageal squamous cell carcinoma (ESCC) patients who received definitive chemoradiotherapy (CRT) combined with anti-PD-1 immunotherapy, as well as to explore clinical characteristics and dosimetric parameters that affect ALC nadir during CRT. PATIENTS AND METHODS: Patients with ESCC (n = 602) who underwent definitive CRT were analyzed, of whom 166 received combined anti-PD-1 immunotherapy and CRT. Changes in ALC and survival were compared between patients with and without immunotherapy. Propensity score matching (PSM) was performed to minimize the effects of confounding factors. Low ALC was defined as nadir of <0.33 × 103 cells/µL during CRT (top tertile). Univariate and multivariate logistic regression were used to identify predictors of low ALC nadir. RESULTS: Patients with immunotherapy had significantly higher ALC in the first 3 weeks during CRT and higher ALC nadir than those without. Overall survival was more favorable in patients with immunotherapy both before and after PSM. After a median follow-up of 12.1 months, patients with low ALC during CRT had a worse progression-free survival (PFS) (P = .026). In multivariate analysis, low ALC remained a significant prognostic factor for PFS. Planning target volume (PTV) and heart V5 were revealed to be independent predictors of low ALC. CONCLUSIONS: The addition of anti-PD-1 immunotherapy to definitive CRT could mitigate the decline of ALC during radiotherapy and might prolong survival. Low ALC nadir was correlated to worse PFS, larger PTV, and higher heart V5 in patients receiving combined immunotherapy and CRT.

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

BACKGROUND AIMS: The 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. METHODS: To 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. RESULTS: Median 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. CONCLUSIONS: sL-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.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Absolute lymphocyte count recovery following initial acute myelogenous leukemia therapy: Implications for adoptive cell therapy.

BACKGROUND: An adequate absolute lymphocyte count (ALC) is an essential first step in autologous chimeric antigen receptor (CAR) T-cell manufacturing. For patients with acute myelogenous leukemia (AML), the intensity of chemotherapy received may affect adequate ALC recovery required for CAR T-cell production. We sought to analyze ALC following each course of upfront therapy as one metric for CAR T-cell manufacturing feasibility in children and young adults with AML. PROCEDURE: ALC data were collected from an observational study of patients with newly diagnosed AML between the ages of 1 month and 21 years who received treatment between the years of 2006 and 2018 at one of three hospitals in the Leukemia Electronic Abstraction of Records Network (LEARN) consortium. RESULTS: Among 193 patients with sufficient ALC data for analysis, the median ALC following induction 1 was 1715 cells/µl (interquartile range: 1166-2388), with successive decreases in ALC with each subsequent course. Similarly, the proportion of patients achieving an ALC >400 cells/µl decreased following each course, ranging from 98.4% (190/193) after course 1 to 66.7% (22/33) for patients who received a fifth course of therapy. CONCLUSIONS: There is a successive decline of ALC recovery with subsequent courses of chemotherapy. Despite this decline, ALC values are likely sufficient to consider apheresis prior to the initiation of each course of upfront therapy for the majority of newly diagnosed pediatric AML patients, thereby providing a window of opportunity for T-cell collection for those patients identified at high risk of relapse or with refractory disease.

Predictive value of peripheral blood markers in soft tissue sarcoma patients treated with eribulin.

OBJECTIVE: eribulin, an anticancer agent that inhibits microtubule growth, along with trabectedin and pazopanib, has been approved for the treatment of advanced soft tissue sarcoma (STS). However, there has been no consensus on the optimal second-line therapy among these three agents following treatment failure with doxorubicin. Recently, the effects of eribulin on the tumor microenvironment and immunity have been reported in breast cancer, and peripheral blood immune markers have also been reported to be a predictor of eribulin efficacy, though this remains unverified in STS. We aimed to evaluate the predictive value of various peripheral blood immune markers in STS patients treated with eribulin. METHODS: we retrospectively reviewed the medical records of STS patients treated with eribulin and examined whether peripheral blood immune markers at different time points could be prognostic factors for STS patients treated with eribulin. RESULTS: several peripheral blood immune markers were significantly associated with progression-free survival (PFS), specifically neutrophil-to-lymphocyte ratio (NLR) prestart (NLR before the initial administration of eribulin) (P = 0.019) and absolute lymphocyte count (ALC)8D (ALC on Day 8 of the first administration of eribulin) (P = 0.037). NLR prestart (P = 0.001) was significantly associated with overall survival. The combination of NLR prestart and ALC8D determined the PFS of STS patients treated with eribulin. CONCLUSIONS: the combined indicator of low NLR prestart and high ALC8D predicted the survival of patients treated with eribulin as well as the histology of L-sarcoma. Though further validation was needed, this finding would provide valuable prognostic factor that help treatment decision in the absence of consensus on the optimal second-line therapy following doxorubicin treatment in STS patients.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Outcomes of blinatumomab based therapy in children with relapsed, persistent, or refractory acute lymphoblastic leukemia: a multicenter study focusing on predictors of response and post-treatment immunoglobulin production.

The management of Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (R/R ALL) remains challenging. Incorporating blinatumomab in R/R ALL treatment has shown encouraging results. We describe the outcome and predictors of response in children receiving blinatumomab as a bridge to definitive therapy. Immunoglobulin (Ig) G and viral serology before and after therapy were evaluated. Thirty-three patients that failed standard first-line treatments due to relapsed ALL (n = 22), persistent minimal residual disease (MRD) (n = 8), or refractory disease (n = 3) received blinatumomab. Grade 2 toxicity occurred in 27.2% of patients. MRD remission (<0.01%) was achieved in 72.7% of patients. Pre-blinatumomab absolute lymphocyte count (ALC) and MRD/ALC ratio significantly associated with MRD-response. Patients with t(1;19) translocation had lower response rate, compared to all other cytogenetic categories (p = 0.013). One-year event-free survival (EFS) and overall survival (OS) were 69.2% and 79.7%, respectively. Analysis of OS and EFS showed pre-blinatumomab MRD level, ALC, MRD/ALC ratio, t(1;19), and post-blinatumomab MRD remission associated with survival. Following blinatumomab, 83% (15/18) of tested patients had low IgG levels. IgG seronegative status was observed in 83% (12/15) for varicella zoster, 35% (6/17) for herpes zoster, 18% (3/17) for cytomegalovirus, and 26% (5/17) for Epstein Barr virus. Blinatumomab produced encouraging results in children with R/R ALL and low disease burden bridging to definitive therapy. Incorporating baseline genetics and biomarkers may help identify subgroups likely to be responsive/resistant to therapy. Viral serological testing pre- and post-blinatumomab is recommended to optimize supportive and preemptive therapy.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2049936 .

[Antithymocyte globulin for graft-versus-host disease prophylaxis, past, present and future].

Antithymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis has been demonstrated for chronic GVHD inhibition by a series of randomized control trials. The optimal dose of ATG remained unestablished; however, the recommended dose of ATG by the European Group for Blood and Marrow Transplantation has recently decreased. While a lower ATG dose has been used in Japan, ATG usage is recommended in peripheral blood stem cell transplantation or human leukocyte antigens (HLA) 1-locus mismatched bone marrow transplantation with myeloablative conditioning from the nation-wide retrospective studies showing that ATG inhibited chronic GVHD and improved GVHD-free, relapse-free survival. The association of absolute lymphocyte counts (ALC) before ATG administration with transplant outcomes has been reported, which suggests a possible strategy to individualize the ATG dose according to ALC before ATG. Recent studies compared the transplant outcomes using ATG and post-transplant cyclophosphamide, which has rapidly spread in haploidentical transplantation; however, further studies are needed to establish those positioning in HLA-matched/mismatched transplantation.

High lymphocyte population-related predictive factors for a long-term response in non-small cell lung cancer patients treated with pemetrexed: a retrospective observational study.

BACKGROUND: Regimens combining pemetrexed (PEM) and immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed death-ligand 1 (PD-L1) are widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSq-NSCLC). Recently, PEM was shown to induce immunogenic cell death (ICD) and to enhance immune-regulatory genes. Some patients demonstrate an extremely long-term response to PEM. It is possible that the continued response in these patients is dependent on not only the pharmacological induction of cytotoxic cell death but also antitumor immunity. However, factors that can predict outcomes associated with long-term PEM administration using blood test results have not yet been elucidated. We investigated the clinical characteristics and predictive factors in patients with advanced NSq-NSCLC who underwent long-term PEM maintenance therapy. METHODS: In total, 504 patients with advanced NSq-NSCLC who received PEM combination therapy/monotherapy (n = 414) or paclitaxel (PTX) combination therapy (n = 90) between January 2010 and November 2019 were recruited; 381 patients were retained for the final analysis. Patients treated with PEM (n = 301) were divided into subgroups according to the total cycles of PEM (≥ 17 [n = 25] for the long-term administration group and ≤ 16 [n = 276] for the intermediate/short-term group) and compared with another population (n = 80) treated with PTX combination regimen. We investigated clinical features and predictive biomarkers, focusing on immune-regulatory factors, absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), and PD-1 and PD-L1 expression, to predict long-term response to PEM. RESULTS: The long-term PEM administration group exhibited a higher ALC and a lower NLR than the shorter-term group did. Both these markers displayed greater association with progression-free survival and overall survival in the PEM combination therapy group than in the PTX combination therapy group. Increased PD-1 lymphocytes were associated with the long-term PEM response group, as PD-L1 expression in tumors was associated with a high incidence of immune-related adverse effects following ICI administration. CONCLUSIONS: ALC, NLR, and PD-1 expression are PEM-mediated predictive biomarkers that are indirectly related to tumor immunity and can provide useful predictive information on the long-term response to PEM in patients with NSq-NSCLC.

Normal Absolute Monocyte Count in Combination with Normal/High Absolute Lymphocyte Count at the Time of Relapse is Associated with Improved Survival in Patients with Early Relapsed Acute Myeloid Leukemia.

This study aimed to examine the prognostic significance of peripheral absolute monocyte count (AMC) in combination with absolute lymphocyte count (ALC) at the time of relapse in a cohort of 57 patients with early relapsed (first complete remission <12 months) acute myeloid leukemia (AML). Both univariate and multivariate Cox proportional hazard regression analyses revealed that normal AMC in combination with normal/high ALC (versus low/high AMC in combination with low ALC) was significantly associated with improved OS. We concluded that the combination of AMC and ALC could be used as a prognostic marker for survival outcomes in early relapsed AML.

The predictive value of absolute lymphocyte counts on tumor progression and pseudoprogression in patients with glioblastoma.

BACKGROUND: Differentiating true glioblastoma multiforme (GBM) from pseudoprogression (PsP) remains a challenge with current standard magnetic resonance imaging (MRI). The objective of this study was to explore whether patients' absolute lymphocyte count (ALC) levels can be utilized to predict true tumor progression and PsP. METHODS: Patients were considered eligible for the study if they had 1) GBM diagnosis, 2) a series of blood cell counts and clinical follow-ups, and 3) tumor progression documented by both MRI and pathology. Data analysis results include descriptive statistics, median (IQR) for continuous variables and count (%) for categorical variables, p values from Wilcoxon rank sum test or Fisher's exact test for comparison, respectively, and Kaplan-Meier analysis for overall survival (OS). OS was defined as the time from patients' second surgery to their time of death or last follow up if patients were still alive. RESULTS: 78 patients were included in this study. The median age was 56 years. Median ALC dropped 34.5% from baseline 1400 cells/mm3 to 917 cells/mm3 after completion of radiation therapy (RT) and temozolomide (TMZ). All study patients had undergone surgical biopsy upon MRI-documented progression. 37 had true tumor progression (47.44%) and 41 had pseudoprogression (52.56%). ALC before RT/TMZ, post RT/TMZ and at the time of MRI-documented progression did not show significant difference between patients with true progression and PsP. Although not statistically significant, this study found that patients with true progression had worse OS compared to those with PsP (Hazard Ratio [HR] 1.44, 95% CI 0.86-2.43, P = 0.178). This study also found that patients with high ALC (dichotomized by median) post-radiation had longer OS. CONCLUSION: Our results indicate that ALC level in GBM patients before or after treatment does not have predictive value for true disease progression or pseudoprogression. Patients with true progression had worse OS compared to those who had pseudoprogression. A larger sample size that includes CD4 cell counts may be needed to evaluate the PsP predictive value of peripheral blood biomarkers.

High lymphocyte counts before antithymocyte globulin administration predict acute graft-versus-host disease.

Antithymocyte globulin (ATG) reduces severe acute and chronic graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (PBSCT). However, risk factors for severe acute GVHD in PBSCT using ATG remain to be determined. We conducted a single-center, retrospective study to analyze the association of acute GVHD requiring systemic corticosteroid (SC-aGVHD) with absolute lymphocyte counts (ALC) before the administration of ATG or conditioning in 53 patients with HLA-matched PBSCT using low-dose thymoglobulin (2 mg/kg) after myeloablative conditioning. The cumulative incidence of SC-aGVHD was 17.0% and ALC before ATG were significantly higher in patients with SC-aGVHD compared to that in patients without it (median, 0.15 × 109/L vs 0.06 × 109/L, P = 0.047). The cumulative incidence of SC-aGVHD was significantly higher in patients with high ALC before ATG (≥ 0.15 × 109/L) than in those with low ALC (38.5% vs 10.0%, P = 0.016). Non-relapse mortality (NRM) was also significantly higher in the high ALC before ATG group than the low ALC before ATG group (2-year NRM: 23.9% vs 6.0%, P = 0.048), leading to worse survival (2-year overall survival: 69.2% vs 83.5%, P = 0.039). Our study suggested that high ALC before ATG is a risk factor for SC-aGVHD.

Extracellular vesicles and their associated miRNAs as potential prognostic biomarkers in chronic lymphocytic leukemia.

PURPOSE OF REVIEW: Many prognostic and predictive biomarkers have been proposed for chronic lymphocytic leukaemia (CLL). Here, we aim to discuss the evidence showing a prognostic potential for extracellular vesicles (EV) and their associated microRNAs (miRNAs). RECENT FINDINGS: EV are produced by several cells in the body as a physiological event; however, there is evidence suggesting that an elevated EV concentration is present in the circulation of CLL patients. Moreover, some studies have associated EV concentration with advanced Rai stage and unmutated CLL while others have demonstrated its potential as an independent prognostic factor for TTFT and OS. Finally, some studies have shown that CLL EV shared some dysregulated microRNAs with CLL cells and plasma. On the other hand, it was found that CLL EV has a distinctive microRNA expression profile. Until now, EV-associated miR-155 is the most studied miRNA. Despite methodological diversity and limitations in study design, unanimity in CLL EV concentration behaviour and miRNA content has been found.

Association of the areas over and under the lymphocyte curve with cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: We retrospectively compared the impact of the areas over and under the lymphocyte curve (L_AOC vs L_AUC) on cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Among 394 consecutive patients who underwent their first allogeneic HSCT at our center between 2007 and 2018, 301 patients met the inclusion criteria. L_AOC was calculated as the area over the lymphocyte curve during lymphopenia (absolute lymphocyte count [ALC] <700/µL). We calculated L_AOC and L_AUC from day 0 to day 15 (L_AOC15, L_AUC15) and from day 0 to day 30 (L_AOC30, L_AUC30). RESULTS: CMV antigenemia was defined as more than 3 cells/2 slides by the C10/11 method and detected in 204 cases (CMV reactivation) at a median of 39 days after HSCT. Although there were significant differences in L_AOC15, L_AOC30, L_AUC15, and L_AUC30 between patients with and without CMV reactivation, there was no difference in accuracy for predicting CMV reactivation between L_AOC and L_AUC. In a multivariate analysis, L_AOC15 and L_AUC15 were each identified as independent predictive factors for CMV reactivation, along with advanced age and CMV serostatus. However, ALC at day 14 or day 21 was as accurate as area-based indexes such as L_AOC15 and L_AUC15. L_AOC15 and L_AUC15 were significantly associated with longer duration of anti-CMV antiviral therapy while ALC was not. CONCLUSIONS: L_AOC15 and L_AUC15 had similar impacts on CMV reactivation. Although these area-based indexes were not superior to ALC for predicting CMV reactivation, they might predict patients who need longer duration of antiviral therapy more accurately.

Analysis of absolute lymphocyte count in patients with COVID-19.

INTRODUCTION: Symptoms of COVID-19 vary in severity and presentation. When admitting patients to the hospital, it is desirable to isolate patients with COVID-19 from those without the disease. However, reliably identifying patients with COVID-19 in the emergency department before hospital admission is often limited by the speed and availability of testing. Previous studies determined a low lymphocyte count is commonly found in patients with COVID-19. We sought to explore the sensitivity of absolute lymphocyte count in patients presenting to the emergency department requiring subsequent hospitalization who were found to have COVID-19. METHODS: A retrospective chart review was performed on 312 patients with laboratory-confirmed COVID-19 who were admitted to the hospital from the emergency department. The absolute lymphocyte count for these patients was used to calculate sensitivities at various cut-off values. The relationships between absolute lymphocyte count and variables, including age, sex, need for intubation, and mortality, were also explored. RESULTS: Cut-off values for absolute lymphocyte count ranged from 1.1 K/uL to 2.0 K/uL, with sensitivities of 72% and 94%, respectively. Additionally, lower mean absolute lymphocyte counts were identified in males, patients who required intubation, and patients who died. CONCLUSION: Knowing the sensitivity of absolute lymphocyte count in patients with COVID-19 may help identify patients who are unlikely to have the disease. Additionally, absolute lymphocyte count can be used as a marker of disease severity in patients with COVID-19.