Metabolic tumor volume from baseline [18 F]FDG PET/CT at diagnosis improves the IPI stratification in patients with diffuse large B-cell lymphoma.

PURPOSE: Although several different parameters of PET/CT were reported to be predictive of survival in DLBCL, the best parameter remains to be elucidated and whether it could improve the risk stratification of IPI in patients with DLBCL. PROCEDURES: 262 DLBCL patients including in the training and validation cohort were retrospectively analyzed in this study. RESULTS: Among different parameters, MTV was identified as the optimal prognostic parameter with a maximum area under the curve (AUC) of 0.652 ± 0.112 than TLG and SDmax (0.645 ± 0.113 and 0.600 ± 0.117, respectively). Patients with high MTV were associated with inferior PFS (p < 0.001 and p = 0.021, respectively) and OS (p < 0.001 and p < 0.001, respectively) in both the training and validation cohort. The multivariate analysis revealed that high MTV was an unfavorable factor for PFS (relative ratio [RR], 2.295; 95% confidence interval [CI], 1.457-3.615; p < 0.01) and OS (RR, 2.929; 95% CI 1.679-5.109; p < 0.01) independent of IPI. CONCLUSIONS: Further analysis showed MTV could improve the risk stratification of IPI for both PFS and OS (p < 0.01 and p < 0.01, respectively). In conclusion, our study suggests that MTV was an optimal prognostic parameter of PET/CT for survival and it could improve the risk stratification of IPI in DLBCL, which may help to guide treatment in clinical trial.

HVEM in acute lymphocytic leukemia facilitates tumour immune escape by inhibiting CD8+ T cell function.

PURPOSE: Leukaemia remains a major contributor to global mortality, representing a significant health risk for a substantial number of cancer patients. Despite notable advancements in the field, existing treatments frequently exhibit limited efficacy or recurrence. Here, we explored the potential of abolishing HVEM (herpes virus entry mediator, TNFRSF14) expression in tumours as an effective approach to treat acute lymphoblastic leukaemia (ALL) and prevent its recurrence. METHODS: The clinical correlations between HVEM and leukaemia were revealed by public data analysis. HVEM knockout (KO) murine T cell lymphoblastic leukaemia cell line EL4 were generated using CRISPR-Cas9 technology, and syngeneic subcutaneous tumour models were established to investigate the in vivo function of HVEM. Immunohistochemistry (IHC), RNA-seq and flow cytometry were used to analyse the tumour immune microenvironment (TIME) and tumour draining lymph nodes (dLNs). Immune functions were investigated by depletion of immune subsets in vivo and T cell functional assays in vitro. The HVEM mutant EL4 cell lines were constructed to investigate the functional domain responsible for immune escape. RESULTS: According to public databases, HVEM is highly expressed in patients with ALL and acute myeloid leukemia (AML) and is negatively correlated with patient prognosis. Genetic deletion of HVEM in EL4 cells markedly inhibited tumour progression and prolonged the survival of tumour-bearing mice. Our experiments proved that HVEM exerted its immunosuppressive effect by inhibiting antitumour function of CD8+ T cell through CRD1 domain both in vivo and in vitro. Additionally, we identified a combination therapy capable of completely eradicating ALL tumours, which induces immune memory toward tumour protection. CONCLUSIONS: Our study reveals the potential mechanisms by which HVEM facilitates ALL progression, and highlights HVEM as a promising target for clinical applications in relapsed ALL therapy.

Prediction significance of autophagy-related genes in survival probability and drug resistance in diffuse large B-cell lymphoma.

BACKGROUND/AIMS: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, has significant prognostic heterogeneity. This study aimed to generate a prognostic prediction model based on autophagy-related genes for DLBCL patients. METHODS: Utilizing bioinformatics techniques, we analyzed the clinical information and transcriptome data of DLBCL patients from the Gene Expression Omnibus (GEO) database. Through unsupervised clustering, we identified new autophagy-related molecular subtypes and pinpointed differentially expressed genes (DEGs) between these subtypes. Based on these DEGs, a prognostic model was constructed using Cox and Lasso regression. The effectiveness, accuracy, and clinical utility of this prognostic model were assessed using numerous independent validation cohorts, survival analyses, receiver operating characteristic (ROC) curves, multivariate Cox regression analysis, nomograms, and calibration curves. Moreover, functional analysis, immune cell infiltration, and drug sensitivity analysis were performed. RESULTS: DLBCL patients with different clinical characterizations (age, molecular subtypes, ECOG scores, and stages) showed different expression features of autophagy-related genes. The prediction model was constructed based on the eight autophagy-related genes (ADD3, IGFBP3, TPM1, LYZ, AFDN, DNAJC10, GLIS3, and CCDC102A). The prognostic nomogram for overall survival of DLBCL patients incorporated risk level, stage, ECOG scores, and molecular subtypes, showing excellent agreement between observed and predicted outcomes. Differences were noted in the proportions of immune cells (native B cells, Treg cells, CD8+ T cell, CD4+ memory activated T cells, gamma delta T cells, macrophages M1, and resting mast cells) between high-risk and low-risk groups. LYZ and ADD3 exhibited correlations with drug resistance to most chemotherapeutic drugs. CONCLUSIONS: This study established a novel prognostic assessment model based on the expression profile of autophagy-related genes and clinical characteristics of DLBCL patients, explored immune infiltration and predicted drug resistance, which may guide precise and individualized immunochemotherapy regimens.

Value of blood oxygenation level-dependent magnetic resonance imaging in early evaluation of the response and prognosis of esophageal squamous cell carcinoma treated with definitive chemoradiotherapy: a preliminary study.

BACKGROUND: To find a useful hypoxia non-invasive biomarker for evaluating early treatment response and prognosis to definitive chemoradiotherapy (dCRT) in patients with esophageal squamous cell carcinoma (ESCC), using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). METHODS: The R2* values were obtained pre- and 2-3 weeks post-dCRT in 28 patients with ESCC using BOLD MRI. Independent samples t-test (normality) or Mann-Whitney U test (non-normality) was used to compare the differences of R2*-related parameters between the complete response (CR) and the non-CR groups. Diagnostic performance of parameters in predicting response was tested with receiver operating characteristic (ROC) curve analysis. The 3-year overall survival (OS) was evaluated using Kaplan Meier curve, log rank test, and Cox proportional hazards regression analysis. RESULTS: The post-R2*, ∆R2*, and ∆%R2* in the CR group were significantly higher than those in the non-CR group (P = 0.002, 0.003, and 0.006, respectively). The R2*-related parameters showed good prediction of tumor response, with AUC ranging from 0.813 to 0.829. The 3-year OS rate in patients with ∆R2* >-7.54 s- 1 or CR were significantly longer than those with ∆R2* ≤ -7.54 s- 1 (72.37% vs. 0.00%; Hazard ratio, HR = 0.196; 95% confidence interval, 95% CI = 0.047-0.807; P = 0.024) or non-CR (76.47% vs. 29.27%; HR = 0.238, 95% CI = 0.059-0.963; P = 0.044). CONCLUSIONS: The preliminary results demonstrated that the R2* value might be a useful hypoxia non-invasive biomarker for assessing response and prognosis of ESCC treated with dCRT. BOLD MRI might be used as a potential tool for evaluating tumor oxygenation metabolism, which is routinely applied in clinical practice and beneficial to clinical decision-making. A large sample size was needed for further follow-up studies to confirm the findings.

Selenium Ameliorated Oxidized Fish Oil-Induced Lipotoxicity via the Inhibition of Mitochondrial Oxidative Stress, Remodeling of Usp4-Mediated Deubiquitination, and Stabilization of Pparα.

Aims: Studies demonstrated that oxidized fish oil (OFO) promoted oxidative stress and induced mitochondrial dysfunction and lipotoxicity, which attenuated beneficial effects of fish oil supplements in the treatment of nonalcoholic fatty liver disease (NAFLD). The current study was performed on yellow catfish, a good model to study NAFLD, and its hepatocytes to explore whether selenium (Se) could alleviate OFO-induced lipotoxicity via the inhibition of oxidative stress and determine its potential mechanism. Results: The analysis of triglycerides content, oxidative stress parameters, and histological and transmission electronic microscopy observation showed that high dietary Se supplementation alleviated OFO-induced lipotoxicity, oxidative stress, and mitochondrial injury and dysfunction. RNA-sequencing and immunoblotting analysis indicated that high dietary Se reduced OFO-induced decline of peroxisome-proliferator-activated receptor alpha (Pparα) and ubiquitin-specific protease 4 (Usp4) protein expression. High Se supplementation also alleviated OFO-induced reduction of thioredoxin reductase 2 (txnrd2) messenger RNA (mRNA) expression level and activity. The txnrd2 knockdown experiments revealed that txnrd2 mediated Se- and oxidized eicosapentaenoic acid (oxEPA)-induced changes of mitochondrial reactive oxygen species (mtROS) and further altered Usp4 mediated-deubiquitination and stabilization of Pparα, which, in turn, modulated mitochondrial fatty acid ß-oxidation and metabolism. Mechanistically, Usp4 deubiquitinated Pparα and ubiquitin-proteasome-mediated Pparα degradation contributed to oxidative stress-induced mitochondrial dysfunction. Innovation: These findings uncovered a previously unknown mechanism by which Se and OFO interacted to affect lipid metabolism via the Txnrd2-mtROS-Usp4-Pparα pathway, which provides the new target for NAFLD prevention and treatment. Conclusion: Se ameliorated OFO-induced lipotoxicity via the inhibition of mitochondrial oxidative stress, remodeling of Usp4-mediated deubiquitination, and stabilization of Pparα. Antioxid. Redox Signal. 40, 433-452.

Changing epidemiology, microbiology and mortality of bloodstream infections in patients with haematological malignancies before and during SARS-CoV-2 pandemic: a retrospective cohort study.

OBJECTIVE: This study was to explore the changes in bacterial bloodstream infection (BSI) in patients with haematological malignancies (HMs) before and during SARS-CoV-2 pandemic. DESIGN: Retrospective cohort study between 2018 and 2021. SETTING: The largest haematological centre in southern China. RESULTS: A total of 599 episodes of BSI occurring in 22 717 inpatients from January 2018 to December 2021 were analysed. The frequencies of the total, Gram-negative and Gram-positive BSI before and during the pandemic were 2.90% versus 2.35% (p=0.011), 2.49% versus 1.77% (p<0.001) and 0.27% versus 0.44% (p=0.027), respectively. The main isolates from Gram-negative or Gram-positive BSI and susceptibility profiles also changed. The 30-day mortality caused by BSI was lower during the pandemic (21.1% vs 14.3%, p=0.043). Multivariate analysis revealed that disease status, pulmonary infection and shock were independent predictors of 30-day mortality. CONCLUSION: Our data showed that the incidence of total and Gram-negative organisms BSI decreased, but Gram-positive BSI incidence increased in patients with HMs during the pandemic along with the changes of main isolates and susceptibility profiles. Although the 30-day mortality due to BSI was lower during the pandemic, the new infection prevention strategy should be considered for any future pandemics.

Clinical factors of PICC-RVT in cancer patients: a meta-analysis.

PURPOSE: There is a lack of studies that systematically evaluate the clinical factors of PICC-RVT such as treatment, tumor stage, metastasis, and chemotherapy drugs in cancer patients. This study, therefore, aims to evaluate the clinical factors of catheter-related venous thrombosis in cancer patients with indwelling PICC to provide a basis for the clinical prevention and reduction of thrombosis. METHODS: Relevant studies were retrieved from major databases (PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang Data, and China Biology Medicine disc (CMB)) and searched from their earliest available dates until July 2022. If two or more studies had the same outcome, a meta-analysis using RevMan 5.4.1 was performed. This systematic review was registered at PROSPERO (number CRD42022358426). RESULTS: A total of 19 articles involving 19,824 patients were included for quantitative analysis. Meta-analysis of these studies indicated that a history of chemotherapy, tumor type, tumor stage, presence or absence of metastasis, and use of fluorouracil, etoposide, platinum drugs, and taxane were all risk factors for PICC catheter thrombosis in cancer patients. CONCLUSION: In clinical PICC catheter thrombosis prevention, patients with the above characteristics should be watched more closely than other patients, as they have a higher risk for PICC catheter thrombosis. Based on the present evidence at hand, radiotherapy cannot be considered to be related to the formation of PICC-RVT in cancer patients.

Stem cell mobilization in multiple myeloma: challenges, strategies, and current developments.

Among hematological malignancies, multiple myeloma (MM) represents the leading indication of autologous hematopoietic stem cell transplantation (auto-HCT). Auto-HCT is predominantly performed with peripheral blood stem cells (PBSCs), and the mobilization and collection of PBSCs are essential steps for auto-HCT. Despite the improved success of conventional methods with the incorporation of novel agents for PBSC mobilization in MM, mobilization failure is still a concern. The current review comprehensively summarizes various mobilization strategies for mobilizing PBSCs in MM patients and the evolution of these strategies over time. Moreover, existing evidence substantiates that the mobilization regimen used may be an important determinant of graft content. However, limited data are available on the effects of graft characteristics in patient outcomes other than hematopoietic engraftment. In this review, we discussed the effect of graft characteristics on clinical outcomes, mobilization failure, factors predictive of poor mobilization, and potential mobilization regimens for such patients.

Glycophagy mediated glucose-induced changes of hepatic glycogen metabolism via OGT1-AKT1-FOXO1Ser238 pathway.

Glycophagy is the autophagy degradation of glycogen. However, the regulatory mechanisms for glycophagy and glucose metabolism remain unexplored. Herein, we demonstrated that high-carbohydrate diet (HCD) and high glucose (HG) incubation induced glycogen accumulation, protein kinase B (AKT)1 expression and AKT1-dependent phosphorylation of forkhead transcription factor O1 (FOXO1) at Ser238 in the liver tissues and hepatocytes. The glucose-induced FOXO1 phosphorylation at Ser238 prevents FOXO1 entry into the nucleus and the recruitment to the GABA(A) receptor-associated protein like 1 (gabarapl1) promoter, reduces the gabarapl1 promoter activity, and inhibits glycophagy and glucose production. The glucose-dependent O-GlcNAcylation of AKT1 by O-GlcNAc transferase (OGT1) enhances the stability of AKT1 protein and promotes its binding with FOXO1. Moreover, the glycosylation of AKT1 is crucial for promoting FOXO1 nuclear translocation and inhibiting glycophagy. Our studies elucidate a novel mechanism for glycophagy inhibition by high carbohydrate and glucose via OGT1-AKT1-FOXO1Ser238 pathway in the liver tissues and hepatocytes, which provides critical insights into potential intervention strategies for glycogen storage disorders in vertebrates, as well as human beings.

Klf4-Sirt3/Pparα-Lcad pathway contributes to high phosphate-induced lipid degradation.

BACKGROUND: Phosphorus commonly reduces lipid deposition in the vertebrates. However, the underlying mechanisms involved in the process remain unclear. METHODS: Yellow catfish were given three experimental diets with dietary phosphate levels of 3.22, 6.47 and 7.99 g Pi kg- 1, respectively, for 8 weeks. The contents of triglyceride, non-esterified free fatty acids, adenosine triphosphate, nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide, enzymatic activities, mRNA and protein expression were determined in the intestinal tissues. Hematoxylin and eosin, Oil Red O staining, and transmission electron microscope were performed for intestinal tissues. Primary intestinal epithelial cells were isolated from yellow catfish intestine. Western blot analysis, Immunoprecipitation assays, Immunofluorescence staining, and RNA extraction and quantitative real-time PCR were decided. Luciferase reporter assays and electrophoretic mobility shift assay were used to evaluate the function of Sirt3, PPARα and Lcad promoters. RESULTS: High dietary phosphate intake activated intestinal phosphate absorption and excretion, and reduced lipid deposition through increasing lipolysis in the intestine. Moreover, phosphate incubation increased the mRNA and protein expression of krüppel like factor 4 (klf4), silent mating-type information regulation 2 homolog 3 (sirt3), peroxisome proliferator activated receptor alpha (pparα) and long chain acyl-CoA dehydrogenase (lcad) in the intestinal epithelial cells (IECs), and klf4 knockdown attenuated the phosphate-induced increase of protein levels of Sirt3, Pparα and Lcad. Further investigation found that Klf4 overexpression increased the activity of sirt3 and pparα promoters, which in turn reduced the acetylation and protein level of Lcad. CONCLUSION: Dietary Pi excess induced lipid degradation by the activation of the Klf4-Sirt3/Pparα-Lcad pathway in the intestine and primary IECs. Video Abstract.

Haplo-Peripheral Blood Stem Cell Plus Cord Blood Grafts for Hematologic Malignancies Might Lead to Lower Relapse Compared with Haplo-Peripheral Blood Stem Cell Plus Bone Marrow Grafts.

To compare the outcomes between peripheral blood stem cell (PBSC)+cord blood and PBSC+bone marrow (BM) grafts in the setting of haploidentical donor (HID) transplantation, 110 patients were enrolled in this retrospective study, including 54 recipients of haplo-PBSC+cord transplants and 56 recipients of haplo-PBSC+BM transplants. Chimerism analyses revealed that by day 30 post-transplantation, 94.3% of surviving patients in the haplo-PBSC+cord group had achieved full haploidentical chimerism and 5.7% had <10% cord chimerism, whereas 100% of surviving patients in the haplo-PBSC+BM group had achieved full donor chimerism. The cumulative incidence of platelet engraftment at 30 days was 92.6% in the haplo-PBSC+cord group versus 89.3% in the haplo-PBSC+BM group (P =.024), that of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 31.5% versus 48.2% (P =.060), and 1-year relapse was 13.0% versus 25.0% (P =.027), nonrelapse mortality was 9.3% versus 12.5% (P =.76), disease-free survival (DFS) was 77.7% versus 62.5% (P =.028), and overall survival (OS) was 81.4% versus 69.6% (P =.046). Multivariate analysis identified haplo-PBSC+cord transplantation as a protective factor for relapse (hazard ratio [HR], .31; P =.007), DFS (HR, .40; P =.007), and OS (HR, .44; P =.016). Overall, haplo-PBSC+cord transplantation led to faster platelet engraftment, lower relapse, and superior DFS and OS compared with haplo-PBSC+BM transplantation and thus might be a better transplant mode in the setting of HID transplantation.

CD43 is an adverse prognostic factor in newly diagnosed multiple myeloma.

Currently, the expression pattern and prognostic value of CD43 expression in multiple myeloma (MM) remain unknown. 109 newly diagnosed MM patients were recruited and CD43 expression was determined by multiparameter flow cytometry, of which 77 (70.6%) were CD43 positive. Patients with positive CD43 expression were more likely to present with, hemoglobin < 85 g/L (p = 0.008), International Staging System (ISS) stage III (p = 0.044), 13q14 deletion (p = 0.034) and more monoclonal plasma cells (p = 0.003). Patients with CD43 positive had significantly poor treatment response (p = 0.021), progression-free survival (PFS) (p = 0.012), and overall survival (OS) (p = 0.023) than those without CD43. The poorer prognosis of CD43-positive patients was retained in multivariate analysis (p = 0.005 for PFS; p = 0.013 for OS). Our study indicated that CD43 was an independent adverse prognostic factor in multiple myeloma.

Mitochondrial oxidative stress mediated Fe-induced ferroptosis via the NRF2-ARE pathway.

Ferroptosis is a regulated form of cell death induced by iron (Fe)-dependent lipid peroxidation. At present, the underlying molecular mechanisms remain elusive. Herein, we hypothesized that mitochondria and the NRF2 (transcription factor nuclear factor E2-related factor 2) are potential mediators of ferroptosis, considering their well-established involvement in the oxidative stress pathway. We found that a high iron diet increased hepatic iron content and promoted glutathione (GSH) depletion, lipid peroxidation and oxidative stress. Dietary iron overload also decreased mRNA and protein expression levels of glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11), and increased mRNA and protein expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), which are all markers of ferroptosis. Consistent with ferroptosis, iron overload promoted lipid peroxidation and the generation of mitochondrial reactive oxygen species (ROS), and decreased the mitochondrial membrane potential (MMP). Pre-treatment with deferoxamine mesylate (DFO, an iron chelator) alleviated ROS generation and lipid peroxidation, indicating a causative link between iron overload and lipid peroxidation. Suppression of mitochondrial oxidative stress attenuated ferroptosis. Experiments with HEK293T cells revealed that Fe-induced ferroptosis involved direct inhibition of NRF2 binding to antioxidant response elements (AREs) within the promoters of the gpx4 and slc7a11 genes, which in turn induced transcriptional silencing. In conclusion, our study provided a direct link between mitochondrial oxidative stress and ferroptosis via the NRF2-ARE pathway.

LINC00908 Promotes Diffuse Large B-Cell Lymphoma Development by Down-Regulating miR-671-5p.

INTRODUCTION: Emerging evidence has revealed that long noncoding RNA (lncRNA) play important role in almost all kinds of human cancers. LINC00908 has been reported to be involved in the development of prostate cancer, colorectal cancer and gastric cancer which was functioned as an oncogene. However, the potential biology role and molecular mechanism of LINC00908 in diffuse large B-cell lymphoma are still unclear. METHODS: LINC00908 and miR-671-5p expression were evaluated in DLBCL tissues and cell lines using RT-qPCR. CCK-8 and transwell assay were used to analyze the in vitro role of LINC00908 in DLBCL progression. The xenograft model was used to explore the in vivo role of LINC00908 in DLBCL growth. The physical interaction between LINC00908 and miR-671-5p was confirmed using bioinformatics analysis and a dual luciferase assay, RIP and RNA pull down. RESULTS: The expression of LINC00908 was markedly up-regulated in diffuse large B-cell lymphoma tissues and cell lines, and the decreased expression of LINC00908 significantly inhibited diffuse large B-cell lymphoma cell proliferation and invasion. Then, we revealed that LINC00908 directly interacted with miR-671-5p, which was down-regulated in diffuse large B-cell lymphoma cells and highly expressed with LINC00908 knockdown. Moreover, luciferase reporter assays and RNA immunoprecipitation (RIP) assay further proved that miR-671-5p is a direct target of LINC00908 in diffuse large B-cell lymphoma cells. Rescue experiments were also performed, and we confirmed that LINC00908 acts as an oncogene role in diffuse large B-cell lymphoma through miR-671-5p. Finally, the influence of LINC00908 silence significantly inhibited diffuse large B-cell lymphoma growth in vivo. CONCLUSION: LINC00908 promotes malignancy of diffuse large B-cell lymphoma through regulating miR-671-5p.

Partial immunoparesis contributes to risk of early infections in patients with multiple myeloma.

BACKGROUND: Partial immunoparesis, which means at least two suppressed uninvolved immunoglobulins (Igs), had been reported to be associated with poor prognosis in patients with multiple myeloma (MM), but the impact on early infections remains unknown. The purpose of our study was to determine the prognostic implications of partial immunoparesis on early grade ≥3 infections in patients with MM. METHODS: Herein we retrospectively analyzed the clinical data of 123 MM patients between 2012 and 2020 at Nanfang Hospital. All patients received bortezomib-based regimens. The relationship between early grade ≥3 infections and partial immunoparesis was investigated using Cox regression analysis. RESULTS: Our data showed partial immunoapresis was found in 63% MM patients. Partial immunoparesis was significantly related to elevated beta-2-microglobulin (B2M), decreased estimated glomerular filtration rate (eGFR) and progressive international staging system (ISS) stage (P<0.05). Especially, univariate Cox regression analysis showed partial immunoparesis was significantly correlated with early grade ≥3 infections (P=0.003). Moreover, multivariate Cox regression analysis showed partial immunoparesis was an independent significant prognostic factor for early grade ≥3 infections [odds ratio (OR) =3.048; 95% confidence interval (CI): 1.429-6.504; P=0.004]. Furthermore, partial immunoapresis could improve the infection risk model built by Dumontet et al. CONCLUSIONS: Our study showed that partial immunoparesis could predict early infections in patients with MM, which may be used to identify the high risk patients for infections and guide strategies for infection prevention.

CD8+GITR+ T cells may negatively regulate T cell overactivation in aplastic anemia.

Aplastic anemia (AA) is a T cell immune-mediated autoimmune disease. Overactivated CD8+ T cells play a leading role in the pathogenesis of AA, which may be due to disbalance in costimulatory and coinhibitory signals in T cells. In this study, we firstly investigated the expression of OX40, 4-1BB, GITR, ICOS, CTLA-4, LAG-3, and TIM-3 on CD8+ T cells from untreated patients with AA and healthy individuals (HIs) by flow cytometry. Moreover, we further analyzed the phenotype and functional characteristics of CD8+GITR+ T cells to more fully assess the T cell activation dysfunction in AA. We for the first time demonstrated significantly decreased percentage of CD8+GITR+ T cells in AA, and CD8+GITR+CTLA-4+ T cells were significantly higher in patients with AA compared with HIs. Conversely, the percentage of CD8+GITR+granzyme B+ and CD8+GITR+perforin+ T cells in AA patients was significantly reduced. Our preliminary data illustrate that the CD8+GITR+ T cell population might negatively regulate overactive T cell activation in AA.

Albumin improves stratification in the low IPI risk patients with diffuse large B-cell lymphoma.

Previous studies showed albumin at diagnosis could be used to predict outcome in patients with diffuse large B-cell lymphoma (DLBCL), but whether albumin could improve the international prognostic index (IPI) risk stratification remains unknown. Herein, we retrospectively analyzed 440 de novo DLBCL patients in this study. The cutoff value of albumin was 39.2 g/L. Patients with high serum albumin showed superior OS and PFS (p = 0.002 and p < 0.001, respectively). According to IPI, there were 163 patients (37.0%) in low-risk group, 107 (24.3%) in low-intermediate risk group, 114 (25.9%) in high-intermediate risk group and 56 (12.7%) in high-risk group. Further analysis showed high albumin could identify a subgroup of patients with extremely superior OS and PFS in low IPI risk patients (p = 0.022 and p = 0.034, respectively). Multivariate analysis revealed that high albumin was an independent prognostic factor for OS (relative ratio [RR] 0.122; 95% confidence interval [CI] 0.021-0.715, p = 0.020) and trend for PFS (RR 0.417; 95% CI 0.168-1.035, p = 0.059). In conclusion, our study suggests that albumin at diagnosis is a simple and effective prognostic factor in DLBCL patients, allowing the identification of a superior outcome subgroup in low-risk patients, which may help to guide treatment in clinical trial.

Consecutive Hypoalbuminemia Predicts Inferior Outcome in Patients With Diffuse Large B-Cell Lymphoma.

The prognostic value of albumin changes between diagnosis and end-of-treatment (EoT) in diffuse large B-cell lymphoma (DLBCL) remains unknown. We retrospectively analyzed 574 de novo DLBCL patients treated with R-CHOP from our and two other centers. All patients were divided into a training cohort (n = 278) and validation cohort (n = 296) depending on the source of the patients. Overall survival (OS) and progression-free survival (PFS) were analyzed by the method of Kaplan-Meier and Cox proportional hazard regression model. In the training cohort, 163 (58.6%) patients had low serum albumin at diagnosis, and 80 of them were present with consecutive hypoalbuminemia at EoT. Patients with consecutive hypoalbuminemia showed inferior OS and PFS (p = 0.010 and p = 0.079, respectively). Similar survival differences were also observed in the independent validation cohort (p = 0.006 and p = 0.030, respectively). Multivariable analysis revealed that consecutive hypoalbuminemia was an independent prognostic factor OS [relative risk (RR), 2.249; 95% confidence interval (CI), 1.441-3.509, p < 0.001] and PFS (RR, 2.001; 95% CI, 1.443-2.773, p < 0.001) in all DLBCL patients independent of IPI. In conclusion, consecutive hypoalbuminemia is a simple and effective adverse prognostic factor in patients with DLBCL, which reminds us to pay more attention to patients with low serum albumin at EoT during follow-up.

Publisher Correction: The international staging system improves the IPI risk stratification in patients with diffuse large B-cell lymphoma treated with R-CHOP.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.