The value of prognostic nutritional index in nasal-type, extranodal natural killer/T-cell lymphoma.

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive disorder with heterogeneous clinical characteristics and poor prognosis. The combined value of baseline serum albumin level and absolute peripheral lymphocyte count showed prognostic information in a variety of malignancies, but its evidence is limited in ENKTL. The purpose of this study is to evaluate the impact of prognostic nutritional index (PNI) in ENKTL, and to provide some nutritionally and immunologically relevant information for better risk stratification. We conducted a retrospective study in 533 patients newly diagnosed with ENKTL. The PNI was calculated as albumin (g/L) + 5 × lymphocyte count (109/L). The optimal cutoff values for serum albumin and lymphocyte count were 40.6 g/L and 1.18 × 109/L, respectively, and 47.3 for PNI. After a median follow-up of 70 months, the 5-year overall survival (OS) and progression-free survival (PFS) were 56.2% and 49.5%, respectively. Patients in low PNI group had more unfavorable clinical features, and tended to have worse 5-year OS and PFS compared with those in high PNI group. According PNI-associated prognostic score, patients were classified into different risk groups. Significant difference has been found in 5-year OS and PFS in different risk groups. When PNI and PNI-associated prognostic score were superimposed on the International Prognostic Index (IPI), prognostic index of natural killer lymphoma (PINK), or nomogram-revised risk index (NRI) categories, the PNI and PNI-associated prognostic score provided additional prognostic information. Therefore, PNI and PNI-associated prognostic score could be independent prognostic factors for ENKTL and may be useful for risk stratification and clinical decision-making.

How to Identify Patients at High Risk of Developing Nasal-Type, Extranodal Nature Killer/T-Cell Lymphoma-Associated Hemophagocytic Syndrome.

Nasal-type, extranodal nature killer (NK)/T-cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS) is a rare and life-threatening disease, requiring investigation of risk stratification. We conducted a retrospective study and proposed nomograms to predict NK/T-LAHS. The discriminative ability and calibration of the nomograms for prediction were tested using C statistics and calibration plots. We analyzed 533 patients with extranodal NK/T-cell lymphoma (ENKTL), out of which 71 were diagnosed with hemophagocytic syndrome (HPS), with a cumulative incidence of 13.3%. Significant difference for 2-year survival was found between patients with and without HPS (14.7% vs. 77.5%). Analyses showed that Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, B symptoms, and bone marrow (BM) invasion were significantly associated with NK/T-LAHS. We used these data as the basis to establish a nomogram of risk index for ENKTL (RINK). In 335 patients with available data for Epstein-Barr virus DNA (EBV-DNA), we found high viral copies (≥4,450 copies/ml) were correlated with NK/T-LAHS. When these data were added to RINK, we developed another nomogram that included EBV-DNA data (RINK-E). The nomograms displayed good accuracy in predicting NK/T-LAHS with a C-statistics of 0.919 for RINK and a C-statistics of 0.946 for RINK-E, respectively. The calibration chart also showed an excellent consistency between the predicted and observed probabilities. The proposed nomograms provided individualized risk estimate of HPS in patients with ENKTL.

A clinical study of 21 patients with hemophagocytic syndrome in 295 cases diagnosed with nasal type, extranodal nature killer/T cell lymphoma.

Nasal type, extranodal nature killer (NK)/T cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS) is a rare and fatal disorder with extremely poor prognosis. To investigate its clinical characteristics and risk factors, we retrospectively analyzed 295 patients with nasal type, extranodal nature killer/T cell lymphoma, of which 21 were diagnosed with hemophagocytic syndrome, with a cumulative incidence of 7.1%. The most frequently clinical characteristics were fever, lymphadenopathy, hepatosplenomegaly, pancytopenia, hyperferritinemia, liver dysfunction, hypertriglyceridemia, hypofibrinogenemia and evaluated lactate dehydrogenase (LDH) level. After a median follow-up of 27 months, the 2-year survival for the 295 patients was 74.6%. Significant difference for 2-year survival was found between patients with and without hemophagocytic syndrome (4.8% vs. 80.0%, P<0.001). After developing hemophagocytic syndrome, all patients survived no more than 3 months, with a median survival of 35 days. Risk factors for NK/T-LAHS were bone marrow (BM) involvement (P = 0.019; relative risk, 13.649; 95% confidence interval (CI): 1.538-121.103), hepatosplenomegaly (P = 0.003; relative risk, 9.616; 95%CI: 2.154-42.918), and elevated LDH level (>314U/L) (P = 0.038; relative risk, 6.293; 95%CI: 1.108-35.735). We conducted a risk model for all 295 patients based on the 3 adverse factors as follows: low risk (233 cases, 79.0%), no factor; intermediate risk (43 cases, 14.6%), one factor; high risk (19 cases, 6.4%), 2 or 3 factors. The probabilities for developing LAHS were 0.9% for low-, 14.0% for intermediate-, and 68.4% for high-risk group. Significant differences in the 3 risk groups were observed (P<0.001).

microRNA profile changes in development of NKT cells / 中国免疫学杂志

Objective:To explore the microRNA profile changes in the development of NKT cells.Methods: Differently developmental stage of NKT cells in mouse thymus were sorted by flow cytometry.Total RNA were extracted,reversely transcribed and pre-amplified.TaqMan low density microRNA assay and single real-time PCR were applied to detect the expression changes of microRNAs in the developmental process of NKT cells.Results: There were total 92 microRNAs whose expression changed significantly during the development and maturation of NKT cells.Among them,increasly expressed microRNAs were 71,including 36 microRNAs whose expression continuously increased;decreasly expressed microRNAs were 21,including 12 microRNAs whose expression continuously decreased.In addition,single real-time PCR analysis showed that the expression of Let-7f,miR-150,miR-24,miR-29 increased,while the expression of miR-223 and miR-155 decreased during the development and maturation of NKT cells.Conclusion: NKT development and maturation is accompanied by expression changes of large amount of microRNAs,indicating that specific microRNA regulates NKT development and function.

Changes of natural killer T cells levels in peripheral blood of children with asthma and clinical significance / 中华实用儿科临床杂志

Objective To study the changes of natural killer T cells (NKT cells) in peripheral blood and the ability of NKT cells to proliferate in response to alpha-galactosyl ceramide (α-Galcer) in children with asthma.Methods Fifty-two asthmatic children who were diagnosed by Pediatric Clinic of Renji Hospital Affiliated to Shanghai Jiaotong University Medical College from Feb.2009 to Mar.2012 were selected as asthmatic group (26 cases in intermittent group,14 cases in mild persistent group and 12 cases in moderate persistent group).Twenty healthy children were selected as healthy control group.Peripheral blood mononuclear cells were collected by way of density gradient centrifugation method from blood samples.The ratio of peripheral blood NKT and CD4 + NKT cells were assessed by immunolluorescence and flow cytometry assays.The relationships between the NKT cells number,CD4 + NKT cells and atopic indexes such as the total IgE,eosinophil cationic protein (ECP) and the severity of asthma were investigated.The levels of IFN-γ,IL-4,IL-10 in peripheral blood were measured by enzyme-linked immunosorbent assay after proliferate in response to α-Galcer.The data were analyzed by using statistics software.Results Compared with healthy control group,the ratio of peripheral blood NKT and CD4 + NKT cells in asthmatic patients were significantly decreased (all P ＜0.01) ; There were no significant differences in asthmatic patients among the subgroups in terms of severity (P ＞ 0.05).There was no significant correlation between the NKT cells,CD4 + NKT cells and atopic indexes such as the total IgE and ECP(all P ＞ 0.05).The level of IL-4 in serum secreted by NKT cells in asthmatic group was significantly higher than that of healthy control group (P ＜0.01) ;The level of IL-10 in serum secreted by NKT cells in asthmatic group was decreased significantly (P ＜0.01) ;There was no significant difference in IFN-γ secreted by NKT cells between the asthmatic group and healthy control group (P ＞ 0.05).Conclusion The pathogenesis of asthma may be related to the ratio and dysfunction of NKT cells and CD4 + NKT cells.