A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study.

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Survivin is a prognostic marker and therapeutic target for extranodal, nasal-type natural killer/T cell lymphoma.

BACKGROUND: The relationship between survivin and extranodal, nasal-type natural killer/T cell lymphoma (ENKTCL) was unclearly established yet. We here studied the potential prognostic roles of survivin and its implication as a target in ENKTCL therapy. METHODS: ENKTCL patients' peripheral blood were collected and tested by ELISA. ENKTCL cell lines were cultured with or without survivin inhibitor and tested by MTT and Flow cytometry. According to the gene expression profiles from the ArrayExpress Archive under E-TABM-702, survivin co-regulated cluster was established by Coupled Two-way Clustering Algorithm. RESULTS: Seventeen point six percent of total 17 ENKTCL patients were serum survivin-positive. These patients had poorer outcome than that of negative cases (P<0.01). Analysis of survivin co-regulation genes in ENKTCL revealed that survivin was significantly involved in pluripotency, drug resistance, cell cycle and proliferation, indicating that it should be one of key regulators in ENKTCL and might be a latent therapeutic target. Our results just showed that YM155, a survivin inhibitor, had strong anti-tumor effect on ENKTCL cell lines in a dose dependent manner. It increased sub-G1 phase population and reduced G1- and G2-M phase populations (P<0.05). In addition, combining YM155 with DDP induced a larger decrease in cell viability than either agent alone and had a higher inhibition rate than Bliss index, suggesting their synergistic inhibition. CONCLUSIONS: We concluded that survivin was a potential prognostic marker and a critical regulatory molecule in the pathological process of ENKTCL. It would be a promising target in drugs discovery for ENKTCL therapy.

Prognostic impact of absolute lymphocyte count/absolute monocyte count ratio and prognostic score in patients with nasal-type, extranodal natural killer/T-cell lymphoma.

Nasal-type, extranodal natural killer/T-cell lymphoma is a heterogeneous disorder with poor prognosis, requiring risk stratification in this population. The combined value of baseline absolute lymphocyte count and absolute monocyte count provided prognostic information in some malignancies. However, the evidence requires validation in extranodal natural killer/T-cell lymphoma. Aiming to investigate the prognostic significance of absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score for extranodal natural killer/T-cell lymphoma, a retrospective research was carried out. A total of 264 patients with newly diagnosed extranodal natural killer/T-cell lymphoma were analyzed in this study. The patients' absolute lymphocyte count and absolute monocyte count tested at initial diagnosis were collected. Receiver operating curve analysis showed that the optimal cut-off values for absolute lymphocyte count and absolute monocyte count were 1.0 × 109 and 0.5 × 109L-1, respectively, and for absolute lymphocyte count/absolute monocyte count ratio was 2.85. After a median follow-up of 27 months (range 1-87 months), the 3-year overall survival and progression-free survival was 75.4% and 67.6%, respectively. Patients with absolute lymphocyte count/absolute monocyte count ratio ≥ 2.85 had better 3-year overall survival and progression-free survival than those with absolute lymphocyte count/absolute monocyte count ratio <2.85 (p < 0.001). According to absolute lymphocyte count/absolute monocyte count prognostic score, significant difference has been noticed in 3-year overall survival and progression-free survival (p < 0.001) and high absolute lymphocyte count/absolute monocyte count prognostic score was associated with poorer survival. The International Prognostic Index and Korean Prognostic Index were used for prognosis and showed no significant difference. When adding absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score to the International Prognostic Index and Korean Prognostic Index model, additional prognostic information was found. These results suggest that absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score might be useful prognostic factors in extranodal natural killer/T-cell lymphoma.

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).

Serum B-cell activating factor predicts prognosis in nasal type, extranodal NK/T cell lymphoma.

B-cell activating factor (BAFF) plays important roles in a variety of lymphoid malignancies. Compared with healthy adults, patients with non-Hodgkin lymphoma had higher level of serum BAFF, and it corresponded with disease severity, response for therapy and clinical outcome. Latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) which is a known agent of nasal, extranodal NK/T cell lymphoma (ENKTCL) can switch the BAFF activating promoter leading to higher expression of BAFF in EBV-related tumor cells. However, the relationship between BAFF and ENKTCL has not been reported. Here we proposed a hypothesis that BAFF might play a regulatory role in ENKTCL development and maintenance. Our results showed that serum BAFF in ENKTCL patients was significantly higher than that in control group and negatively correlated with patients' survival. It may be a valuable prognostic factor and deserved further study.