Zhong Jun Xia

First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/T-cell lymphoma

Extranodal natural killer/T‐cell lymphoma, nasal type (ENKTL) is a distinct subtype of non‐Hodgkin lymphoma in which the upper aerodigestive tract is the most commonly involved site. To date, optimal treatment strategies and prognosis for patients with ENKTL have not been fully defined.

Beclin 1 expression: A predictor of prognosis in patients with extranodal natural killer T-cell lymphoma, nasal type

Beclin 1 plays an important role in autophagy, differentiation, antiapoptosis and the development and progression of cancer. The function and expression of Beclin 1 in natural killer T-cell lymphoma is largely unexplored. The study aimed to investigate Beclin 1 expression and its relationship with prognosis in extranodal natural killer T-cell lymphoma, nasal-type (ENKL). Beclin 1 protein expression in 65 tumor specimens from patients newly diagnosed with ENKL was examined by immunohistochemistry (IHC). The clinical significance of Beclin 1 in ENKL was statistically analyzed. Immunopositivity for Beclin 1 was found in 56 (86.2%) of the 65 samples. Low Beclin 1 expression was significantly associated with advanced Ann Arbor stage, intermediate to high IPI risk and elevated LDH level. Low Beclin 1 expression was associated with worse overall survival (OS; p = 0.001) and progression-free survival (PFS; p = 0.017). In multivariate analysis, Beclin 1 expression, advanced Ann Arbor stage and B symptoms were found to be independent prognostic factors of OS and PFS. Consequently, a new clinico-pathological prognostic model was proposed. The model could discriminate different survival outcomes between low risk and high risk groups based on OS and PFS (p < 0.0001, respectively). Beclin 1 expression is predictive of prognosis in ENKL. The new clinico-pathological prognostic model may be help identify patients with different clinical outcomes.

Serum levels of soluble programmed death ligand 1 predict treatment response and progression free survival in multiple myeloma

Immune checkpoint signaling plays an important role in immunosuppression in multiple myeloma (MM). Blood levels of soluble programmed death-ligand 1 (sPD-L1), a checkpoint-relevant protein, might predict treatment response and survival outcomes in MM patients. We used an enzyme-linked immunosorbent assay to measure serum sPD-L1 levels in 81 newly diagnosed MM patients. We found that myeloma patients had higher sPD-L1 concentrations than healthy controls. The best sPD-L1 cutoff value for predicting disease progression risk was 2.783 ng/mL. The overall response rate to treatment was higher in low sPD-L1 patients than in high sPD-L1 patients. The 3-year progression free survival (PFS) and overall survival (OS) rates for all patients were 16% and 64%, respectively. Multivariate survival analysis including Eastern Cooperative Oncology Group performance status score, treatment response, and sPD-L1 level showed that a less than partial treatment response (PR) and higher sPD-L1 levels (>2.783 ng/ml) were independent prognostic factors for shorter PFS; neither factor was predictive of OS. The serum sPD-L1 level is a valuable biomarker for predicting treatment response and an independent prognostic factor for PFS. PD-1/PD-L1 blockade may be a promising novel immune-based therapeutic strategy in MM.

Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis.

Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma (NPC); however, it is not known whether locoregional radiotherapy targeting the primary tumor and regional lymph nodes affects the survival of patients with metastatic NPC. Therefore, we aimed to retrospectively evaluate the benefits of locoregional radiotherapy. A total of 408 patients with metastatic NPC were included in this study. The mortality risks of the patients undergoing supportive treatment and those undergoing chemotherapy were compared with that of patients undergoing locoregional radiotherapy delivered alone or in combination with chemotherapy. Univariate and multivariate analyses were conducted. The contributions of independent factors were assessed after adjustment for covariates with significant prognostic associations (P < 0.05). Both locoregional radiotherapy and systemic chemotherapy were identified as significant independent prognostic factors of overall survival (OS). The mortality risk was similar in the group undergoing locoregional radiotherapy alone and the group undergoing systemic chemotherapy alone [multi-adjusted hazard ratio (HR) = 0.9, P = 0.529]; this risk was 60% lower than that of the group undergoing supportive treatment (HR = 0.4, P = 0.004) and 130% higher than that of the group undergoing both systemic chemotherapy and locoregional radiotherapy (HR = 2.3, P < 0.001). In conclusion, locoregional radiotherapy, particularly when combined with systemic chemotherapy, is associated with improved survival of patients with metastatic NPC.

Primary gastric non-Hodgkin's lymphoma in Chinese patients: clinical characteristics and prognostic factors

BackgroundOptimal management and outcome of primary gastric lymphoma (PGL) have not been well defined in the rituximab era. This study aimed to analyze the clinical characteristics, prognostic factors, and roles of different treatment modalities in Chinese patients with PGL.MethodsThe clinicopathological features of 83 Chinese patients with PGL were retrospectively reviewed. Staging was performed according to the Lugano staging system for gastrointestinal non-Hodgkins lymphoma.ResultsThe predominant pathologic subtype among Chinese patients with PGL in our study was diffuse large B cell lymphoma (DLBCL), followed by mucosa-associated lymphoid tissue (MALT) lymphoma. Among the 57 patients with gastric DLBCL, 20 patients (35.1%) were classified as the germinal center B cell-like (GCB) subtype and 37 patients (64.9%) as the non-GCB subtype. The 83 patients had a five-year overall survival (OS) and event-free survival (EFS) of 52% and 59%, respectively. Cox regression analysis showed that stage-modified international prognostic index (IPI) and performance status (PS) were independent predictors of survival. In the 67 B-cell lymphoma patients who received chemotherapy, 36 patients treated with rituximab (at least 3 cycles) had a mean OS of 72 months (95% CI 62-81) versus 62 months (95% CI 47-76) for patients without rituximab treatment (P = 0.021).ConclusionThe proportion of Chinese gastric DLBCL cases with non-GCB subtype was higher than the GCB subtype. Stage-modified IPI and PS were effective prognostic factors in Chinese patients with PGL. Our data suggested that primary gastric B-cell lymphoma might have an improved outcome with rituximab in addition to chemotherapy. More studies are necessary, preferentially large prospective randomized clinical trials to obtain more information on the impact of the rituximab in the primary gastric B-cell lymphoma.

The glasgow prognostic score (gps) as a novel and significant predictor of extranodal natural killer/t-cell lymphoma, nasal type

The Glasgow Prognostic Score (GPS), an inflammation‐based prognostic score including C‐reactive protein and albumin, shows significant prognostic value in several types of solid tumors. The prognostic value of GPS in lymphoma remains unclear. We performed this study to evaluate the prognostic significance of GPS in extranodal natural killer (NK)/T‐cell lymphoma (ENKL). We retrospectively analyzed 164 patients with newly diagnosed ENKL. The prognostic value of GPS was evaluated and compared with that of International Prognostic Index (IPI), Prognostic Index for Peripheral T‐cell lymphoma unspecified (PIT), and Korean Prognostic Index (KPI). Patients with higher GPS tended to have more adverse clinical characteristics, lower rates of complete remission (P < 0.001), inferior progression‐free survival (PFS, P < 0.001), and inferior overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS, age > 60 years, and elevated LDH were independent adverse predictors of OS. GPS was found superior to IPI, PIT, and KPI in discriminating patients with different outcomes in low‐risk groups (all P < 0.05). GPS is an independent predictor of survival outcomes in ENKL. Inflammatory response might play an important role in the progression of ENKL and survival of patients with ENKL. Am. J. Hematol. 88:394–399, 2013.

Prognostic Value of Interim and Posttherapy 18F-FDG PET/CT in Patients with Mature T-Cell and Natural Killer Cell Lymphomas

The prognostic value of interim PET or PET/CT performed after 1–4 cycles of chemotherapy has been widely confirmed in Hodgkin lymphoma and diffuse large B-cell lymphoma but remains unknown in T-cell and natural killer (T/NK) cell lymphomas. Therefore, our aim was to investigate the prognostic value of interim and posttherapy PET/CT in T/NK-cell lymphomas. Methods: A retrospective analysis was conducted on data from 88 patients with newly diagnosed T/NK-cell lymphoma who underwent interim (after 1–4 cycles of chemotherapy, n = 62) or posttherapy PET/CT (after the completion of first-line therapy, n = 47). Interim and posttherapy PET/CT status (positive vs. negative) was visually interpreted according to criteria of the International Harmonization Project, and PET/CT status was assessed for its ability to predict progression-free survival (PFS) and overall survival (OS). Results: Interim PET/CT results were negative in 17 of 62 (27.4%) cases, and posttherapy PET/CT results were negative in 29 of 47 (61.7%) cases. The 2-y PFS and OS rates were 71.9% and 80.2%, respectively, in patients with negative results at interim PET/CT versus 20.5% and 46.9%, respectively, in patients with positive results (P < 0.001 and P = 0.022, respectively). The 2-y PFS and OS rates were 57.8% and 78.0%, respectively, in patients with negative results on posttherapy PET/CT versus 0% and 20.4%, respectively, in patients with positive results (P < 0.001 and P = 0.003, respectively). Bivariate analysis showed that interim PET/CT status and posttherapy PET/CT status remain independent predictors of PFS and OS after controlling for the score on the Prognostic Index for Peripheral T-Cell Lymphoma, Unspecified. Conclusion: Both interim PET/CT status and posttherapy PET/CT status are independent predictors of PFS and OS in T/NK-cell lymphomas.

Serum C-Reactive Protein (CRP) as a Simple and Independent Prognostic Factor in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

Background C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). Methods We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Results Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Conclusions Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI.

Expression of BAFF and BAFF-R in Follicular Lymphoma: Correlation with Clinicopathologic Characteristics and Survival Outcomes

Background B-cell activation factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the viability and proliferation of malignant lymphoma cells. Limited information exists regarding expression profiles and the prognostic role of BAFF and BAFF-R in follicular lymphoma (FL). We sought to determine the expression profiles of BAFF and BAFF-R in FL and to evaluate the correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and outcome of FL. Correlation between expression levels of BAFF detected by immunohistochemical (IHC) and serum levels of BAFF was also evaluated. Methods Paraffin-embedded specimens from 115 patients were immunohistochemically examined for BAFF and BAFF-R expression. Expression levels were dichotomized into low versus high categories based on immunostaining intensity. The correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and patient outcome was assessed. Serum levels of BAFF in 35 of the 115 patients with IHC data were measured by Enzyme-linked Immunosorbent assay (ELISA). Results BAFF and BAFF-R were expressed in 88.7% (102/115) and 87.8% (101/115) of the cases, respectively. BAFF expression was significantly correlated with only one clinicopathologic feature: Ann Arbor stage. No significant correlation was found between expression levels of BAFF detected by IHC and serum levels of BAFF detected by ELISA. High expression of BAFF-R, but not BAFF, was significantly correlated with inferior progression-free survival (PFS; P = 0.013) and overall survival (OS; P = 0.03). High expression of BAFF-R, bulky disease, and elevated lactate dehydrogenase were correlated with inferior PFS and OS in multivariate analysis. A prognostic scoring system incorporating these 3 risk factors identified 3 distinct prognostic groups with 5-year PFS of 59.4%, 41.9%, and 10.7% and OS of 91.3%, 79.7%, and 45.8%, respectively. Conclusions Most patients with FL variably express BAFF and BAFF-R. High expression of BAFF-R, but not BAFF, may be an independent risk factor for PFS and OS in FL.

Post-treatment plasma EBV-DNA positivity predicts early relapse and poor prognosis for patients with extranodal NK/T cell lymphoma in the era of asparaginase

Circulating Epstein-Barr virus (EBV) DNA is a biomarker of EBV-associated malignancies. Its prognostic value in early stage NK/T-cell lymphoma (NKTCL) in the era of asparaginase was investigated. 68 patients were treated with a median of 4 cycles of asparaginase-based chemotherapy followed by a median of 54.6Gy (range 50–60Gy) radiation. The amount of EBV-DNA was prospectively measured in both pretreatment and post-treatment plasma samples by real-time quantitative PCR. At the end of treatment, complete response (CR) rate was 79.4%, and overall response rate (ORR) was 88.2%. Patients with negative pretreatment EBV-DNA had a higher CR rate (96.0% vs. 69.8%, p = 0.023). The 3-year progression-free survival (PFS) rate and overall survival (OS) rate was 71% and 83%, respectively. In multivariate survival analysis, post-treatment EBV-DNA positivity and treatment response (non-CR) were prognostic factors for both worse PFS and OS (p < 0.05). Local tumor invasion was also a prognostic factor for worse OS (p = 0.010). In patients with CR, post-treatment EBV-DNA positivity correlated with inferior PFS and OS (both p < 0.0001). In patients with positive pretreatment EBV-DNA, negative post-treatment EBV-DNA correlated with better PFS and OS (both p < 0.0001). These findings indicate that post-treatment EBV-DNA positivity can predict early relapse and poor prognosis for patients with early stage NKTCL in the era of asparaginase, and may be used as an indicator of minimal residual disease.