BACKGROUND: 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. METHODS: This prospective study was conducted to evaluate the efficacy and safety profiles of first‐line combined gemcitabine, oxaliplatin, and L‐asparaginase (GELOX) followed by involved‐field radiation therapy for patients with stage IE/IIE ENKTL. The primary endpoints were the complete response rate, the objective response rate, and toxicities. Secondary endpoints were overall survival and progression‐free survival. RESULTS: Twenty‐seven patients with newly diagnosed ENKTL were enrolled and completed the entire course of treatment. At the end of treatment, the overall response rate was 96.3%, including 20 patients (74.1%) who attained a complete response and 6 patients (22.2%) who attained a partial response. No patients developed disease progression during therapy. Grade 1 and 2 toxicities were frequent during GELOX, but grade 3 and 4 toxicities were few, and no treatment‐related deaths occurred. At a median follow‐up of 27.37 months, 7 patients (25.9%) experienced disease progression, and 4 of those patients died of disease. The rates of 2‐year overall and progression‐free survival were both 86%, and patients who attained a complete response at the end of treatment had significantly longer progression‐free survival (P = .012) and overall survival (P = .021) than patients who did not attain a complete response. CONCLUSIONS: The current results indicated that GELOX followed by involved‐field radiation therapy can be an effective and feasible treatment strategy for patients with stage IE/IIE ENKTL of the upper aerodigestive tract. These results will require further investigation in larger prospective trials. Cancer 2013. © 2012 American Cancer Society.

BackgroundRecent research has shown a correlation between immune microenvironment and lymphoma biology. This study aims to investigate the prognostic significance of the immunologically relevant lymphocyte-to-monocyte ratio (LMR), in diffuse large B-cell lymphoma (DLBCL) in the rituximab era.Methodology/Principal FindingsWe analyzed retrospective data from 438 newly diagnosed DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. We randomly selected 200 patients (training set) to generate a cutoff value for LMR by receiver operating characteristic (ROC) curve analysis. LMR was then analyzed in a testing set (n = 238) and in all patients (n = 438) for validation. The LMR cutoff value for survival analysis determined by ROC curve in the training set was 2.6. Patients with low LMR tended to have more adverse clinical characteristics. Low LMR at diagnosis was associated with worse survival in DLBCL, and could also identify high-risk patients in the low-risk IPI category. Multivariate analysis identified LMR as an independent prognostic factor of survival in the testing set and in all patients.Conclusions/SignificanceBaseline LMR, a surrogate biomarker of the immune microenvironment, is an effective prognostic factor in DLBCL patients treated with R-CHOP therapy. Future prospective studies are required to confirm our findings.

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.

BackgroundExtranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL.MethodsRetrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis.ResultsThe AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category.ConclusionThe baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL.

BackgroundC-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).MethodsWe 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.ResultsPatients 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.ConclusionsOur 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.

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 5 62) or posttherapy PET/CT (after the completion of first-line therapy, n 5 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 5 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 5 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.

BackgroundHIV-negative, CD20-negative de novo diffuse large B-cell lymphoma (DLBCL) patients has rarely been reported. To elucidate the nature of this entity, we retrospectively reviewed the data of 1,456 consecutive de novo DLBCL patients who were treated at Sun Yat-Sen University Cancer Center between January 1999 and March 2011.MethodsThe pathologic characteristics of CD20-negative patients, clinical features, response to initial treatment, and outcomes of 28 patients with available clinical data (n = 21) were reviewed. Then, a matched case-control (1:3) analysis was performed to compare patients with CD20-negative and -positive DLBCL.ResultsThe median age of the 28 CD20-negative DLBCL patients was 48 years, with a male-female ratio of 20:8. Seventeen of 22 (77.3%) CD20-negative DLBCL cases were of the non-germinal centre B-cell (non-GCB) subtype. High Ki67 expression (≥80%), an index of cell proliferation, was demonstrated in 17 of 24 (70.8%) cases. Extranodal involvement (≥ 1 site) was observed in 76.2% of the patients. Following initial therapy, 9 of 21 (42.9%) cases achieved complete remission, 4 (19%) achieved partial remission, 1 (4.8%) had stable disease, and 7 (33.3%) had disease progression. The median overall survival was 23 months. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 30.5% and 35%, respectively. A matched case-control analysis showed that patients with CD20-negative and -positive DLBCL did not exhibit a statistically significant difference with respect to the main clinical characteristics (except extranodal involvement), whereas the patients with CD20-positive DLBCL had a better survival outcome with 3-year PFS (P = 0.008) and OS (P = 0.008) rates of 52% and 74.1%, respectively.ConclusionsThis study suggests that HIV-negative, CD20-negative de novo DLBCL patients have a higher proportion of non-GCB subtype, a higher proliferation index, more frequent extranodal involvement, a poorer response, and a poorer prognosis to conventional treatment compared to patients with CD20-positive DLBCL. Further studies are warranted to investigate new target and optimal therapy of CD20-negative de novo DLBCL.

BackgroundEpstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) in the elderly has rarely been reported. This study aimed to explore the clinical characteristics and prognosis of this entity.MethodsIn situ hybridization (ISH) analysis of Epstein-Barr virus (EBV) and immunohistochemistry was performed in 230 tumor specimens from consecutive de novo DLBCL patients over 50 years old. A matched-case control analysis (1:3) was utilized to compare EBV-positive and EBV-negative DLBCL in the elderly.ResultsA total of 16 patients (7.0%) were diagnosed with EBV-positive DLBCL. Of these 16 cases, the median age was 62 years, with a male to female ratio of 11:5. Elderly EBV-positive DLBCL patients had a higher incidence of non-germinal center B-cell (non-GCB) subtypes (87.5%) and high Ki67 (75%) and CD30 expression (93.8%). For EBV-positive patients undergoing initial chemotherapy, 7 of 16 (43.8%) had complete remission, 2 (12.5%) had partial remission, 2 (12.5%) had stable disease, and 5 (31.3%) had progressive disease. The median overall survival was 9 months for the EBV-positive patients. A matched-case control analysis suggested that EBV-positive patients had inferior survival outcomes compared with EBV-negative patients (3-year progression-free survival [PFS]: 25% vs. 76.7%, respectively; 3-year overall survival [OS]: 25% vs. 77.4%, respectively; P<0.001).ConclusionEBV-positive DLBCL of the elderly is associated with an inferior clinical course and inferior survival outcomes. The role of EBV in this disease and the optimal management of this subgroup warrants further investigation.