Correlation of serum metabolites and clinical features in patients with peripheral T-cell lymphoma / 陆军军医大学学报

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

Clinicopathological Study of Two Cases of Extranodal NK/T-cell Lymphoma with B-Lymphocytosis / 现代检验医学杂志

Objective To investigate the clinicopathological characteristics of extranodal NK/T cell lymphoma(ENKTL)with B-lymphocytosis.Methods Two cases of ENKTL with B-lymphocytosis diagnosed in Shaanxi Provincial People's Hospital from June to September 2023 were collected.HE staining,immunohistochemistry,and in situ hybridisation Epstein-barr virus encoded small RNA(EBER)testing was used to observe the histological features,immunophenotypes,and results of the in situ hybridisation EBER testing.A review of the relevant literature was conducted.Results In two cases of elderly male patients,whose lesion sites were on both the right side of the nasal cavity,histological characteristics of the tumor cells were diffuse distribution.The cells were of different sizes,mainly medium and large cells,with irregular nuclei,stained or transparent cytoplasm,oval nuclei,granular chromatin and inconspicuous nucleoli.Nuclear schizophrenia was more common and coagulative necrosis and apoptosis were evident.Foci of small lymphocyte aggregates were seen in the background and lymphoid follicles were distributed in a scattered manner.Immunohistochemical CD2,CD3,CD56,TIA-1 and granzyme B(GrB)were positive.CD20,CD79a and PAX-5 were focal positive.CD21,CD23 and CD35 had residual FDC network,and CD5 was negative.Ki-67 proliferation index was approximately 30%.EBER tumor cells detected by in situ hybridisation were positive.Pathological diagnosis showed ENKTL with B-lymphocytosis.Conclusion NKTL with B-lymphocytosis was rare,especially when B-lymphocyte hyperplasia formed lymphoid follicles.Lack of experience can easily cause diagnostic difficulties,and comprehensive analysis and diagnosis should be combined with the clinical manifestations,histological morphology and immunophenotype.

Prognostic value of 18F-FDG PET/CT combined with clinical staging/scoring system in nasal extranodal natural killer/T-cell lymphoma / 中华核医学与分子影像杂志

Objective:To compare and choose the best method for measuring metabolic tumor volume (MTV) of nasal extranodal natural killer/T-cell lymphoma (ENKTL), evaluate the prognostic value of 18F-FDG PET/CT metabolic parameters and clinical staging/scoring systems for patients with nasal ENKTL, and explore the added value of the two combinations for prognostic prediction. Methods:From January 2016 to September 2022, 44 patients (26 males, 18 females; age (47.5±13.6) years) pathologically diagnosed with nasal ENKTL who underwent 18F-FDG PET/CT imaging before treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively collected. SUV 2.5, SUV 4.0 and 41%SUV max were used as thresholds to measure MTV and total lesion glycolysis (TLG), and the consistency was analyzed by Bland-Altman analysis. The ROC curve analysis was used to compare the prognostic efficiency of different methods and determine the best method. The prognostic values of different clinical factors and clinical staging/scoring systems between groups were evaluated by corrected χ2 test. The independent factors were screened by Cox-regression model, and the combined diagnosis model was constructed by logistic regression. Results:Of 44 patients, 6(13.6%) were dead, with the overall survival (OS) of 32.05(11.77, 64.43) months, and the 2-year and 5-year OS rates of 86.6% and 82.5%, respectively. The mortality of different groups in age (≥60 and <60 years), prognostic index of natural killer cell lymphoma (PINK) score (low- and high-risk), and international prognostic index (IPI) score (low- and high-risk) were significantly different ( χ2 values: 5.02, 4.12, 3.88, all P<0.05). The consistency of MTV measured by different thresholds was good. Among them, the MTV measured by threshold of SUV 2.5 had the highest predictive efficiency with the AUC of 0.737. Multivariate analysis showed that MTV (hazard ratio ( HR)=10.488, 95% CI: 1.864-59.026, P=0.008) was the independent influencing factor of OS. By removing other factors, minimization model was obtained, including MTV and PINK score ( P values: 0.006, 0.048). The prediction model of MTV combined with PINK score improved prognostic efficacy with the AUCs of MTV, PINK score and the combination model of 0.781, 0.741 and 0.912, respectively. Conclusions:MTV measured by threshold of SUV 2.5 has better prognostic predictive value. MTV is the independent prognostic factor for OS in nasal ENKTL patients. MTV combined with PINK score has better prognostic value.

Clinical analysis of seven cases of hemophagocytic lymphohistiocytosis secondary to cutaneous T-cell lymphoma / 中华皮肤科杂志

Objective:To investigate clinical and laboratory characteristics of secondary hemophagocytic lymphohistiocytosis (sHLH) associated with secondary cutaneous T-cell lymphoma (CTCL) .Methods:CTCL patients with clinically suspected sHLH were collected from Department of Hematology, Wuhan No.1 Hospital from January 2016 to October 2021, and were evaluated according to the HLH-2004 diagnostic criteria and HScore.Results:Seven CTCL patients were confirmedly diagnosed with sHLH, including 2 with primary cutaneous γδT-cell lymphoma (PC-GDTCL) , 3 with cutaneous extranodal natural killer/T-cell lymphoma (C-ENKTCL) , and 2 with primary cutaneous anaplastic large cell lymphoma (PC-ALCL) . All the 7 patients received chemotherapy, but 6 died finally, and the median overall survival duration was 26.5 days (range: 14 - 60 days) after the confirmed diagnosis of CTCL complicated by sHLH. HLH-related gene mutations, which were located in the PRF1 and LYST genes, were identified in 2 patients; lymphoma-related gene mutations were identified in the KRAS and KMT2D genes in 1 PC-GDTCL patient,and in the JAK3 and SAMHD1 genes in another PC-GDTCL patient.Conclusions:CTCL complicated by sHLH usually progresses rapidly, so early diagnosis and treatment are needed. Bone marrow biopsy and mutation screening of lymphoma- and HLH-related genes at initial diagnosis and during disease progression may facilitate early diagnosis.

Progress of immunotherapy for NK/T cell leukemia/lymphoma / 白血病·淋巴瘤

NK/T cell leukemia/lymphoma is a type of malignancy originating from T cells or natural killer cells with low incidence and poor clinical prognosis. There is still no effective treatment strategy. In recent years, targeted therapy has made great progress in the treatment of hematological malignancies, including monoclonal antibody and chimeric antigen receptor T cells (CAR-T), among which CD30, CD7, CD5, CD52, CCR4 and other target antigens are effective in the treatment of NK/T cell leukemia/lymphoma, but its widespread application still faces a great challenge. This article reviews the progress of immunotherapy for NK/T cell leukemia/lymphoma.

Progress of immune checkpoint inhibitors in extranodal NK/T cell lymphoma / 白血病·淋巴瘤

Extranodal NK/T cell lymphoma (ENKTCL) is a group of highly aggressive non-Hodgkin lymphoma associated with epstein-barr virus infection. Asparaginase-based chemoradiotherapy regimens are not effective in advanced patients. In recent years, anti-programmed-death receptor 1 (PD-1)/programmed-death receptor ligand 1 (PD-L1) immunotherapy has developed rapidly, which can effectively improve the prognosis of ENKTCL patients. But some patients with ENKTCL still have low response rate. This article reviews the mechanisms of resistance to anti-PD1/PD-L1 therapy and other immune targets in ENKTCL recently to change the traditional treatment mode of ENKTCL through the combination of different targeted drugs.

Efficacy and safety of SIMPLE regimen in treatment of extranodal NK/T-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of SIMPLE regimen in the treatment of extranodal NK/T-cell lymphoma (ENKTCL).Methods:The clinical data of 11 patients with ENKTCL who were admitted to the University of Hong Kong-Shenzhen Hospital from January 2012 to January 2022 were retrospectively analyzed. The patients received 4-6 courses of SIMPLE (cisplatin, gemcitabine, ifosfamide, etoposide, dexamethasone, and pegasparaginase) regimen chemotherapy, and stage Ⅰ and Ⅱ patients who also received local radiotherapy after 2 or 3 courses of chemotherapy. Patients were evaluated for mid-treatment and end-of-treatment outcomes, and the adverse effects of patients were evaluated in each treatment cycle. The Kaplan-Meier method was used to analyze the progression-free survival (PFS) and overall survival (OS) of the 11 patients.Results:All 11 patients were nasal type, with the median age of 41 years old (26-67 years old), including 5 males and 6 females, 3 relapsed cases and 8 newly treated cases. Of the 10 patients evaluated for efficacy, 9 achieved complete remission and 1 achieved at least partial remission (efficacy was assessed based on follow-up). All 11 patients were followed up for a median time of 50 months (15-72 months) and 2 relapsed patients died due to disease progression. The expected 5-year PFS rate and OS rate of 11 patients were both 90.0%, and the expected 5-year OS rate was 100.0% and 66.6% in newly treated and relapsed patients, respectively. Common adverse effects were hematologic adverse reactions, infections, gastrointestinal symptoms, elevated transaminases, and hypofibrinogenemia, all of which were curable. There is no treatment-related death.Conclusions:The SIMPLE regimen for the treatment of ENKTCL has a high remission rate, the patients have long survival time, and the regimen is moderately well tolerated.

Extranodal NK/T cell lymphoma, nasal type involving the larynx and digestive tract: a case report and literature review / 临床耳鼻咽喉头颈外科杂志

Extranodal NK/T cell lymphoma, nasal type（ENKTL） is a highly aggressive malignant tumor derived from NK cells. This article reports a case of ENKTL invading the larynx and digestive tract. The clinical clinical manifestations include hoarseness and intranasal masses.

Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study / 中华血液学杂志

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

Diagnostic and prognostic value of bone marrow biopsy in patients with extranodal NK/T-cell lymphoma based on PET-CT staging / 中华放射肿瘤学杂志

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

Influence of Pre-treatment Lymphocyte/Monocyte Ratio and Neutrophil/Lymphocyte Ratio on the Prognosis of Patients with Extranodal NK/T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL).@*METHODS@#The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS.@*RESULTS@#The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high β2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL.@*CONCLUSION@#Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.

Regulation of Baicalin on Growth of Extranodal NK/T Cell Lymphoma Cells through FOXO3/CCL22 Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of baicalin on the growth of extranodal NK/T cell lymphoma (ENKTCL) cells and its related mechanism.@*METHODS@#Normal NK cells and human ENKTCL cells lines SNK-6 and YTS were cultured, then SNK-6 and YTS cells were treated with 5, 10, 20 μmol/L baicalin and set control. Cell proliferation and apoptosis was detected by Edu method and FCM method, respectively, and expressions of BCL-2, Bax, FOXO3 and CCL22 proteins were detected by Western blot. Interference plasmids were designed and synthesized. FOXO3 siRNA interference plasmids and CCL22 pcDNA overexpression plasmids were transfected with PEI transfection reagent. Furthermore, animal models were established for validation.@*RESULTS@#In control group and 5, 10, 20 μmol/L baicalin group, the proliferation rate of SNK-6 cells was (56.17±2.96)%, (51.92±4.63)%, (36.42±1.58)%, and (14.60±2.81)%, respectively, while that of YTS cells was (58.85±2.98)%, (51.38±1.32)%, (34.75±1.09)%, and (15.45±1.10)%, respectively. In control group and 5, 10, 20 μmol/L baicalin group, the apoptosis rate of SNK-6 cells was (5.93±0.74)%, (11.78±0.34)%, (28.46±0.44)%, and (32.40±0.37)%, respectively, while that of YTS cells was (7.93±0.69)%, (16.29±1.35)%, (33.91±1.56)%, and (36.27±1.06)%, respectively. Compared with control group, the expression of BCL-2 protein both in SNK-6 and YTS cells decreased significantly (P<0.001), and the expression of Bax protein increased in SNK-6 cells only when the concentration of baicalin was 20 μmol/L (P<0.001), while that in YTS cells increased in all three concentrations(5, 10, 20 μmol/L) of baicalin (P<0.001). The expression of FOXO3 protein decreased while CCL22 protein increased in ENKTCL cell lines compared with human NK cells (P<0.001), but the expression of FOXO3 protein increased (P<0.01) and CCL22 protein decreased after baicalin treatment (P<0.001). Animal experiments showed that baicalin treatment could inhibit tumor growth. The expression of CCL22 protein in ENKTCL tissue of nude mice treated with baicalin decreased compared with control group (P<0.01), while the FOXO3 protein increased (P<0.05). In addition, FOXO3 silencing resulted in the decrease of FOXO3 protein expression and increase of CCL22 protein expression (P<0.01, P<0.001).@*CONCLUSION@#Baicalin can inhibit proliferation and promote apoptosis of ENKTCL cell lines SNK-6 and YTS, up-regulate the expression of Bax protein, down-regulate the expression of BCL-2 protein, and down-regulate the expression of CCL22 protein mediated by FOXO3. Animal experiment shown that the baicalin can inhibit tumor growth. Baicalin can inhibit the growth and induce apoptosis of ENKTCL cells through FOXO3/CCL22 signaling pathway.

Safety and efficacy of upfront autologous transplantation as a consolidation therapy for progressive nasal type extranodal NK/T-cell lymphoma / 中华器官移植杂志

Objective:To evaluate the efficacy and safety of upfront autologous hematopoietic stem cell transplantation(auto-HSCT)as a consolidation therapy of progressive nasal type extranodal NK/T-cell lymphoma, (ENKL).Methods:From January 2012 to June 2021, clinical data were retrospectively reviewed for 28 patients with advanced-stage ENKL on chemotherapy of asparaginase-containing regimen followed by upfront auto-HSCT as a consolidation therapy.The median age at transplantation was 34.5(14-61)years.There were 19 males and 9 females.Clinical types were nasal(n=22)and non-nasal(n=6). Clinical stages were Ann Arbor III(n=15)and IV(n=13). Clinical risks were intermediate(n=8)and high(n=20)according to the Prognostic Index for Natural-Killer cell lymphoma-Epstein-Barr virus(PINK-E).Results:Hematopoietic reconstruction was performed.Median time of neutrophil engraftment was 10(8-17)days and 13(10-22)days for platelet.Median follow-up time was 59.5 months and 5-year OS/PFS 70.0%(95% CI: 50.60%-89.40%)and 59.1%(95% CI: 39.11%-79.10%). And 5-year cumulative recurrence and non-recurrence mortality rates were 35.42%(95% CI: 19.11%-59.39%)and 4.2%(95% CI: 2.16%-29.87%). Conclusions:Asparaginase-based chemotherapy followed by auto-HSCT is both safe and efficacious for progressive ENKTL.

Value of pretreatment albumin in prognostic assessment of extranodal nasal type NK/T cell lymphoma / 肿瘤研究与临床

Objective:To explore the prognostic value of pretreatment albumin in extranodal nasal type NK/T cell lymphoma (ENKTL).Methods:The clinical data of 184 ENKTL patients in Shanxi Province Cancer Hospital from January 2002 to December 2018 were retrospectively analyzed. The Contal-O'Quigley change point method was used to determine the optimal cut-off value of albumin for predicting the prognosis of patients. The propensity score matching (PSM) was used to minimize selection biases. The Kaplan-Meier method was used for survival analysis, and Cox proportional hazards model was used to determine the factors affecting survival. The time-dependent receiver operating characteristic curve, Akaike information criterion and integrated Brier score were used to evaluate the efficacy of international prognostic index (IPI), Korean prognostic index (KPI) and prognostic index of NK cell lymphoma (PINK) models incorporating albumin for predicting the prognosis of patients.Results:The optimal cut-off value of pretreatment albumin for predicting the prognosis of ENKTL patients was 37.5 g/L. The 3-year and 5-year overall survival (OS) rates in >37.5 g/L group (126 cases) were 66.2% and 60.3%, and the progression-free survival (PFS) rates were 58.8% and 49.6%; the 3-year and 5-year OS rates in ≤37.5 g/L group (58 cases) were 35.0% and 32.4%, and the PFS rates were 32.5% and 30.0%. The OS and PFS in > 37.5 g/L group were better than those in ≤37.5 g/L group (both P<0.001). After PSM, the OS and PFS in >37.5 g/L group were still better than those in ≤37.5 g/L group (both P = 0.002). Multivariate analysis showed that albumin was an independent influencing factor for OS ( RR = 0.419, 95% CI 0.266-0.660, P < 0.001) and PFS ( RR = 0.493, 95% CI 0.322-0.755, P < 0.001). After PSM, albumin was still an independent influencing factor for OS ( RR = 0.305, 95% CI 0.156-0.598, P = 0.001) and PFS ( RR = 0.341, 95% CI 0.185-0.627, P = 0.001). The prognostic prediction performance of the IPI, KPI and PINK models incorporating albumin were all improved. Conclusions:Pretreatment albumin is an important prognostic indicator for ENKTL.

Pretreatment evaluation of 18F-FDG PET-CT in extranodal NK/T-cell lymphoma / 中华肿瘤杂志

Objective: To investigate the clinical value of pretreatment 18F-fluorodeoxy glucose positron emission tomography/computed tomography (18F-FDG PET-CT) in extranodal NK/T-cell lymphoma. Methods: Eighty-one patients with pathologically confirmed extranodal NK/T-cell lymphoma and pretreatment with PET-CT scan in Cancer Hospital, Chinese Academy of Medical Sciences from August 2006 to December 2017 were enrolled in the study. The clinical, follow-up and imaging data were analyzed retrospectively. The relationship between maximum standard uptake value (SUVmax) and prognosis were evaluated by Mann-Whitney U test and Spearman rank correlation analysis. Results: Among the 81 patients, 98.8% (80/81) were upper aerodigestive tract (UAT) involved. Lesions at extra-UAT sites were detected in 7 cases, involving parotid gland (n=1), breast (n=1), spleen (n=1), pancreas (n=1), skin and subcutaneous soft tissue (n=1), muscle (n=1), lung (n=2) and bone (n=3). Lymph node involvement were demonstrated in 33 cases. All of the lesions had increased uptake of PET, the median SUVmax was 8.6. PET-CT changed staging in 15 cases, and 12 cases were adjusted treatment methods. 21 cases were changed radiotherapy target because of PET-CT. The 1-, 2-year progression-free survival (PFS) rates were 88.7% and 80.3% while 1-, 2-year overall survival (OS) rates were 97.2% and 94.4% respectively. The median SUVmax of patients with local lymph nodes involvement was significantly higher than those without local lymph nodes involvement (P=0.007). The SUVmax was positively associated with Ann Arbor stage (r=0.366, P=0.001), lactate dehydrogenase (r=0.308, P=0.005) and Ki-67 level (r=0.270, P=0.017). The SUVmax was inversely associated with lymphocyte count (r=-0.324, P=0.003) and hemoglobin content (r=-0.225, P=0.043). Conclusions: Extranodal NK/T-cell lymphoma predominantly occurs in extra-nodal organs, mainly in the upper respiratory and gastrointestinal tracts, with marked FDG-addiction. Compared with conventional imaging, 18F-FDG PET-CT is sensitive and comprehensive in detecting extra-nodal NK/T-cell lymphoma involvement, assisting in accurate clinical staging and treatment planning. Pretreatment SUVmax is potential for prognosis evaluation since it is correlated with prognostic factors.

Extranodal NK/T-cell lymphoma, nasal type with extensive cardiopulmonary involvement

Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT) is a rare type of Non-Hodgkin's lymphoma, which usually presents with extranodal involvement and affects the nasal/upper aerodigestive tract in the classical presentation. Herein, we report the case of a 31-year-old, previously healthy, male patient diagnosed with ENKTL-NT with the involvement of the lung parenchyma and heart. Unfortunately, due to the rapid disease progression, the diagnosis was performed only at the autopsy. The authors highlight the rare clinical presentation of this type of lymphoma, as well as the challenging anatomopathological diagnosis in necrotic samples.

Prognostic value of absolute lymphocyte count in patients with extranodal nasal NK/T cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the relationship between absolute lymphocyte count (ALC) and prognosis of extranodal nasal NK/T cell lymphoma (ENKTL).Methods:The data of 184 patients with ENKTL who were admitted to Shanxi Provincial Cancer Hospital and the Second People's Hospital of Datong in Shanxi Province from January 2002 to December 2018 were retrospectively analyzed. Contal-O'Quigley variable point method was used to calculate the optimal cut-off value of ALC for predicting the prognosis of ENKTL, and the patients were divided into two groups based on this value. Kaplan-Meier method was used to analyze the survival of the two groups of patients. Cox proportional hazard regression model was used for univariate and multivariate survival analyses.Results:According to the Contal-O'Quigley variable point method, the best cut-off value of ALC for predicting ENKTL prognosis was 1.5×10 9/L. According to this value, patients were divided into ALC>1.5×10 9/L group (98 cases) and ALC≤1.5×10 9/L group (86 cases). Compared with the ALC≤1.5×10 9/L group, the proportions of patients with Eastern Cooperative Oncology Group (ECOG) score ≥2 points, serum lactate dehydrogenase (LDH)> 245 U/L, Korean prognostic index (KPI) score 2-4 points and international prognostic index (IPI) score 2-5 points were lower in the ALC>1.5×10 9/L group, but the proportion of patients with hemoglobin > 120 g/L was higher (all P < 0.05). The overall survival (OS) and progression-free survival (PFS) in the ALC>1.5×10 9/L group were better than those in the ALC≤1.5×10 9/L group (3-year OS rate: 65.7% vs. 45.4%, 5-year OS rate: 61.0% vs. 36.6%; 3-year PFS rate: 61.7% vs. 41.0%, 5-year PFS rate: 51.9% vs. 32.2%; all P < 0.05). Multivariate Cox regression analysis showed that ECOG score, serum LDH level, ALC, radiotherapy and L-asparaginase-containing chemotherapy were independent influencing factors of OS and PFS (all P < 0.05), and for OS, when ALC>1.5×10 9/L compared with≤1.5×10 9/L, RR was 0.634 (95% CI 0.398-1.008, P=0.050), and for PFS, RR was 0.625 (95% CI 0.406-0.962, P=0.033). Conclusion:Patients with high ALC have good prognosis, and therefore ALC may be a powerful prognostic factor of ENKTL.

Sepsis por escherichia coli de inicio infrecuente en paciente con linfoma de células T y NK / Sepsis By Escherichia Coli Of Uncommon Starting In Patient With T And NK Cell Lymphoma

La sepsis se da en presencia de un foco infeccioso; en este caso por Escherichia coli (E.coli), las cuales poseen toxinas que pueden causar daños severos en la funcionalidad y morfología del organismo, viéndose empeorado en pacientes con enfermedades que afecten al sistema inmunitario; como es este caso en presencia de neoplasia hematológica. Paciente femenina de 42 años , con diagnóstico de Linfoma no Hodgkin de células T-NK presenta una placa necrótica en el paladar, temperatura por encima de 38°C, frecuencia respiratoria superando las 20 respiraciones por minutos y frecuencia cardíaca superando los 90 latidos por minuto, al examen de cultivo faríngeo positivo a E.coli, urocultivo negativo, confirmando punto partida infeccioso faríngeo; tratada con amikacina vía endovenosa durante 7 días con buena respuesta a la antibioticoterapia . Se reporta un caso infrecuente por este tipo de bacteria en zona bucal y revisión del tema.

Sepsis occurs in the presence of an infectious focus; in this case by Escherichia coli (E. coli), that toxins can cause severe damage to the organism's functionality and morphology, being worsened in patients with diseases that affect the immune system; as is this case in the presence of hematological malignancy. A 42-year-old female patient with a diagnosis of T-NK non-Hodgkin lymphoma presented with a necrotic plaque on the palate, temperature above 38 ° C, respiratory rate exceeding 20 breaths per minute, and heart rate exceeding 90 beats per minute. , on examination of a positive pharyngeal culture for E. coli, negative urine culture, confirming a pharyngeal infectious starting point; Treat with amikacin endovenously for 7 days with good response to antibiotic therapy. An infrequent case is reported for this type of bacteria in the oral area and a review of the subject.

Linfoma de células T/NK extranasal primario en íleon / Natural Killer/T cell primary extranasal ileum lymphoma

RESUMEN El linfoma extranodal de células T/NK extranasal (NKTL) primario del tracto gastrointestinal es poco frecuente y tiene carácter agresivo. Presentamos el caso de un paciente inmunocompetente de 51 años que ingresa por dolor abdominal de dos meses de evolución. En la colonoscopía, se hallaron ulceraciones ileales, por lo que se le realizaron estudios para descartar enfermedad de Crohn y tuberculosis intestinal, posteriormente presentó obstrucción intestinal. En la laparotomía exploratoria, se encontró un conglomerado ganglionar en mesenterio. La anatomía patológica confirmó el diagnóstico de NKTL primario en íleon. Se inició quimioterapia y el paciente pidió alta voluntaria dada su precaria condición. Dos meses después del alta el paciente fallece. Este linfoma ha sido reportado principalmente en Asia y posiblemente sea el primer caso reportado en Perú. Tiene un pronóstico funesto con una supervivencia global de ocho meses. Por ello, es necesario un diagnóstico precoz e iniciar la terapia oportunamente.

ABSTRACT Primary extranodal Natural Killer / T cell lymphoma (NKTL) on gastrointestinal tract is an uncommon and aggressive neoplasm. We present the case of a 51-year-old immunocompetent patient with a 2-month history of abdominal pain. Colonoscopy findings showed ileal ulcerations, so studies were carried out to rule out Crohn's disease and intestinal tuberculosis. Later, he developed intestinal obstruction. Exploratory laparotomy found a nodal conglomerate in the mesentery. Anatomical pathology confirmed the diagnosis of primary NKTL on the ileum. Chemotherapy was initiated but the patient asked for voluntary discharge because of his precarious condition. Two months after discharge the patient died. This lymphoma has been reported mainly in Asia and is possibly the first case in Peru. It has a dismal prognosis with overall survival of 8 months. Therefore, it is necessary to get an early diagnosis and begin therapy in a timely manner.

14-3-3ζ protein mediates gemcitabine resistance in NK/T-cell lymphoma / 中华血液学杂志

Objective: To explore the molecular mechanisms of 14-3-3ζ in gemcitabine resistance in extranodal NK/T-cell lymphoma, nasal type (ENKTL) . Methods: The effects of cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and transwell assay. YTS cells were exposed to gradually increased concentrations of gemcitabine to establish gemcitabine-resistant YTS cells (YTS-gem) in vitro. 14-3-3ζ specific siRNA lentiviral vector was transfected into YTS and YTS-gem cells to downregulate 14-3-3ζ expression, and stable transfected cell clones were screened. The protein expression was determined by Western blot. Results: ①14-3-3ζ expression was significantly up-regulated in gemcitabine resistant YTS-gem cells, comparing with that of YTS cells (P<0.05) . ②The results of CCK-8 and transwell assay showed that downregulation of 14-3-3ζ significantly reduced the cell proliferation and invasion abilities (P<0.05) . ③Downregulation of 14-3-3ζ could restore gemcitabine sensitivity in gemcitabine resistant YTS-gem cells (P<0.05) . ④Western blotting results showed that knockdown of 14-3-3ζ significantly upregulated pro-apoptotic Bax, and downregulated anti-apoptotic Bcl-2, Caspase-3, cleaved caspase-3, Cyclin D1 in gemcitabine-resistant YTS-gem cells (P<0.05) . There was no significant difference in p53 ang P-gp expression levels. Conclusions: 14-3-3ζ was upregulated in gemcitabine resistant YTS cells. Overexpression of 14-3-3ζ promoted cell proliferation and enhanced cell migration. 14-3-3ζ contributed to gemcitabine resistance to ENKTL through anti-apoptosis.