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Purpose: Lymphoma has become a major threat to human health. Fortunately, the diagnosis and treatment of lymphoma have developed rapidly, and research progress has emerged in an endless stream, with new drugs emerging one after another. These results are constantly rewriting guidelines changing clinical practice, need to be popularized and applied more widely. Methods: This guideline has integrated consensuses reached by the Lymphoma Committee of China Anti-Cancer Association (CACA), based on China's practice, tracking previous results of the most advanced clinical researches, absorbing the latest clinical evidence, and referring to domestic and international lymphoma guidelines. Results: This holistic integrative guideline of lymphoma introduces the latest progress in the diagnosis and treatment of different subtypes of lymphoma, guide the clinical application of new drugs, standardized and precise management for lymphoma patients. Conclusions: CACA guidelines for holistic integrative management of lymphoma (version 2022) enhance standardization and precision of the management for lymphoma patients in China. [ABSTRACT FROM AUTHOR]

Summary: Anti‐PD‐1 antibody has shown certain effects in patients with newly diagnosed extranodal NK/T‐cell lymphoma (ENKTL). Here, we evaluated the clinical efficacy and safety of first‐line anti‐PD‐1 antibody for the treatment of patients with ENKTL and explored biomarkers for treatment response. The clinical data of 107 patients with newly diagnosed ENKTL were retrospectively analysed. Patients received either first‐line anti‐PD‐1 antibody induction treatment or anti‐PD‐1 antibody combined with asparaginase‐based chemotherapy (immunochemotherapy). We found that immunochemotherapy was an independent prognostic factor for longer PFS (p < 0.001). The overall response rate and complete remission rate of immunochemotherapy group was higher than immunotherapy induction group (86.11% vs. 62.86% and 72.22% vs. 52.29%, respectively, p = 0.013). We also observed pretreatment CD4/CD8 ratio >0.83 was significant associated with better response and longer PFS in ENKTL patients received first‐line anti‐PD1‐antibody. Plasma copy number of EBV decreased more significantly in patients with CD4/CD8 ratio >0.83 after treatment. PD‐L1 expression was associated with better response and PFS, while elevated plasma IL‐6, IL‐10 and IFN‐γ were associated with poor prognosis. Anti‐PD‐1 antibody treatment showed promising results in newly diagnosed ENKTL patients. The assessment of pretreatment CD4/CD8 ratio in ENKTL seems feasible for identifying responders to anti‐PD‐1 antibody treatment. [ABSTRACT FROM AUTHOR]

Extranodal natural killer (NK)/T‐cell lymphoma (ENKTL) is strongly associated with Epstein–Barr virus (EBV) and has a high prevalence in Asian and in Central and South America. About 85% of ENKTLs derive from NK cells and 15% from T‐cells. Various factors have been implicated in the development of ENKTL. Molecular pathogenesis of NK/T‐cell lymphomas include mutations of genes, involving in the Janus Kinase/signal transducer and activator of transcription pathway, RNA helicase family, epigenetic regulation, and tumor suppression. The relationship between ENKTL and human leukocyte antigen has been demonstrated. Radiotherapy plays a key role in the first‐line treatment of early‐stage. In stage III/IV diseases, non‐anthracycline‐regimens‐containing L‐asparaginase are recommended. Although clinical remission after L‐asparaginase‐based combination therapy has been achieved in the majority of patients with advanced‐stage or relapsed/refractory extranodal NK/T‐cell lymphoma‐nasal type, the long‐term overall survival is still poor. Recently, immunotherapy and new therapeutic targets have gained much attention. In this article, we discuss the pathogenesis, diagnosis, prognostic models and management options of ENKTL. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to estimate the health preference–based index scores of the population of patients with lymphoma using the EQ-5D in China. Methods: A cross-sectional online survey was conducted to examine the health and well-being of patients with lymphoma in China. Their health-related quality of life (HRQoL; using the EQ-5D), demographic and socioeconomic characteristics, and health conditions were assessed. The data were analyzed using Pearson's χ2 test, analysis of variance, and binary logistic and Tobit regression models. Results: A total of 3261 patients (sex: men = 58.5%, age: < 30 years = 9.5% and > 60 years = 24.6%) participated in the study. The mean EQ-5D-5L index and EQ-VAS scores were 0.83 and 68.8, respectively. Binary logistic regression analysis revealed that women reported more pain-related problems than men did. Unemployed participants were substantially more likely to report health problems on all the five dimensions of the EQ-5D than their employed counterparts. The Tobit regression model revealed that respondents who were older, unemployed, with low income, received chemotherapy, and with short durations reported a low index score. Conclusion: Using the EQ-5D, the preference-based scores of different subpopulations of patients with lymphoma may support economic evaluation by promoting the simultaneous consideration of both the reasonable use of resources and satisfactory achievement of health outcomes. [ABSTRACT FROM AUTHOR]

Background: Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL. Methods: This phase 2 study with Simon's two-stage design evaluated daratumumab in patients with histologically confirmed extranodal NKTCL, nasal type, per WHO classification that was refractory to or relapsed after ≥ 1 line of chemotherapy, who were not candidates for other treatment modalities. All patients received daratumumab 16 mg/kg intravenously once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter until progression or unacceptable toxicity; all cycles were 28 days. The primary end point was objective response rate (ORR) based on blinded independent central review per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification). Results: In total, 32 Asian patients received daratumumab. The ORR was 25.0% (95% confidence interval [CI] 11.5–43.4); all 8 responders had a partial response; and the median duration of response was 55.0 days (95% CI 29–339). At 10.2 months of median follow-up, median progression-free survival (PFS) was 53.0 days (95% CI 43–106); the 4-month PFS rate was 13.0%. Median overall survival (OS) was 141.0 days (95% CI 94–438); the 6-month OS rate was 42.9%. Nineteen (59.4%) patients had grade 3/4 treatment-emergent adverse events (TEAEs); the most common was thrombocytopenia (25.0%; n = 8). TEAEs leading to death occurred in 4 patients (death, respiratory failure, septic shock, and pneumonia); all were unrelated to daratumumab. Conclusions: In patients with R/R NKTCL, daratumumab monotherapy was well tolerated with no new safety concerns and achieved an ORR of 25.0%. However, no patients achieved complete response, and duration of response was short. Trial registration ClinicalTrials.gov, NCT02927925. Registered 7 October 2016. [ABSTRACT FROM AUTHOR]

Objectives: Extranodal natural/killer T-cell lymphoma (ENKTL) is a rare subtype of T cell non-Hodgkin's lymphoma. Current clinical prognostic models for ENKTL still have their limitations. Validated prognostic models for ENKTL have not yet been established. Methods: Tumor microenvironment IL-6 was measured by immunohistochemistry in 78 ENKTL patients. Results: Patients with negative IL-6 expression in the tumor microenvironment have a longer PFS (56.0 months vs. 25.6 months, p < 0.001) and OS (96.0 months vs. 43.3 months, p < 0.001). In the multivariate analysis, tumor microenvironment IL-6 [p = 0.048, HR = 1.76(1.00-3.08)] and extranodal involvement [p = 0.001, HR = 2.69(1.50-4.82)] were independent prognostic factors for PFS. Tumor microenvironment IL-6 [p = 0.033, HR = 2.69 (1.08-6.67)], Ann Arbor stage [p = 0.002, HR = 2.77 (1.47-5.23)] and B symptom [p = 0.027, HR = 2.02 (1.08-3.78)] were independent prognostic factors for OS. Expert opinion: A high IL-6 expression was related to poor survival, which may be a valuable biomarker for prognostic evaluation at baseline in ENKTL. These results showed that anti-IL-6R may be a potential targeted therapy for the treatment of advanced or relapsed ENKTL. [ABSTRACT FROM AUTHOR]

Background: This Phase 3 randomized, double-blind study evaluated the efficacy and safety of plerixafor plus granulocyte-colony-stimulating factor for the mobilization of hematopoietic stem cells in Chinese patients with non-Hodgkin's lymphoma.Study Design and Methods: Adults (ages 18-75 years) with non-Hodgkin's lymphoma in first or second complete or partial remission, without previous hematopoietic stem cell mobilization or autologous transplant, were included. Patients received granulocyte-colony-stimulating factor 10 µg/kg/day from Days 1 through 4 before they were randomized (1:1) to receive either plerixafor 0.24 mg/kg/day or placebo subcutaneously on Days 4 through 7 plus continued granulocyte-colony-stimulating factor on Days 5 through 8. Apheresis began on Day 5 and continued for no more than 4 days. The primary endpoint was collection of 5 × 106 CD34+ cells/kg or greater over no more than 4 days of apheresis. Other endpoints included the collection of 2 × 106 CD34+ cells/kg or greater and safety.Results: Overall, 101 patients were enrolled, and 50 were randomized to each group. More patients in the plerixafor group achieved 5 × 106 CD34+ cells/kg or greater (62 vs. 20%; p < 0.0001) or 2 × 106 CD34+ cells/kg or greater (88 vs. 66%) and underwent transplantation (88 vs. 68%) compared with those in the placebo group. The most common plerixafor-related adverse events were nausea (7.8%) and diarrhea (3.9%).Conclusion: Plerixafor plus granulocyte-colony-stimulating factor is superior to placebo plus granulocyte-colony-stimulating factor for the mobilization of CD34+ cells for autologous transplantation and is generally well tolerated in Chinese patients with non-Hodgkin's lymphoma. [ABSTRACT FROM AUTHOR]

Prophylactic antiviral therapy is essential for lymphoma patients with high baseline HBV DNA who undergo cytotoxic chemotherapy. However, there are limited data on the optimal options. The present study was designed to compare the efficacy of prophylactic lamivudine (LAM) with lamivudine plus adefovir dipivoxil (LAM+ADV) in preventing hepatitis B virus (HBV) reactivation in lymphoma with, pre-chemotherapy HBV DNA load ≥2000 IU/ml. We retrospectively analyzed the medical records of 86 lymphoma patients with baseline HBV DNA load ≥2000 IU/ml during chemotherapy and received LAM or LAM+ADV as prophylaxis between January 1, 2008 and November 30, 2014 at Sun Yat-sen University Cancer Center, China. Sixty-five patients received LAM and 21 received LAM+ADV. The rate was significantly lower in the LAM+ADV group compared with the LAM group for HBV reactivation (23.8% vs 55.4%; p = 0.012), while no difference was observed between the two groups in patients for HBV-related hepatitis (21.3% vs 33.3%; p   =  0.349), and chemotherapy disruption (10.9% vs 19.0%; p = 0.337). In a multivariate analysis of factors associated with HBV reactivation in these patients, LAM+ADV treatment and HBeAg negative were the independent protective factors. Therefore, LAM+ADV should be considered for antiviral prophylaxis in lymphoma patients with pre-chemotherapy HBV DNA load ≥2000 IU/ml. Further study is warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Many studies have demonstrated that tumor-associated macrophages (TAMs) were a prognostic indicator in patients with B cell lymphoma. But, we know little about the clinical significance of TAMs in extranodal natural killer/T cell lymphoma(ENKTL), nasal type. CD68 expression was detected using immunohistochemistry to determine the numbers of TAMs in 70 ENKTL patients, and the data were used to evaluate its relationship with clinicopathological features, treatment response, and prognosis. Patients with high number of infiltrated CD68+ TAMs (>60/hpf) at diagnosis tended to have more adverse clinical characteristics. Patients with low CD68+ TAM content (<60/hpf) at diagnosis had better overall survival ( P = 0.003) and progression-free survival ( P = 0.002) and achieved higher complete remission rates ( P = 0.008). Multivariate analysis revealed that CD68 + TAM content, Ki-67 index, and stage III and IV were independent prognostic factors for both OS and PFS. Using the International Prognostic Index or Korean Prognostic Index for extranodal NK/T cell lymphoma, nasal type, the majority of patients were in the low-risk category. CD68 + TAM content was helpful to differentiate the low-risk patients with different survival outcomes. Our data suggest that CD68+ TAM content at diagnosis is a powerful predictor of prognosis for ENKTL, which suggests a role for TAMs in the pathogenesis of this disease and offers new insight into potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma in the world. Clinically, biologically, and pathologically, DLBCL is a heterogeneous entity with a range of potential outcomes. Immunochemotherapy regimens, consisting of the chimeric monoclonal anti-CD20 antibody rituximab in combination with chemotherapy, have improved the outcomes. Relapsed DLBCL is generally treated with salvage immunochemotherapy followed by high-dose therapy and autologous stem cell transplantation; however, DLBCL is not yet curable in up to a third of patients. The real promise for cure lies in novel agents and their rational combinations. The improved understanding of DLBCL subtypes and gene expression profiling has led to the identification of targeted drugs that may allow for subtype specific therapy. We have summarized the existing data on the prognostic factors and the treatment of DLBCL, including the use of novel agents such as lenalidomide, carfilzomib, and ibrutinib. We also share our thoughts on the direction of future clinical trials. [ABSTRACT FROM AUTHOR]

13-Methyltetradecanoic acid (13-MTD), a saturated branched-chain fatty acid purified from soy fermentation products, induces apoptosis in human cancer cells. We investigated the inhibitory effects and mechanism of action of 13-MTD on T-cell non-Hodgkin’s lymphoma (T-NHL) cell lines both in vitro and in vivo. Growth inhibition in response to 13-MTD was evaluated by the cell counting kit-8 (CCK-8) assay in three T-NHL cell lines (Jurkat, Hut78, EL4 cells). Flow cytometry analyses were used to monitor the cell cycle and apoptosis. Proteins involved in 13-MTD-induced apoptosis were examined in Jurkat cells by western blotting. We found that 13-MTD inhibited proliferation and induced the apoptosis of T-NHL cell lines. 13-MTD treatment also induced a concentration-dependent arrest of Jurkat cells in the G1-phase. During 13-MTD-induced apoptosis in Jurkat cells, the cleavage of caspase-3 and poly ADP-ribose polymerase (PARP, a caspase enzymolysis product) were detected after incubation for 2 h, and increased after extending the incubation time. However, there was no change in the expression of Bcl-2 or c-myc proteins. The appearance of apoptotic Jurkat cells was accompanied by the inhibition of AKT and nuclear factor-kappa B (NF-κB) phosphorylation. In addition, 13-MTD could also effectively inhibit the growth of T-NHL tumors in vivo in a xenograft model. The tumor inhibition rate in the experimental group was 40%. These data indicate that 13-MTD inhibits proliferation and induces apoptosis through the down-regulation of AKT phosphorylation followed by caspase activation, which may provide a new approach for treating T-cell lymphomas. [ABSTRACT FROM AUTHOR]

• PBMC EBV-DNA poorly correlated with imaging-based disease assessment and plasma EBV-DNA in patients with ENKTCL, while Plasma EBV-DNA strongly correlated with disease status. • Plasma EBV-DNA was more sensitive than PET/CT and CT/MRI in response evaluation and relapse monitoring. Regardless of imaging-based assessment, a substantial increase of plasma EBV-DNA indicated disease progression during treatment, and relapse was almost inevitable in patients with positive plasma EBV-DNA at the end of treatment. • When imaging-based disease assessment was discordant with plasma EBV-based assessment, the kinetic patterns of EBV-DNA were helpful to identify at-risk patients. Relapse occurred only in patient with intermittently or persistently positive plasma EBV-DNA, and occasionally positive EBV-DNA did not correlate with relapse. Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related hematological malignancy. The presence of EBV-DNA in peripheral blood is a widely used ENKTCL tumor marker. However, there is no consensus on the preferred blood specimen type for EBV testing. Furthermore, discordance between EBV-based and imaging-based disease assessments is common, and how to interpret this discordance is important. We retrospectively analyzed the data of ENKTCL patients in the Affiliated Cancer Hospital of Zhengzhou university and Sun Yat-sen University Cancer Center. All EBV-DNA and imaging-based disease assessment data were collected at diagnosis, during treatment, at the end of treatment, and during follow-up. We compared matched plasma EBV-DNA and peripheral blood mononuclear cell (PBMC) EBV-DNA and matched EBV-based and imaging-based assessments to uncover their clinical relevance. A total of 450 patients with adequate data were included, of whom 278 had plasma EBV-DNA data, 250 had PBMC EBV-DNA data, and 78 had matched plasma and PBMC EBV-DNA data. No significant correlations were found between PBMC and plasma EBV-DNA and between PBMC EBV-DNA and imaging-based assessment, but patients with positive PBMC EBV-DNA at diagnosis or intermittently/persistently positive PBMC EBV-DNA during follow-up had poorer survival. In contrast, plasma EBV-DNA strongly correlated with lymphoma status. Detectable pre- and post-treatment plasma EBV-DNA was associated with significantly worse survival. Patients with early-stage disease who had detectable plasma EBV-DNA at the end of treatment shared similar survival to those with advanced-stage disease, even if their imaging-based assessments were negative. For disease relapse monitoring, 78 (55.7%) episodes of relapse were detected by both imaging and plasma EBV-DNA; 58 (41.4%) detected by plasma EBV-DNA earlier than imaging, with a median time of 9.3 (0.3 - 37.8) months; and only 4 (2.9%) detected by plasma EBV-DNA later than imaging. The sensitivities of plasma EBV-DNA, PET/CT, and CT/MRI were 97.1%, 76.8%, and 45.1%, respectively, and their specificities were 91.7%, 84.2%, and 96.7%, respectively. Analysis of EBV kinetic patterns in EBV+/imaging- episodes revealed that relapse occurred only in patients with intermittently/persistently positive plasma EBV-DNA. Persistent plasma EBV+ was also seen in patients after autologous hematopoietic stem cell transplantation. Occasional EBV+ was not associated with relapse. Plasma and PBMC EBV-DNA have different clinical relevance in ENKTCL patients. PBMC EBV-DNA does not correlate with imaging-based disease assessment. PBMC or even whole blood should not be used for response evaluation and relapse monitoring. However, PBMC EBV-DNA still has prognostic value. Plasma EBV-DNA is strongly related to tumor status and is not only a prognosticator at diagnosis and end of treatment, but also a sensitive marker in relapse monitoring compared to PET/CT and CT/MRI. The specificity of plasma EBV-DNA is relatively low, but when EBV-DNA kinetic patterns are considered, it can identify at-risk patients. [ABSTRACT FROM AUTHOR]