The experience of diagnosis and treatment for TAFRO syndrome.

Early identification, diagnosis and treatment of TAFRO syndrome are very importants. We retrospectively analysed 6 patients with TAFRO syndrome. Their clinical manifestations, treatment methods, survival and other aspects were summarized. All patients were pathologically diagnosed with Castleman's disease, with fever, an inflammatory storm state and varying degrees of anasarca. All patients received steroid therapy; four of them also received chemotherapy, and 1 received rituximab. Of the 3 patients with severe disease, only 1 patient who received the recommended dose of glucocorticoids survived. Early administration of glucocorticoids can improve the prognosis, especially in patients with severe disease, and adequate glucocorticoids are important.

Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study.

BACKGROUND: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. METHODS: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. RESULTS: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. CONCLUSION: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.

c-Myc mediated upregulation of long noncoding RNA SNHG12 regulates proliferation and drug sensitivity in natural killer/T-cell lymphoma.

Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy with poor outcomes. The treatment of NKTCL requires intensive chemotherapy. Long noncoding RNAs (lncRNAs) have been implicated in many cancers, including NKTCL. The elucidation of the multidrug resistance (MDR) may greatly contribute to explore novel therapeutic strategies. Herein, we explored the roles and potential regulatory mechanism of lncRNAs small nucleolar RNA host gene 12 (SNHG12) in MDR of NKTCL. We found that SNHG12 was upregulated in NKTCL tissue sections, and its high expression was positively correlated with clinical grade of malignancy of NKTCL. c-Myc and SNHG12 expression was upregulated in NKTCL cell lines. c-Myc- and SNHG12 overexpression promoted proliferation and inhibited sensitivity to cisplatin (CDDP) in NK/T-cell lymphoma cell line YTS cells, and c-Myc and SNHG12-downregulation inhibited proliferation and enhanced sensitivity to CDDP in SNK-6 cells. Moreover, c-Myc- and SNHG12 overexpression increased Ki67 and P-gp expression in YTS cells, whereas c-Myc and SNHG12-downregulation reduced the Ki67 and P-gp expression in SNK-6 cells. Correlational analyses revealed that c-Myc expression was positively correlated with SNHG12 expression in NKTCL tissues. Mechanism research showed that SNHG12 was a direct transcriptional target of c-Myc and c-Myc promoted SNHG12 expression in NKTCL cell lines. Further research showed that SNHG12 overexpression reversed the effects of c-Myc downregulation on proliferation and sensitivity to CDDP in NKTCL cell lines. Taken together, our findings first report that c-Myc mediated upregulation of SNHG12 promotes proliferation and inhibits drug sensitivity in NKTCL, which provides new insights into the therapeutic target for NKTCL.

TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/ß-catenin pathway.

BACKGROUND: Esophageal carcinoma is the eighth prevalent malignancy and ranks the sixth in carcinoma-related death worldwide. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) has been identified as a tumor suppressor in multiple carcinomas. However, its roles and molecular mechanisms underlying esophageal carcinoma progression are still undefined till now. METHODS: RT-qPCR assay was employed to detect the expression of TIPE2 mRNA. TIPE2 protein expression was measured by using western blot assay. Ad-V and Ad-TIPE2 adenoviruses were constructed to overexpress TIPE2. The effects of TIPE2 overexpression on cell proliferation, invasion and apoptosis were assessed by MTT and Edu incorporation assays, transwell invasion assay and flow cytometry analysis, respectively. The effect of TIPE2 overexpression on xenograft tumor growth was determined by measuring tumor volume and weight, together with immunohistochemistry assay. The effect of TIPE2 overexpression on the Wnt/ß-catenin signaling pathway was evaluated by detecting the protein levels of ß-catenin, c-Myc and cyclinD1 in EC9076 cells and xenograft tumors of esophageal carcinoma. RESULTS: TIPE2 expression was downregulated in esophageal carcinoma tissues and cells. Adenovirus-mediated TIPE2 overexpression suppressed cell proliferation and invasion, and induced apoptosis in esophageal carcinoma cells. Enforced expression of TIPE2 inhibited tumor growth in vivo, as evidenced by the reduced tumor volume, tumor weight and proliferating cell nuclear antigen expression. Overexpression of TIPE2 inhibited the Wnt/ß-catenin signaling pathway in esophageal carcinoma in vitro and in vivo. CONCLUSIONS: These results suggest that TIPE2 suppressed progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/ß-catenin pathway.

COD removal efficiency and mechanism of HMBR in high volumetric loading for ship domestic sewage treatment.

The hybrid membrane bioreactor (HMBR) has been applied in ship domestic sewage treatment under high volumetric loading for ship space saving. The mechanism and influence factors on the efficiency, including hydraulic retention time (HRT), dissolved oxygen (DO) of chemical oxygen demand (COD) removal were investigated. The HMBR's average COD removal rate was up to 95.13% on volumetric loading of 2.4 kgCOD/(m3•d) and the COD concentration in the effluent was 48.5 mg/L, far below the International Maritime Organization (IMO) discharge standard of 125 mg/L. DO had a more remarkable effect on the COD removal efficiency than HRT. In addition, HMBR revealed an excellent capability of resisting organics loading impact. Within the range of volumetric loading of 0.72 to 4.8 kg COD/(m3•d), the effluent COD concentration satisfied the discharge requirement of IMO. It was found that the organics degradation in the aeration tank followed the first-order reaction, with obtained kinetic parameters of vmax (2.79 d-1) and Ks (395 mg/L). The original finding of this study had shown the effectiveness of HMBR in organic contaminant degradation at high substrate concentration, which can be used as guidance in the full scale of the design, operation and maintenance of ship domestic sewage treatment devices.

[Potential Ecological Suitability Regionalization Analysis of Angelica sinensis Based on GIS and Fuzzy Matter Element Model].

OBJECTIVE: To study the potential ecological suitability regionalization of Angelica sinensis, for protecting wild resources and selecting cultivation location and designing rational production layout. METHODS: Based on fuzzy matter element model, the relationship of fuzzy membership function between ferulic acid content and 14 ecological factors, including climate, topography and soil,were established. Then information entropy theory was used to determine the relative importance of each environmental factor, and thus to determine the most limiting habitat criteria. Finally, the probable spatial distribution of Angelica sinensis across ten provinces in Western China was determined based on GIS spatial analysis of habitat conditions. Meanwhile, the optimal index range of ecological factors was quantified. RESULTS: It was showed that the percentage of moderately and highly suitable habitats for Angelica sinensis in the study area was 9. 64%, its area was 306,768. 01 km2. The moderately and highly suitable habitats were mainly located in the southeast of Gansu ind Tibet,the north of Sichuan and the northwest of Yunnan. The results also showed that six dominant ecological factors controlling the distribution of Angelica sinensis. These six dominant features were as follows: (1) mean temperature of wettest quarter, (2) altitude, (3) precipitation of growth, (4) annual relative humidity, (5) average temperature of growth period, and (6) annual )recipitation. CONCLUSION: The habitat suitability assessment model based on GIS and fuzzy matter element model theory can accurately valuate the habitat suitability of Angelica sinensis, quantify the area of suitable habitat and analyze the spatial distribution. This informaion is of value to provide insight for choosing the most suitable cultivation sites,as well as the habitat protection zones.

Diffusion models in text generation: a survey.

Diffusion models are a kind of math-based model that were first applied to image generation. Recently, they have drawn wide interest in natural language generation (NLG), a sub-field of natural language processing (NLP), due to their capability to generate varied and high-quality text outputs. In this article, we conduct a comprehensive survey on the application of diffusion models in text generation. We divide text generation into three parts (conditional, unconstrained, and multi-mode text generation, respectively) and provide a detailed introduction. In addition, considering that autoregressive-based pre-training models (PLMs) have recently dominated text generation, we conduct a detailed comparison between diffusion models and PLMs in multiple dimensions, highlighting their respective advantages and limitations. We believe that integrating PLMs into diffusion is a valuable research avenue. We also discuss current challenges faced by diffusion models in text generation and propose potential future research directions, such as improving sampling speed to address scalability issues and exploring multi-modal text generation. By providing a comprehensive analysis and outlook, this survey will serve as a valuable reference for researchers and practitioners interested in utilizing diffusion models for text generation tasks.

The relationship and clinical significance of serum cytokine expression level and skin pruritus in patients with Hodgkin lymphoma and angioimmunoblastic T-cell lymphoma.

Pruritus of lymphoma is commonly associated with both Hodgkin lymphoma (HL) and angioimmunoblastic T cell lymphoma (AITL) and critically affects the life quality of patient. Recent evidence suggests that the pruritogenic cytokines seem to play a significant role in the genesis of chronic. This study aims to investigate the cytokines associated with itching in lymphoma patients and provide the basis for potential therapeutic targets. Serum samples were collected from 60 lymphoma patients, including 47 with Hodgkin lymphoma (HL) and 13 with angioimmunoblastic T-cell lymphoma (AITL), serving as the observation group (lymphoma group, LP group, n = 60). Additionally, serum samples from 8 healthy donors (HD group, n = 8) were collected for comparison. Within the lymphoma group, patients were stratified into those with pruritus (LWP group, n = 30) and those without pruritus (LWOP group, n = 30) based on the presence of skin pruritus symptoms. Elevated levels of multiple cytokines were significantly observed in the LP group in comparison to the HD group (p < 0.01). Patients in LWP group exhibited higher serum levels of IL-31 (p < 0.001), IL-1ß (P = 0.039), and IL-1α (P = 0.037) compared to LWOP group. Notably, serum IL-31 levels were higher in advanced AITL patients (stage IV) than in early AITL patients (stage I-Ⅲ, P < 0.05). In subgroup analysis, patients with pruritus in the AITL group exhibited higher serum levels of MIG and CTACK compared to HL group, whereas PDGF-BB levels were significantly lower (p < 0.05). Elevated serum levels of IL-31, IL-1ß, and IL-1α are linked to lymphoma-associated pruritus. Differences in serum cytokine profiles between HL and AITL subgroups are also highlighted. These findings offer valuable insights for clinical intervention in managing lymphoma-related pruritus.

Real-world evidence of ABVD-like regimens compared with ABVD in classical Hodgkin lymphoma: a 10-year study from China.

BACKGROUND: Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) has been regarded as the standard treatment regimen for classical Hodgkin lymphoma. In recent years, ABVD-like regimens, which emerged due to shortages and the lung toxicity of bleomycin or the emergence of immune checkpoint inhibitors and antibody-drug conjugates, may be favorable, but have not yet been tested. METHODS: We compared the outcomes of ABVD with ABVD-like regimens, which include bleomycin was completely or partially omitted; meanwhile, etoposide or PD-1 inhibitors were added. RESULTS: 5-Year progression-free survival (PFS) was higher for ABVD than ABVD-like regimens in young patients (82.1% vs. 67.0%, p = 0.029), patients with serum beta-2 microglobulin (ß2-MG) ≥ 1.85 mg/L (75.8% vs. 57.6%, p = 0.046), and advanced-stage patients with IPS score 4-7(63.1%, 18.3%, p = 0.038). For elderly (60.5% vs.76.1%, p = 0.089), patients with ß2-MG < 1.85 mg/L (83.1% vs 76.1%, p = 0.282), and advanced-stage patients with IPS score 0-3(84.6% vs. 81.3%, p = 0.476), 5-year PFS for ABVD did not differ from ABVD-like regimens. Elderly patients treated with bleomycin-free regimens showed a better survival trend compared with ABVD (99.3% vs. 61.3%, p = 0.270). CONCLUSION: ABVD is superior to ABVD-like regimens in achieving PFS in young patients or patients with poor prognosis including high IPS score and ß2-MG level. ABVD-like regimens are as effective as ABVD in elderly or low-risk patients including low IPS score and ß2-MG level; elderly patients treated with bleomycin-free regimens exhibit a better survival trend compared with ABVD.

Decitabine combined with RDHAP regimen in relapsed/refractory diffuse large B cell lymphoma.

BACKGROUND: There is an urgent need for effective treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R-DLBCL). This trial investigated the efficacy of decitabine in combination with rituximab, cisplatin, cytarabine, dexamethasone (RDHAP) in R/R-DLBCL. METHODS: 56 patients were divided into two groups (decitabine-RDHAP group. n = 35; RDHAP group, n = 21). The primary endpoints were the overall response rate (ORR) and duration of remission (DOR). Secondary objectives were toxicity, progression-free survival (PFS), and overall survival (OS). RESULTS: The ORR was 40% and 33% for decitabine-RDHAP and RDHAP groups, respectively, with no difference between the groups. The DOR for the decitabine-RDHAP regimen was higher than that for the RDHAP regimen (p = 0.044). After a median follow-up of 12.0 months, the median PFS and OS were 7.0 and 17.0 months for in the decitabine-RDHAP group and 5.0 and 9.0 months in the RDHAP group with no significant differences between the two groups (p = 0.47, 0.17). The incidence of adverse events was not significantly different between groups. CONCLUSION: The decitabine-RDHAP regimen is effective and well tolerated, and is a promising salvage regimen for R/R-DLBCL.

Fotemustine, etoposide, cytarabine, and cyclophosphamide (FEAC) conditioning regimen for autologous stem cell transplantation in lymphoma.

To investigate the efficacy and safety of the FEAC (fotemustine, etoposide, cytarabine, and cyclophosphamide) conditioning regimen for the treatment of lymphoma, we retrospectively analyzed the records of 76 Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent autologous stem cell transplantation (ASCT) after the FEAC conditioning regimen. Their survival, as well as the clinical efficacy, hematopoietic engraftment time, and toxicity, were analyzed. One patient died of severe pulmonary infection, and the transplant-related mortality (TRM) was 1.3% (1/76). Hematopoietic engraftment was achieved successfully in the remaining 75 patients. The median times of neutrophil and platelet engraftment were 11 d (6-21 d) and 13 d (8-24 d), respectively. The 2-year progression-free survival (PFS) rate was 69.1%, and the 2-year overall survival (OS) rate was 84.2%. FEAC conditioning regimen has acceptable toxicity, and the prognosis of patients is good, making it a feasible alternative to the BEAM regimen for ASCT.

Clinical and therapeutical significances of the cluster and signature based on oxidative stress for osteosarcoma.

BACKGROUND: It is of great clinical significance to find out the ideal tumor biomarkers and therapeutic targets to improve the prognosis of patients with osteosarcoma (OS). Oxidative stress (OXS) can directly target intracellular macromolecules and exhibit dual effects of tumor promotion and suppression. METHODS: OXS-related genes (OXRGs) were extracted from public databases, including TARGET and GEO. Univariate Cox regression analysis, Random Survival Forest algorithm, and LASSO regression were performed to identify prognostic genes and establish the OXS-signature. The efficacy of the OXS-signature was further evaluated by Kaplan-Meier curves and timeROC package. Evaluation of immunological characteristics was achieved based on ESTIMATE algorithm and ssGSEA. Submap algorithm was used to explore the response to anti-PD1 and anti-CTLA4 therapy for OS. Drug response prediction was conducted by using pRRophetic package. The expression values of related genes in the OXS-signature were detected with PCR assays. RESULTS: Two OXS-clusters were identified for OS, with remarkable differences of clusters presented in prognosis. Kyoto Encyclopedia of Genes Genomes (KEGG) analysis showed that differentially expressed genes (DEGs) between the OXS-clusters were significantly enriched in several immune-related pathways. Patients with lower OS-scores attained better clinical outcomes, and presented more sensitivity to ICB therapy. By contrast, OS patients with higher OS-scores revealed more sensitivity to certain drugs. Furthermore, critical genes, RHBDL2 and CGREF1 from the model, were significantly higher expressed in OS cell lines. CONCLUSIONS: Our study identified the clusters and signature based on OXS, which would lay the foundation for molecular experimental research, disease prevention and treatment of OS.

Inactivation of MYO5B promotes invasion and motility in gastric cancer cells.

BACKGROUND: Loss of cell polarity and tissue disorganisation are hallmarks of cancer. MYO5B mutations disrupt epithelial cell polarity, suggesting that MYO5B may be involved in tumorigenesis. METHODS: We analyzed MYO5B expression in 70 gastric cancer tissues by immunohistochemistry using a tissue microarray method. Two related proteins, Rab11a and TfR, were also investigated. RESULTS: We found that the negative rate of MYO5B was 78.6 and 17.1% in gastric cancer and normal gastric tissues (P < 0.001), respectively. The MYO5B expression had a strong relationship with Rab11a expression (P = 0.002). We also found that inactivation by siRNA against MYO5B promoted the proliferation, invasion and migration of gastric cancer cells. CONCLUSION: The expression of MYO5B was downregulated in gastric cancer and inactivation of MYO5B may contribute to tumorigenesis. Therefore, MYO5B may become an important biomarker for gastric cancer in the future.

Deep learning for aspect-based sentiment analysis: a review.

User-generated content on various Internet platforms is growing explosively, and contains valuable information that helps decision-making. However, extracting this information accurately is still a challenge since there are massive amounts of data. Thereinto, sentiment analysis solves this problem by identifying people's sentiments towards the opinion target. This article aims to provide an overview of deep learning for aspect-based sentiment analysis. Firstly, we give a brief introduction to the aspect-based sentiment analysis (ABSA) task. Then, we present the overall framework of the ABSA task from two different perspectives: significant subtasks and the task modeling process. Finally, challenges are proposed and summarized in the field of sentiment analysis, especially in the domain of aspect-based sentiment analysis. In addition, ABSA task also takes the relations between various objects into consideration, which is rarely discussed in the previous work.

Clinical and Molecular Characteristics of 60 Patients With Human Immunodeficiency Virus-Negative Castleman Disease.

Castleman disease (CD) is a rare lymphoproliferative disorder. The mechanistic target of rapamycin (mTOR) pathway is a key regulator of various cellular functions, which may be related with the potential mechanisms of CD occurrence. We retrospectively collected the clinical information of 60 CD patients diagnosed in the First Affiliated Hospital of Zhengzhou University. And FFPE biopsy specimens were collected from 31 patients (12 unicentric CD patients and 19 multicentric CD patients) to detect the mTOR pathway protein expression. We are the first to demonstrate that thrombocytopenia and hypoalbuminemia are independent poor prognostic factors for CD. Moreover, mTOR activation was higher in CD compared to reactive lymphoid hyperplasia (used as a control group). This study offers some elucidation for the management and treatment of CD patients.

The prognostic nutritional index, an independent predictor of overall survival for newly diagnosed follicular lymphoma in China.

Objective: The prognostic nutritional index (PNI) is an important prognostic factor for survival outcomes in various hematological malignancies. The current study focused on exploring the predictive value of the PNI in newly diagnosed follicular lymphoma (FL) in China. Materials and methods: The clinical indicators and follow-up data of 176 patients who received chemotherapy or immunotherapy combined with chemotherapy with FL in our hospital from January 2016 to March 2022 were retrospectively analyzed. Cox proportional hazard model was used for univariate and multivariate analyses. Kaplan-Meier curves were used to calculate survival rates and draw survival curves. The log-rank test was applied to compare differences between groups. Results: The optimal cut-off value of PNI was 44.3. All patients were divided into a high PNI group (>44.3) and a low PNI group (≤44.3). The low PNI group had a low CR rate and a high risk of death, with a tendency toward POD24, and Both OS and PFS were worse than those in the high PNI group. PNI was able to predict OS and PFS in FL patients and was the only independent predictor of OS (P = 0.014 HR 5.024; 95%CI 1.388∼18.178) in multivariate analysis. PNI could re-stratify patients into groups of high FLIPI score, high FLIPI2 score, no POD24, and rituximab combined with chemotherapy. Moreover, integrating PNI into the FLIPI and FLIPI2 models improved the area under the curve (AUC) for more accurate survival prediction and prognosis. Conclusion: PNI is a significant prognostic indicator for newly diagnosed FL in China that can early identify patients with poor prognosis and guide clinical treatment decisions.

Efficacy and Safety of a Pegasparaginase-Based Chemotherapy Regimen vs an L-asparaginase-Based Chemotherapy Regimen for Newly Diagnosed Advanced Extranodal Natural Killer/T-Cell Lymphoma: A Randomized Clinical Trial.

Importance: The L-asparaginase-based SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen has shown higher response rates and survival benefit over an anthracycline-containing regimen. However, the safety profile was not satisfied. A well-tolerated regimen with promising efficacy is lacking. Objective: To compare the efficacy and safety of the DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) regimen with the SMILE regimen in newly diagnosed advanced-stage (III/IV) extranodal natural killer/T-cell lymphoma (ENKL). Design, Setting, and Participants: This was an open-label, multicenter, randomized clinical trial that took place across 12 participating hospitals in China from January 2011 to February 2019. Patients were eligible if they were 14 to 70 years old with newly diagnosed ENKL in stages III/IV and had an Eastern Cooperative Oncology Group performance status of 0 to 2. Eligible patients were evenly randomized to either the DDGP or SMILE group. Interventions: Patients in each group were treated with the assigned regimen every 21 days for 6 cycles. Main Outcomes and Measures: The primary end point was progression-free survival (PFS), and secondary end points included overall response rate and overall survival (OS). The adverse events between the DDGP and SMILE groups were compared. Results: Among the 87 randomized patients, 80 received treatment (40 in the DDGP group and 40 in the SMILE group); the median (IQR) age was 43 (12) years, and 51 (64%) were male. The baseline characteristics were similar between the groups. At a median follow-up of 41.5 months, the median PFS was not reached in the DDGP group vs 6.8 months in the SMILE group (HR, 0.42; 95% CI, 0.23-0.77; P = .004), and the median OS was not reached in the DDGP group vs 75.2 months in the SMILE group (HR, 0.41; 95% CI, 0.19-0.89, P = .02). The PFS rate at 3 years and OS rate at 5 years were higher in the DDGP group vs the SMILE group (3-year PFS, 56.6% vs 41.8%; 5-year OS, 74.3% vs 51.7%). The overall response rate was higher in the DDGP group than in the SMILE group (90.0% vs 60.0%; P = .002). Grade 3 and 4 hematologic toxic effects were more frequently reported in the SMILE group vs the DDGP group (leukopenia, 85.0% vs 62.5%; neutropenia, 85.0% vs 65.0%). Conclusions and Relevance: In this randomized clinical trial, the DDGP regimen showed promising preliminary results for patients with newly diagnosed local advanced ENKL. A confirmation trial based on larger population is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01501149.

DDGP vs. SMILE in Relapsed/Refractory Extranodal Natural Killer/T-cell Lymphoma, Nasal Type: A Retrospective Study of 54 Patients.

Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a rare peripheral T-cell lymphoma that predominantly occurs in Asian and South American populations. The treatment of ENKL has been a challenge for a long time. This study was conducted to compare the clinical efficacy and safety of cisplatin, dexamethasone, gemcitabine, and pegaspargase (DDGP) and methotrexate, dexamethasone, ifosfamide, L-asparaginase, and etoposide (SMILE) regimens for relapsed/refractory ENKL and explore the prognostic factors. From October 2014 to July 2019, 54 patients with relapsed/refractory ENKL who received DDGP or SMILE chemotherapy were retrospectively assessed in this study. Thirty-one patients received DDGP chemotherapy and 23 patients received SMILE chemotherapy. A higher complete response rate was observed in patients treated with DDGP regimen (61.3% vs. 30.4%, P = 0.025). The DDGP group (95% confidence interval (CI) of 5-year progression-free survival (PFS): 24.6-66.2%; 95% CI of 5-year overall survival (OS): 8.5-91.7%) was also significantly associated with longer 5-year PFS and 5-year OS (P = 0.008 for 5-year PFS, P = 0.023 for 5-year OS). More serious leucopenia (P = 0.021), neutropenia (P = 0.041), and allergy (P = 0.040) were observed in the SMILE group. Post-treatment Epstein-Barr virus (EBV)-DNA status (P = 0.001 for PFS, P = 0.018 for OS) was identified as a significant prognostic factor for PFS and OS in multivariate analysis. The present research suggested that compared with SMILE chemotherapy, DDGP chemotherapy can significantly improve the response and survival of relapsed/refractory ENKL with better tolerance. Post-treatment EBV-DNA status was identified as a significant prognostic factor for PFS and OS in relapsed/refractory ENKL.

Combination of Decitabine and a Modified Regimen of Cisplatin, Cytarabine and Dexamethasone: A Potential Salvage Regimen for Relapsed or Refractory Diffuse Large B-Cell Lymphoma After Second-Line Treatment Failure.

OBJECTIVE: The prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R-DLBCL) after second-line treatment failure is extremely poor. This study prospectively observed the efficacy and safety of decitabine with a modified cisplatin, cytarabine, and dexamethasone (DHAP) regimen in R/R-DLBCL patients who failed second-line treatment. METHODS: Twenty-one R/R-DLBCL patients were enrolled and treated with decitabine and a modified DHAP regimen. The primary endpoints were overall response rate (ORR) and safety. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: ORR reached 50% (complete response rate, 35%), five patients (25%) had stable disease (SD) with disease control rate (DCR) of 75%. Subgroup analysis revealed patients over fifty years old had a higher complete response rate compared to younger patients (P = 0.005), and relapsed patients had a better complete response rate than refractory patients (P = 0.031). Median PFS was 7 months (95% confidence interval, 5.1-8.9 months). Median OS was not achieved. One-year OS was 59.0% (95% CI, 35.5%-82.5%), and two-year OS was 51.6% (95% confidence interval, 26.9%-76.3%). The main adverse events (AEs) were grade 3/4 hematologic toxicities such as neutropenia (90%), anemia (50%), and thrombocytopenia (70%). Other main non-hematologic AEs were grade 1/2 nausea/vomiting (40%) and infection (50%). No renal toxicity or treatment-related death occurred. CONCLUSION: Decitabine with a modified DHAP regimen can improve the treatment response and prognosis of R/R-DLBCL patients with good tolerance to AEs, suggesting this regimen has potential as a possible new treatment option for R/R-DLBCL patients after second-line treatment failure. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT03579082.

Fotemustine-based therapy in combination with rituximab as a first-line induction chemotherapy followed by WBRT for newly diagnosed primary central nervous system lymphoma: a prospective phase II trial.

OBJECTIVE: This study aimed to evaluate the safety, efficacy, and feasibility of the rituximab, fotemustine, pemetrexed, and dexamethasone (R-FPD) regimen followed by whole-brain radiotherapy (WBRT) for patients with primary central nervous system lymphoma (PCNSL). METHODS: A prospective, single-center phase II clinical trial was conducted. Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied. The R-FPD regimen consisted of rituximab (375 mg/m2 i.v. on D0), fotemustine (100 mg/m2 i.v. on D1), pemetrexed (600 mg/m2 i.v. on D1), and dexamethasone (40 mg i.v. on D1-5). Patients 60 years or younger who showed a complete response (CR) were treated with 23.4 Gy of WBRT after the end of chemotherapy; those older than 60 years with CR were treated with a wait-and-see approach; and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy + local tumor field irradiation up to 45 Gy, regardless of age. RESULTS: A total of 30 patients were included. After 2 cycles, the objective response rate (ORR) was 96.5% (28/29, 1 CR, 27 PR, 0 SD, and 1 PD). After 4 cycles, the ORR was 73.1% (19/26, 11 CR, 8 PR, 4 SD, and 3 PD). After WBRT, the ORR was 90.9% (10/11, 7 CR, 3 PR, and 1 SD). The grade III and IV toxicity responses were mainly leukopenia (20.0%), thrombocytopenia (23.3%), and anemia (10.0%). CONCLUSIONS: Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes, providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.