The patients with multiple myeloma were infected with COVID-19 during autologous stem cell transplantation: case report and literature review.

This paper introduces two cases of multiple myeloma, COVID-19 infection during autologous stem cell transplantation, the treatment process, and different results of the two patients, which provides a reference for how to carry out ASCT safely during the COVID-19 normalization stage.

Increased coexpression of PD-L1 and IDO1 is associated with poor overall survival in patients with NK/T-cell lymphoma.

Immunotherapy with programmed cell death 1 ligand 1 (PD-L1) blockade was effective in patients with NK/T-cell lymphoma. In addition to PD-L1, indoleamine 2,3-dioxygenase-1 (IDO1) is one of the most promising immunotherapeutic targets. High proportions of PD-L1 and IDO1 proteins were observed by immunohistochemistry (IHC) from 230 newly diagnosed patients with NK/T lymphoma with tissue samples from three cancer centers and were associated with poor overall survival (OS) in patients with NK/T lymphoma. Importantly, the coexpression of PD-L1 and IDO1 was related to poor OS and short restricted mean survival time in patients with NK/T lymphoma and was an independent prognostic factor in the training cohorts, and which was also validated in 58 NK/T lymphoma patients (GSE90597). Moreover, a nomogram model constructed with PD-L1 and IDO1 expression together with age could provide concise and precise predictions of OS rates and median survival time. The high-risk group in the nomogram model had a positive correlation with CD4 + T-cell infiltration in the validation cohort, as did the immunosuppressive factor level. Therefore, high PD-L1 and IDO1 expression was associated with poor OS in patients with NK/T lymphoma. PD-L1 and IDO1 might be potential targets for future immune checkpoint blockade (ICB) therapy for NK/T lymphoma.

High-dose methotrexate, thiotepa, orelabrutinib combined with or without rituximab in primary or secondary central nervous system diffuse large B-cell lymphoma: a single-center retrospective analysis.

Purpose: Central nervous system lymphoma (CNSL) is an aggressive non-Hodgkin's lymphoma (NHL) confined to the central nervous system (CNS). Orelabrutinib is an oral second-generation Bruton tyrosine kinase (BTK) inhibitor and a novel therapeutic strategy for CNSL. The purpose of this study was to evaluate the effectiveness and safety of high-dose methotrexate (HD-MTX), thiotepa, and orelabrutinib combined with or without rituximab (MTO±R)regimen in the treatment of patients with CNSL. Methods: A total of 14 patients with CNS diffuse large B-cell lymphoma (DLBCL) were included in this retrospective study. All patients received the regimen MTO±R. Overall response rate (ORR), complete response rate(CR), partial response (PR), stable disease (SD), progressive disease (PD), progression-free survival (PFS), overall survival (OS), and the safety of MTO±R were assessed by the investigator. Results: Fourteen patients were evaluable for safety, and 13 patients were evaluable for efficacy. The overall CR rate was 69.2%, and the ORR was 92.3% for total patients. For PCNSL, the CR rate and ORR were 55.6% and 88.9%, respectively. For relapsed/refractory CNSL, the CR rate and ORR were 66.7% and 91.7%, respectively. The median follow-up time was 12.8 months. The median PFS was 11.3 months, and the median OS was not achieved. The 12-month PFS and OS rates were 60% and 70%, respectively. Adverse events occurred in 17 cycles, and Grade 3 AEs occurred in 5 patients (35.7%). Conclusion: MTO±R was an efficacious and well-tolerated regimen in patients with CNSL. A novel BTK inhibitor in combination with chemotherapy offers a new potential therapeutic strategy for patients with CNSL.

Current status and future prospects of chimeric antigen receptor-T cell therapy in lymphoma research: A bibliometric analysis.

CAR-T cell therapy, a novel therapeutic approach that has attracted much attention in the field of cancer treatment at present, has become the subject of many studies and has shown great potential in the treatment of hematological malignancies, such as leukemia and lymphoma. This study aims to analyze the characteristics of articles published on CAR-T cell therapy in the lymphoma field and explore the existing hotspots and frontiers. The relevant articles published from 2013 to 2022 were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, Bibliometric online analysis platform, Microsoft Excel, and R software were used for bibliometric analysis and visualization. The number of publications related to the research has been increasing year by year, including 1023 articles and 760 reviews from 62 countries and regions, 2092 institutions, 1040 journals, and 8727 authors. The United States, China, and Germany are the main publishing countries in this research field. The top 10 institutions are all from the United States, the journal with the highest impact factor is BLOOD, the author with the most publications is Frederick L Locke, and the most influential author is Carl H June. The top three keywords are "Lymphoma," "Immunotherapy," and "Therapy." "Maude (2014)" is the most cited and strongest burstiness reference over the past decade. This study provides a comprehensive bibliometric analysis of CAR-T cell therapy in lymphoma, which can help researchers understand the current research hotspots in this field, explore potential research directions, and identify future development trends.

Arsenic trioxide-induced apoptosis contributes to suppression of viral reservoir in SIV-infected rhesus macaques.

Latent viral reservoir is recognized as the major obstacle to achieving a functional cure for HIV infection. We previously reported that arsenic trioxide (As2O3) combined with antiretroviral therapy (ART) can reactivate the viral reservoir and delay viral rebound after ART interruption in chronically simian immunodeficiency virus (SIV)-infected macaques. In this study, we further investigated the effect of As2O3 independent of ART in chronically SIV-infected macaques. We found that As2O3-only treatment significantly increased the CD4/CD8 ratio, improved SIV-specific T cell responses, and reactivated viral latency in chronically SIVmac239-infected macaques. RNA-sequencing analysis revealed that As2O3 treatment downregulated the expression levels of genes related to HIV entry and infection, while the expression levels of genes related to transcription initiation, cell apoptosis, and host restriction factors were significantly upregulated. Importantly, we found that As2O3 treatment specifically induced apoptosis of SIV-infected CD4+ T cells. These findings revealed that As2O3 might not only impact viral latency, but also induce the apoptosis of HIV-infected cells and thus block the secondary infection of bystanders. Moreover, we investigated the therapeutic potential of this regimen in acutely SIVmac239-infected macaques and found that As2O3 + ART treatment effectively restored the CD4+ T cell count, delayed disease progression, and improved survival in acutely SIV-infected macaques. In sum, this work provides new insights to develop As2O3 as a component of the "shock-and-kill" strategy toward HIV functional cure. IMPORTANCE Although antiretroviral therapy (ART) can effectively suppress the viral load of AIDS patients, it cannot functionally cure HIV infection due to the existence of HIV reservoir. Strategies toward HIV functional cure are still highly anticipated to ultimately end the pandemic of AIDS. Herein, we investigated the direct role of As2O3 independent of ART in chronically SIV-infected macaques and explored the underlying mechanisms of the potential of As2O3 in the treatment of HIV/SIV infection. Meanwhile, we investigated the therapeutic effects of ART+As2O3 in acutely SIVmac239-infected macaques. This study showed that As2O3 has the potential to be launched into the "shock-and-kill" strategy to suppress HIV/SIV reservoir due to its latency-reversing and apoptosis-inducing properties.

Treatment patterns and clinical outcomes of mantle cell lymphoma: A retrospective cohort study by CHOICE.

Regimens based on Bruton's tyrosine kinase inhibitors (BTKi) have been increasingly used to treat mantle cell lymphoma (MCL). A real-world multicenter study was conducted to characterize treatment patterns and outcomes in patients with newly diagnosed MCL by Chinese Hematologist and Oncologist Innovation Cooperation of the Excellent (CHOICE). The final analysis included 1261 patients. Immunochemotherapy was the most common first-line treatment, including R-CHOP in 34%, cytarabine-containing regimens in 21% and BR in 3% of the patients. Eleven percent (n = 145) of the patients received BTKi-based frontline therapy. Seventeen percent of the patients received maintenance rituximab. Autologous hematopoietic stem cell transplantation (AHCT) was conducted in 12% of the younger (<65 years) patients. In younger patients, propensity score matching analysis did not show significant difference in 2-year progression-free survival and 5-year overall survival rate in patients receiving standard high-dose immunochemotherapy followed by AHCT than induction therapy with BTKi-based regimens without subsequent AHCT (72% vs 70%, P = .476 and 91% vs 84%, P = .255). In older patients, BTKi combined with bendamustine plus rituximab (BR) was associated with the lowest POD24 rate (17%) compared with BR and other BTKi-containing regimens. In patients with resolved hepatitis B at the baseline, HBV reactivation rate was 2.3% vs 5.3% in those receiving anti-HBV prophylaxis vs not; BTKi treatment was not associated with higher risk of HBV reactivation. In conclusion, non-HD-AraC chemotherapy combined with BTKi may be a viable therapeutic strategy for younger patients. Anti-HBV prophylaxis should be implemented in patients with resolved hepatitis B.

A conjoint analysis of bulk RNA-seq and single-nucleus RNA-seq for revealing the role of ferroptosis and iron metabolism in ALS.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive and selective degeneration of motor neurons in the motor cortex of brain and spinal cord. Ferroptosis is a newly discovered form of cell death and reported to mediate selective motor neuron death in the mouse model of ALS. The growing awareness of ferroptosis and iron metabolism dysfunction in ALS prompted us to investigate the expression pattern of ferroptosis and iron metabolism-related genes (FIRGs) in ALS. Here, we performed a conjoint analysis of bulk-RNA sequence and single-nucleus RNA sequence data using the datasets from Gene Expression Omnibus (GEO) to reveal the role of FIRGs in ALS, especially in selective motor neuron death of ALS. We first investigated the differentially expressed genes (DEGs) between ALS and non-neurological controls. Weighted gene co-expression network analysis constructed the gene co-expression network and identified three modules closely associated with ALS. Fifteen FIRGs was identified as target genes based on least absolute shrinkage and selection operator regression analysis as follows: ACSL4, ANO6, ATP6V0E1, B2M, CD44, CHMP5, CYBB, CYBRD1, HIF1A, MOSPD1, NCF2, SDCBP, STEAP2, TMEM14C, ULK1. These genes could differentiate ALS patients from non-neurological controls (p < 2.2e-16) and had a valid value in predicting and diagnosing ALS (AUC = 0.881 in primary dataset and AUC = 0.768 in validation dataset). Then we performed the functional enrichment analysis of DEGs between ALS cases, the most significantly influenced by target genes, and non-neurological controls. The result indicated that the most significantly influenced functions in ALS pathogenesis by these identified FIRGs are synapse pathways, calcium signaling pathway, cAMP signaling pathway, and phagosome and several immune pathways. At last, the analysis of single- nuclear seq found that CHMP5, one of the 15 FIRGs identified by bulk single-nucleus RNA-seq data, was expressed significantly higher in ALS than pathologically normal (PN), specifically in excitatory neuron populations with layer 2 and layer 3 markers (Ex L2_L3), layer 3 and layer 5 markers (Ex L3_L5). Taken together, our study indicates the positive correlation between FIRGs and ALS, presents potential markers for ALS diagnosis and provides new research directions of CHMP5 function in selective motor neuron death in ALS.

Booster vaccination is required to elicit and maintain COVID-19 vaccine-induced immunity in SIV-infected macaques.

ABSTRACTProlonged infection and possible evolution of SARS-CoV-2 in patients living with uncontrolled HIV-1 infection highlight the importance of an effective vaccination regimen, yet the immunogenicity of COVID-19 vaccines and predictive immune biomarkers have not been well investigated. Herein, we report that the magnitude and persistence of antibody and cell-mediated immunity (CMI) elicited by an Ad5-vectored COVID-19 vaccine are impaired in SIV-infected macaques with high viral loads (> 105 genome copies per ml plasma, SIVhi) but not in macaques with low viral loads (< 105, SIVlow). After a second vaccination, the immune responses are robustly enhanced in all uninfected and SIVlow macaques. These responses also show a moderate increase in 70% SIVhi macaques but decline sharply soon after. Further analysis reveals that decreased antibody and CMI responses are associated with reduced circulating follicular helper T cell (TFH) counts and aberrant CD4/CD8 ratios, respectively, indicating that dysregulation of CD4+ T cells by SIV infection impairs the COVID-19 vaccine-induced immunity. Ad5-vectored COVID-19 vaccine shows no impact on SIV loads or SIV-specific CMI responses. Our study underscores the necessity of frequent booster vaccinations in HIV-infected patients and provides indicative biomarkers for predicting vaccination effectiveness in these patients.

Global Research Trends on the Treatment of Diffuse Large B-Cell Lymphoma: A Bibliometric and Visualized Study.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype. Treatment of DLBCL has improved greatly in recent decades, with thousands of papers published. We conducted a bibliometric analysis of the literature on DLBCL treatment, and discussed cooperation among authors, countries, and institutions, and identified research hotspots for DLBCL treatment. We searched the Web of Science Core Collection (WOSCC) using "Diffuse Large B Cell Lymphoma or DLBCL" and "Treatment or Therapy or Clinical Trial" as the subject terms, and analyzed the publication year, research direction, country/region, institution, author, source publication, distribution of funding institutions, and other conditions provided by the database. In addition, scientometrics software was used to analyze literature citations and cooperative publications. Bibliometric analyses were performed using https://bibliometric.com/app and VOSviewer. Network maps were generated to evaluate collaborations between different authors, countries, institutions, and keywords. A total of 7,255 studies on treatment of DLBCL were retrieved from the WOSCC on February 19, 2021. We found that the number of publications increased gradually from 1999 to 2021, and this trend was relatively stable in the past 3 years. The countries that produced the most publications were the United States, China, and Japan. Among institutions, University of Texas MD Anderson Cancer Center published the most manuscripts. Furthermore, the United States also had the most annual publications, citations, distribution of journal sources, and funding. Cooperative research between countries is also relatively important to treatment of DLBCL. Therapeutic regimens such as CHOP and R-CHOP, and immunotherapy (CAR-T, PD1/PDL1, and CAR-NK, etc.), have received increased attention. Bibliometric analysis of studies related to DLBCL treatment can help researchers and clinical workers quickly understand the hotspots and development trends in this field, and provide reference for the formulation of public health policies.

Vaccine with bacterium-like particles displaying HIV-1 gp120 trimer elicits specific mucosal responses and neutralizing antibodies in rhesus macaques.

Preclinical studies have shown that the induction of secretory IgA (sIgA) in mucosa and neutralizing antibodies (NAbs) in sera is essential for designing vaccines that can effectively block the transmission of HIV-1. We previously showed that a vaccine consisting of bacterium-like particles (BLPs) displaying Protan-gp120AE-MTQ (PAM) could induce mucosal immune responses through intranasal (IN) immunization in mice and NAbs through intramuscular (IM) immunization in guinea pigs. Here, we evaluated the ability of this vaccine BLP-PAM to elicit HIV-1-specific mucosal and systemic immune responses through IN and IM immunization combination strategies in rhesus macaques. First, the morphology, antigenicity and epitope accessibility of the vaccine were analysed by transmission electron microscopy, bio-layer interferometry and ELISA. In BLP-PAM-immunized macaques, HIV-1-specific sIgA were rapidly induced through IN immunization in situ and distant mucosal sites, although the immune responses are relatively weak. Furthermore, the HIV-1-specific IgG and IgA antibody levels in mucosal secretions were enhanced and maintained, while production of serum NAbs against heterologous HIV-1 tier 1 and 2 pseudoviruses was elicited after IM boost. Additionally, situ mucosal responses and systemic T cell immune responses were improved by rAd2-gp120AE boost immunization via the IN and IM routes. These results suggested that BLP-based delivery in combination with the IN and IM immunization approach represents a potential vaccine strategy against HIV-1.

Successful Treatment of Primary CNS Extranodal NK/T-Cell Lymphoma with Surgery and Chemotherapy Combined with Sintilimab: A Case Report and Literature Review.

Primary central nervous system extranodal natural killer/T-cell lymphoma (PCNS ENK/TCL) is an extremely rare lymphoma. Only 23 cases of PCNS ENK/TCL have been reported in the English literature. Due to the rarity of this lymphoma, an effective therapeutic strategy has not been defined. Generally, this type of lymphoma is treated with surgery, intrathecal chemotherapy, and postoperative chemoradiation therapy. The prognosis is poor. Herein, we present a case of primary brain NK/T cell lymphoma in a 50-year-old immunocompetent Chinese female and review the literature. The patient underwent intracranial tumor resection and was subsequently treated with a PD1 monoclonal antibody (Sintilimab) combined with chemotherapy. The patient survived 15 months after diagnosis. This is the first report of PCNS ENK/TCL treated with surgery and chemotherapy combined with immunotherapy and suggests an effective treatment regimen for PCNS ENK/TCL.

Exacerbated AIDS Progression by PD-1 Blockade during Therapeutic Vaccination in Chronically Simian Immunodeficiency Virus-Infected Rhesus Macaques after Interruption of Antiretroviral Therapy.

The persistence of cells latently infected with HIV-1, named the latent reservoir, is the major barrier to HIV-1 eradication, and the formation and maintenance of the latent reservoir might be exacerbated by activation of the immunoinhibitory pathway and dysfunction of CD8+ T cells during HIV-1 infection. Our previous findings demonstrated that prophylactic vaccination combined with PD-1 blockade generated distinct immune response profiles and conferred effective control of highly pathogenic SIVmac239 infection in rhesus macaques. However, to our surprise, herein we found that a therapeutic vaccination in combination with PD-1 blockade resulted in activation of the viral reservoir, faster viral rebound after treatment interruption, accelerated AIDS progression, and, ultimately, death in chronically SIV-infected macaques after antiretroviral therapy (ART) interruption. Our study further demonstrated that the SIV provirus was preferentially enriched in PD-1+CD4+ T cells due to their susceptibility to viral entry, potent proliferative ability, and inability to perform viral transcription. In addition, the viral latency was effectively reactivated upon PD-1 blockade. Together, these results suggest that PD-1 blockade may be a double-edged sword for HIV-1 immunotherapy and provide important insight toward the rational design of immunotherapy strategies for an HIV-1 cure. IMPORTANCE As it is one of the most challenging public health problems, there are no clinically effective cure strategies against HIV-1 infection. We demonstrated that prophylactic vaccination combined with PD-1 blockade generated distinct immune response profiles and conferred better control of highly pathogenic SIVmac239 infection in rhesus macaques. In the present study, to our surprise, PD-1 blockade during therapeutic vaccination accelerated the reactivation of latent reservoir and AIDS progression in chronically SIV-infected macaques after ART interruption. Our study further demonstrated that the latent SIV provirus was preferentially enriched in PD-1+CD4+ T cells because of its susceptibility to viral entry, inhibition of SIV transcription, and potent ability of proliferation, and the viral latency was effectively reactivated by PD-1 blockade. Therefore, PD-1 blockade might be a double-edged sword for AIDS therapy. These findings provoke interest in further exploring novel treatments against HIV-1 infection and other emerging infectious diseases.

Survival Analysis of Hepatosplenic T Cell Lymphoma: A Population-Based Study Using SEER.

PURPOSE: Hepatosplenic T cell lymphoma (HSTCL) is a rare tumor that lacks data to guide management decisions. To shed light on the nature and therapy of the entity, we conducted this study. PATIENTS AND METHODS: We retrospectively reviewed patients diagnosed with HSTCL between 1975 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database to analyze the clinical characteristics and survival outcome compared with PTCL-NOS and ALK+ ALCL. RESULTS: A total of 123 HSTCLs were included in the analysis. Most patients were aged ≤60 years (81.3%) and had a male predominance (69.1%). Organs with lymphoma infiltration of HSTCL were more common in the spleen (98.4%). The 1-year, 3-year, and 5-year overall survival (OS) rates in the entire HSTCL cohort were 56.9% (95% CI, 47.5-66.3%), 37.6% (95% CI, 28.0-47.2%), and 31.6.0% (95% CI, 22.2-41.0%), respectively. The overall survival (OS) of HSTCL patients was similar to that of PTCL-NOS patients (P = 0.128) but worse than that of patients with ALK+ ALCL (P < 0.001). The disease-specific survival (DSS) of HSTCL patients was worse than that of PTCL-NOS and ALK+ ALCL patients (P < 0.05). The same tendency was found in the matched data set. Cox regression analyses indicated that the use of chemotherapy combined with topical treatment may improve the survival of patients with HSTCL. CONCLUSION: A higher proportion of young patients and a strong male predominance were found in HSTCL. Chemotherapy combined with topical treatment may be an optional regimen. Further studies are needed to intensify efforts in dealing with this rare but unfavorable disease.

Ferroptosis-Related Gene Signature: A New Method for Personalized Risk Assessment in Patients with Diffuse Large B-Cell Lymphoma.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease, which makes prognostic prediction challenging. The rapid development of research on ferroptosis provides the possibility of its use in prognosis in cancer patients. The aim of the current investigation was to perform a systematic study of ferroptosis and DLBCL prognosis to identify prognostic biomarkers in DLBCL. MATERIALS AND METHODS: A total of 884 DLBCL patients from the Gene Expression Omnibus database were included in this study and were divided into a training set and a validation set. Univariate Cox regression analysis was used to investigate relationships between gene expression and prognostic values. Ferroptosis-related genes associated with overall survival in the training set were then extracted, and the least absolute shrinkage and selection operator Cox regression model was used to establish an eight-gene signature, comprising ZEB1, PSAT1, NGB, NFE2L2, LAMP2, HIF1A, FH, and CXCL2. RESULTS: The signature exhibited significant independent prognostic value in both the training set and the validation set. It also exhibited strong prognostic value in subgroup analysis. A nomogram integrating the eight-gene signature and components of the International Prognostic Index facilitated reliable prognostic prediction. CONCLUSION: A novel and reliable ferroptosis-related gene signature that can effectively classify DLBCL patients into high-risk and low-risk groups in terms of survival rate was developed. It could be used for prognostic prediction in DLBCL patients. Targeting ferroptosis may be a therapeutic alternative in DLBCL.

Modulation of Antiviral Immunity and Therapeutic Efficacy by 25-Hydroxycholesterol in Chronically SIV-Infected, ART-Treated Rhesus Macaques.

Cholesterol-25-hydroxylase (CH25H) and its enzymatic product 25-hydroxycholesterol (25HC) exert broadly antiviral activity including inhibiting HIV-1 infection. However, their antiviral immunity and therapeutic efficacy in a nonhuman primate model are unknown. Here, we report that the regimen of 25HC combined with antiretroviral therapy (ART), provides profound immunological modulation towards inhibiting viral replication in chronically SIVmac239-infected rhesus macaques (RMs). Compared to the ART alone, this regimen more effectively controlled SIV replication, enhanced SIV-specific cellular immune responses, restored the ratio of CD4/CD8 cells, reversed the hyperactivation state of CD4+ T cells, and inhibited the secretion of proinflammatory cytokines by CD4+ and CD8+ T lymphocytes in chronically SIV-infected RMs. Furthermore, the in vivo safety and the preliminary pharmacokinetics of the 25HC compound were assessed in this RM model. Taken together, these assessments help explain the profound relationship between cholesterol metabolism, immune modulation, and antiviral activities by 25HC. These results provide insight for developing novel therapeutic drug candidates against HIV-1 infection and other related diseases.

Primary Mediastinal B-Cell Lymphoma: Novel Precision Therapies and Future Directions.

Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinicopathologic disease from other types of diffuse large B-cell lymphoma (DLBCL) with unique prognostic features and limited availability of clinical data. The current standard treatment for newly diagnosed PMBCL has long been dependent on a dose-intensive, dose-adjusted multi-agent chemotherapy regimen of rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH). Recent randomized trials have provided evidence that R-CHOP followed by consolidation radiotherapy (RT) is a valuable alternative option to first-line treatment. For recurrent/refractory PMBCL (rrPMBCL), new drugs such as pembrolizumab and CAR-T cell therapy have proven to be effective in a few studies. Positron emission tomography-computed tomography (PET-CT) is the preferred imaging modality of choice for the initial phase of lymphoma treatment and to assess response to treatment. In the future, baseline quantitative PET-CT can be used to predict prognosis in PMBCL. This review focuses on the pathology of PMBCL, underlying molecular basis, treatment options, radiotherapy, targeted therapies, and the potential role of PET-CT to guide treatment choices in this disease.

Identification of an individualized RNA binding protein-based prognostic signature for diffuse large B-cell lymphoma.

RNA binding proteins (RBPs) are increasingly appreciated as being essential for normal hematopoiesis and have a critical role in the progression of hematological malignancies. However, their functional consequences and clinical significance in diffuse large B-cell lymphoma (DLBCL) remain unknown. Here, we conducted a systematic analysis to identify RBP-related genes affecting DLBCL prognosis based on the Gene Expression Omnibus database. By univariate and multivariate Cox proportional hazards regression (CPHR) methods, six RBPs-related genes (CMSS1, MAEL, THOC5, PSIP1, SNIP1, and ZCCHC7) were identified closely related to the overall survival (OS) of DLBCL patients. The RBPs signature could efficiently distinguished low-risk from high-risk patients and could serve as an independent and reliable factor for predicting OS. Moreover, Gene Set Enrichment Analysis revealed 17 significantly enriched pathways between high- versus low-risk group, including the regulation of autophagy, chronic myeloid leukemia, NOTCH signaling pathway, and B cell receptor signaling pathway. Then we developed an RBP-based nomogram combining other clinical risk factors. The receiver operating characteristic curve analysis demonstrated high prognostic predictive efficiency of this model with the area under the curve values were 0.820 and 0.780, respectively, in the primary set and entire set. In summary, our RBP-based model could be a novel prognostic predictor and had the potential for developing treatment targets for DLBCL.

Identification and Validation of a Prognostic Gene Signature for Diffuse Large B-Cell Lymphoma Based on Tumor Microenvironment-Related Genes.

Diffuse large B-cell lymphoma (DLBCL) is an extremely heterogeneous tumor entity, which makes prognostic prediction challenging. The tumor microenvironment (TME) has a crucial role in fostering and restraining tumor development. Consequently, we performed a systematic investigation of the TME and genetic factors associated with DLBCL to identify prognostic biomarkers for DLBCL. Data for a total of 1,084 DLBCL patients from the Gene Expression Omnibus database were included in this study, and patients were divided into a training group, an internal validation group, and two external validation groups. We calculated the abundance of immune-stromal components of DLBCL and found that they were related to tumor prognosis and progression. Then, differentially expressed genes were obtained based on immune and stromal scores, and prognostic TME-related genes were further identified using a protein-protein interaction network and univariate Cox regression analysis. These genes were analyzed by the least absolute shrinkage and selection operator Cox regression model to establish a seven-gene signature, comprising TIMP2, QKI, LCP2, LAMP2, ITGAM, CSF3R, and AAK1. The signature was shown to have critical prognostic value in the training and validation sets and was also confirmed to be an independent prognostic factor. Subgroup analysis also indicated the robust prognostic ability of the signature. A nomogram integrating the seven-gene signature and components of the International Prognostic Index was shown to have value for prognostic prediction. Gene set enrichment analysis between risk groups demonstrated that immune-related pathways were enriched in the low-risk group. In conclusion, a novel and reliable TME relevant gene signature was proposed and shown to be capable of predicting the survival of DLBCL patients at high risk of poor survival.

Optimal Courses of Chemotherapy Combined with Radiotherapy for Low-Risk Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Propensity Score Matching Analysis.

PURPOSE: This retrospective study compared effectiveness between ≤4 cycles and ≥5 cycles of L-asparaginase/pegaspargase-based chemoradiation in newly diagnosed low-risk extranodal natural killer/T-cell lymphoma (ENKTL), nasal type classified according to the Prognostic Index of Natural Killer (PINK) lymphoma model. PATIENTS AND METHODS: Patients were categorized into ≤4-cycle (2-4 chemotherapy cycles, n = 166) and ≥5-cycle groups (5-6 cycles, n = 86). Propensity score matching analysis was used to reduce potential confounding bias between the two groups. Treatment responses, adverse events, and survival outcomes between the two groups were analyzed. RESULTS: No matter before or after matching (65 in the ≤4-cycle group, 65 in the ≥5-cycle group), response rates and survival outcomes were similar between the ≤4-cycle and ≥5-cycle groups. Incidences of grade 1-2 anemia and transaminase elevation were higher in the ≥5-cycle group. After matching, for stage IE disease, there were no differences in response rates and survival outcomes between the two groups. For stage IIE disease, the complete response rate was higher in the ≥5-cycle group (72.4% vs 92.6%, p = 0.049), and the 3-year overall survival (65.5% vs 85.2%, p = 0.024) and 3-year progression-free survival (58.6% vs 81.5%, p = 0.027) rates were significantly extended in the ≥5-cycle group. CONCLUSION: When chemoradiotherapy strategies with L-asparaginase/pegaspargase-based regimens are applied to modern low-risk ENKTL patients classified according to the PINK model, it may be better to moderately extend chemotherapy courses in patients with stage IIE disease.