Sintilimab (anti-PD-1 antibody) plus chidamide (histone deacetylase inhibitor) in relapsed or refractory extranodal natural killer T-cell lymphoma (SCENT): a phase Ib/II study.

Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%. Patients received escalating doses of chidamide, administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months. No dose-limiting events were observed, RP2D of chidamide was 30 mg twice a week. Twenty-nine patients were enrolled in phase 2. In the intention-to-treat population (n = 37), overall response rate was 59.5% with a complete remission rate of 48.6%. The median DOR, progression-free survival (PFS), and overall survival (OS) were 25.3, 23.2, and 32.9 months, respectively. The most common grade 3 or higher treatment-emergent adverse events (AEs) were neutropenia (28.9%) and thrombocytopenia (10.5%), immune-related AEs were reported in 18 (47.3%) patients. Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role. STAT3 mutation shows an unfavorable prognosis. Although outcome of anticipate ORR was not achieved, sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time. It is a promising therapeutic option for this population.

Extranodal NK/T-Cell Lymphoma Predominantly Composed of Anaplastic Cells: A Frequently Misdiagnosed and Highly Aggressive Variant.

Extranodal NK/T-cell lymphoma (ENKTL) is a non-Hodgkin lymphoma associated with the Epstein-Barr virus that primarily affects individuals in East Asia and indigenous populations in Central and South America. Morphologically, ENKTL typically consists of medium-sized cells or a combination of small and large cells. This report presents 10 cases characterized by predominantly anaplastic cells with diffuse expression of CD30, resembling anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK-negative ALCL) and demonstrating highly aggressive behavior. The cohort included 9 males and 1 female, ranging in age from 29 to 65 years (median age: 47 y). Eight patients presented with nasal disease, while 2 had non-nasal disease. Five patients had stage I/II disease, and the remaining 5 had stage III/IV disease. Morphologically, necrosis was observed in 9 cases, angiocentric-angiodestructive growth in 3 cases, and pseudoepitheliomatous hyperplasia in 2 cases. Anaplastic cells predominated in all cases, with some displaying eccentric, horseshoe-shaped, or kidney-shaped nuclei (referred to as "Hallmark" cells). The morphology profile was monomorphic in 3 cases and polymorphic in 7 cases. Immunohistochemically, all cases tested positive for cytotoxic granule markers (TIA1 and granzymeB) and Epstein-Barr virus-encoded RNA. Cytoplasmic expression of CD3ε and CD56 was observed in 9 of 10 cases. Interestingly, most cases (7 of 8) exhibited variable expression of MuM1, ranging from 10% to 90%. All cases showed diffuse positivity for CD30 but were negative for ALK, resulting in 3 cases being initially misdiagnosed as ALK-negative ALCL. Compared with nonanaplastic cases, anaplastic cells predominant ENKTL had a significantly higher frequency of "B" symptoms, bone marrow involvement, hemophagocytic lymphohistiocytosis, and higher Ki67 proliferative index. These findings provide valuable information for pathologists, expanding their understanding of the cytologic spectrum of ENKTL. This rare variant of ENKTL, characterized by the predominance of anaplastic cells and diffuse CD30 expression, exhibits high aggressiveness and should be differentiated from ALK-negative ALCL. Awareness of this uncommon variant is crucial in preventing misdiagnosis and ensuring the timely initiation of therapy.

PD-1 blockade combined with ICE regimen in relapsed/refractory diffuse large B-cell lymphoma.

The prognosis of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. The efficacy of salvage therapy with ICE (ifosfamide, carboplatin, and etoposide) is limited. DLBCL can evade immune surveillance by upregulating programmed cell death ligand 1 (PD-L1). The purpose of this study was to explore the efficacy and safety of programmed cell death 1 (PD-1) blockade combined with ICE regimen (P-ICE) in the treatment of R/R DLBCL patients. In this study, we retrospectively explored efficacy and toxicity in R/R DLBCL patients treated with P-ICE. Prognostic biomarkers, including clinical features and molecular markers related to efficacy, were explored. From February 2019 to May 2020, a total of 67 patients treated with the P-ICE regimen were analyzed. The median follow-up time was 24.7 months (range: 1.4-39.6 months), with an objective response rate (ORR) of 62.7% and a complete response rate (CRR) of 43.3%. The 2-year progression-free survival (PFS) and overall survival (OS) rates were 41.1% (95% CI: 35.0-47.2%) and 65.6% (95% CI: 59.5-71.7%), respectively. Age, Ann Arbor stage, international prognostic index (IPI) score, and response to first-line chemotherapy were correlated with the ORR. Grade 3 and 4 adverse events (AEs) related to the P-ICE regimen were reported in 21.5% of patients. The most common AE was thrombocytopenia (9.0%). No treatment-related deaths occurred. In patients with R/R DLBCL, the P-ICE regimen has promising efficacy and mild toxicity.

Galectin-9 Facilitates Epstein-Barr Virus Latent Infection and Lymphomagenesis in Human B Cells.

The immune regulator galectin-9 (Gal-9) is commonly involved in the regulation of cell proliferation, but with various impacts depending on the cell type. Here, we revealed that Gal-9 expression was persistently increased in Epstein-Barr virus (EBV)-infected primary B cells from the stage of early infection to the stage of mature lymphoblastoid cell lines (LCLs). This sustained upregulation paralleled that of gene sets related to cell proliferation, such as oxidative phosphorylation, cell cycle activation, and DNA replication. Knocking down or blocking Gal-9 expression obstructed the establishment of latent infection and outgrowth of EBV-infected B cells, while exogenous Gal-9 protein promoted EBV acute and latent infection and outgrowth of EBV-infected B cells at the early infection stage. Mechanically, stimulator of interferon gene (STING) activation or signal transducer and activator of transcription 3 (STAT3) inhibition impeded the outgrowth of EBV-infected B cells and promotion of Gal-9-induced lymphoblastoid cell line (LCL) transformation. Accordingly, Gal-9 expression was upregulated by forced EBV nuclear antigen 1 (EBNA1) expression in 293T cells in vitro. Clinical data showed that Gal-9 expression in B-cell lymphomas (BCLs) correlated positively with EBNA1 and disease stage. Targeting Gal-9 slowed LCL tumor growth and metastasis in xenografted immunodeficient mice. These findings highlight an oncogenic role of Gal-9 in EBV-associated BCLs, indicating that Gal-9 boosts the transformation of EBV-infected B cells. IMPORTANCE The cross talk between Epstein-Barr virus (EBV) and the host cell transcriptome assumes important roles in the oncogenesis of EBV-associated malignancies. Here, we first observed that endogenous Gal-9 expression was persistently increased along with an overturned V-type change in antivirus signaling during the immortalization of EBV-transformed B cells. Upregulation of Gal-9 promoted the outgrowth and latent infection of EBV-infected B cells, which was linked to B-cell-origin tumors by suppressing STING signaling and subsequently promoting STAT3 phosphorylation. EBV nuclear antigen EBNA1 induced Gal-9 expression and formed a positive feedback loop with Gal-9 in EBV-infected B cells. Tumor Gal-9 levels were positively correlated with disease stage and EBNA1 expression in patients with B-cell lymphomas (BCLs). Targeting Gal-9 slowed the growth and metastases of LCL tumors in immunodeficient mice. Altogether, our findings indicate that Gal-9 is involved in the lymphomagenesis of EBV-positive BCLs through cross talk with EBNA1 and STING signals.

The emerging role of anti-PD-1 antibody-based regimens in the treatment of extranodal NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis.

PURPOSE: Anti-PD-1 antibody (anti-PD-1 mAb) showed favorable outcomes in some patients with relapsed/refractory (r/r) extranodal NK/T-cell lymphoma (ENKTL). However, the role of anti-PD-1 antibody in NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis (NK/T-LAHS) remains unclear. Here, we evaluated the efficacy and toxicity of anti-PD-1 antibody-based treatment in NK/T-LAHS patients. METHODS: The clinical data of 98 patients diagnosed with NK/T-LAHS at Sun Yat-sen University Cancer Center and the First Affiliated Hospital of Guangdong Pharmaceutical University from May 2014 to November 2021 were retrospectively analyzed. All patients received anti-HLH [HLH-2004 (etoposide, dexamethasone, cyclosporine A) or DEP-based (liposomal doxorubicin, etoposide, methylprednisolone)] regimen and sequential anti-ENKTL chemotherapy (ChT) combined with anti-PD-1 antibody or not. RESULTS: The overall response rate (ORR) of the anti-PD-1 mAb plus ChT regimens was higher than that of the ChT regimens (73.3% vs. 45.5%, P = 0.041). The toxicity of the anti-PD-1 mAb plus ChT regimens was tolerable. Except for higher rate of neutropenia, no significant difference in adverse events (AEs) was observed between the two groups. When the optimal response to anti-ENKTL was achieved, the median EBV DNA levels in patients who received anti-PD-1 mAb plus ChT were significantly lower than patients who received ChT only (878 copies/mL vs. 18,600 copies/mL, P = 0.001). With a median follow-up of 26.6 months (range 0-65.9 months), the median overall survival (mOS) was 3.5 months (95% CI：2.3-4.7 months). Patients treated with anti-PD-1 mAb plus ChT experienced a longer mOS than those who received ChT only [5.2 months (95% CI: 2.5-7.8 months) vs. 1.5 months (95% CI: 0.5-2.6 months), P = 0.002]. Cox multivariate analysis found that anti-PD-1 mAb was an independent prognostic factor for all NK/T-LAHS patients. CONCLUSION: In conclusion, anti-PD-1 mAb combined with ChT regimens seemed to be associated with prolonged survival in NK/T-LAHS patients and may represent a potentially promising treatment strategy for this population.

Immunogenic Cell Death (ICD)-Related Gene Signature Could Predict the Prognosis of Patients with Diffuse Large B-Cell Lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent type of lymphoma that is potentially curable by chemotherapy. Immunogenic cell death (ICD) is regarded as an essential process for the clearance of residual tumor cells. However, the impact of ICD on DLBCL remains unknown. Here, we tried to explore the prognostic role of ICD in DLBCL. METHODS: A gene expression microarray of DLBCL was downloaded from the Gene Expression Omnibus (GEO). The genes involved in ICD were obtained via literature reviews. Then, based on univariate, multivariate, and LASSO Cox regression analysis, the ICD-related gene signature was identified. The effect of the ICD-related gene signature on DLBCL was explored. The chi-square test was used to compare complete response rate (CRR) and recurrence rate between high- and low-risk groups. RESULTS: The signature based on 12 ICD-related genes could independently predict the overall survival of DLBCL. Furthermore, high risk was linked to lower CRR and higher recurrence rate. Then, a nomogram based on the ICD-related gene signature was established. The area under the curve of the prediction model reached 0.820 in the training set and 0.780 in the validation set. CONCLUSIONS: This study suggested that the ICD-related gene signature could be a novel prognostic indicator for DLCBL.

Systematic Oxidative Stress Indexes Associated with the Prognosis in Patients with T Lymphoblastic Lymphoma/Leukemia.

Background: T lymphoblastic lymphoma/leukemia (T-LBL/ALL) is an aggressive malignant tumor with 5-year overall survival (OS) rate reached 80% after high-dose chemotherapy. Due to the relatively low incidence of T-LBL/ALL, only a few risk factors have been identified. The occurrence and prognosis of malignant tumors are closely related to oxidative stress, but the prognostic relationship between T-LBL/ALL and systematic oxidative stress indexes has not been reported yet. Methods: A total of 258 T-LBL/ALL patients were retrospectively analyzed. The relationship between systematic oxidative stress indexes, such as creatinine (CRE), gamma-glutamyl transpeptidase (γ-GGT), albumin (ALB), alkaline phosphatase (ALP), fibrinogen (FBG), C-reactive protein (CRP) and total bilirubin (TBIL), and survival of T-LBL/ALL patients, was analyzed. The weight of indexes was used to calculate the patients' oxidative stress risk score. The independent prognostic value of oxidative stress risk grouping (OSRG) was analyzed. Results: Higher CRE, CRP, and lower ALB were associated with poorer OS in T-LBL/ALL patients. The OSRG established by CRE, ALB, and CRP was an independent prognostic factor for OS of T-LBL/ALL patients. Patients in the high-risk group were more likely to be patients older than 14 years old and patients with superior vena cava obstruction syndrome (SVCS), pleural effusion, pericardial effusion, and mediastinal mass. Conclusion: For OS in T-LBL/ALL patients, OSRG was observed as an independent prognostic factor, which provided a new idea for accurate prognostic prediction.

A Novel Systematic Oxidative Stress Score Predicts the Prognosis of Patients with Operable Breast Cancer.

BACKGROUND: Breast cancer was associated with imbalance between oxidation and antioxidation. Local oxidative stress in tumors is closely related to the occurrence and development of breast cancer. However, the relationship between systematic oxidative stress and breast cancer remains unclear. This study is aimed at exploring the prognostic value of systematic oxidative stress in patients with operable breast cancer. METHODS: A total of 1583 operable female breast cancer patients were randomly assigned into the training set and validation set. The relationship between systematic oxidative stress biomarkers and prognosis were analyzed in the training and validation sets. RESULTS: The systematic oxidative stress score (SOS) was established based on five systematic oxidative stress biomarkers including serum creatinine (CRE), serum albumin (ALB), total bilirubin (TBIL), lactate dehydrogenase (LDH), and blood urea nitrogen (BUN). SOS was an independent prognostic factor for operable breast cancer patients. A nomogram based on SOS and clinical characteristics could accurately predict the prognosis of operable breast cancer patients, and the area under the curve (AUC) of the nomogram was 0.823 in the training set and 0.872 in the validation set, which was much higher than the traditional prognostic indicators. CONCLUSIONS: SOS is an independent prognostic indicator for operable breast cancer patients. A prediction model based on SOS could accurately predict the outcome of operable breast cancer patients.

A Novel Pyroptosis-Associated Long Non-coding RNA Signature Predicts Prognosis and Tumor Immune Microenvironment of Patients With Breast Cancer.

Background: Pyroptosis, a kind of programmed cell death characterized by the rupture of cell membranes and the release of inflammatory substances, plays an important role in the occurrence and development of cancer. However, few studies focus on the pyroptosis-associated long non-coding RNAs (lncRNAs) in breast cancer (BC). The prognostic value of pyroptosis-associated lncRNAs and their relationship with tumor microenvironment (TME) in BC remain unclear. The purpose of this study was to explore the prognostic role of pyroptosis-associated lncRNAs and their relationship with TME in BC. Methods: The transcriptome data and clinical data of female BC patients were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 937 patients were randomly assigned to either training set or validation set. A pyroptosis-associated lncRNA signature was constructed in the training set and verified in the validation set. Functional analysis and immune microenvironment analysis related to pyroptosis-associated lncRNAs were performed. A nomogram based on the risk score and clinical characteristics was established. Results: A 9-pyroptosis-associated lncRNA signature was constructed to separate BC patients into two risk groups. High-risk patients had poorer prognosis than low-risk patients. The risk score was proven to be an independent prognostic factor by multivariate Cox regression analysis. Function analysis and immune microenvironment analysis showed that low-risk BC tended to be an immunologically "hot" tumor. A nomogram was constructed with risk score and clinical characteristics. Receiver operating characteristic curve (ROC) analysis demonstrated credible predictive power of the nomogram. The area under time-dependent ROC curve (AUC) reached 0.880 at 1 year, 0.804 at 3 years, and 0.769 at 5 years in the training set, and 0.799 at 1 year, 0.794 at 3 years, and 0.728 at 5 years in the validation set. Conclusion: We identified a novel pyroptosis-associated lncRNA signature that was an independent prognostic indicator for BC patients. Pyroptosis-associated lncRNAs had potential relationship with the immune microenvironment and might be therapeutic targets for BC patients.

The beneficial effect of Escalated-R-CHOP-21 for the treatment of diffuse large B-cell lymphoma in elderly male patients: A propensity-matched cohort study.

PURPOSE: Some studies have indicated that using 500 mg/m2 rituximab combined with CHOP-14 may be beneficial for elderly men but not women with diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to investigate the potential benefit of escalated doses of rituximab with CHOP-21 as the first-line treatment in male patients with DLBCL. METHODS: We performed a retrospective cohort study to analyze the survival benefit of rituximab 500 mg/m2 plus the CHOP-21 regimen (Escalated-R-CHOP-21) as the first-line treatment compared with using rituximab 375 mg/m2 plus the CHOP-21 regimen (Standard-R-CHOP-21) in men with DLBCL. We used propensity score matching to maximize the balance of the observed covariables. The primary endpoints of this study were the progression-free survival (PFS) rate and overall survival (OS) rate at 3 years. RESULTS: After a median follow-up of 47 months (IQR 31-65), no significant difference in PFS and OS was found for men treated with Escalated-R-CHOP-21 compared with Standard-R-CHOP-21 [3-year PFS: 69.7% versus 71.9%, p = 0.867; 3-year OS: 83.0% versus 82.4%, p = 0.660]. After 1:1 propensity score matching, we found that the patients using Escalated-R-CHOP-21 had statistically significant survival benefits relative to Standard-R-CHOP-21 among the 96 matched elderly male patients for 3-year PFS [75.5% (95% CI 62.8-88.2) versus 58.2% (95% CI 44.3-72.1); p = 0.019] and 3-year OS [86.6% (95% CI 76.4-96.8) versus 65.8% (95% CI 52.1-79.5); p = 0.017]. However, no differences in survival were observed for younger male patients. Furthermore, the dose effect in PFS of Escalated-R-CHOP-21 was more obvious for elderly male patients with no high-risk extranodal sites (p = 0.005 and interaction p = 0.030). CONCLUSION: Escalated-R-CHOP-21 could be a safe and effective option for treating elderly male patients with DLBCL. This study provides new insight into optimizing the standard treatment regimen, which may have important therapeutic implications in elderly male patients with DLBCL.

A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer.

Background: Ferroptosis, a regulated cell death which is driven by the iron-dependent peroxidation of lipids, plays an important role in cancer. However, studies about ferroptosis-related Long non-coding RNAs (lncRNAs) in breast cancer (BC) are limited. Besides, the prognostic role of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer remain unclear. This study aimed to explore the potential prognostic value of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer. Methods: RNA-sequencing data of female breast cancer patients were downloaded from TCGA database. 937 patients were randomly separated into training or validation cohort in 2:1 ratio. Ferroptosis-related lncRNAs were screened by Pearson correlation analysis with 239 reported ferroptosis-related genes. A ferroptosis-related lncRNAs signature was constructed with univariate and multivariate Cox regression analyses in the training cohort, and its prognostic value was further tested in the validation cohort. Results: An 8-ferroptosis-related-lncRNAs signature was developed by multivariate Cox regression analysis to divide patients into two risk groups. Patients in the high-risk group had worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed the risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The area under time-dependent ROC curve (AUC) reached 0.853 at 1 year, 0.802 at 2 years, 0.740 at 5 years in the training cohort and 0.791 at 1 year, 0.778 at 2 years, 0.722 at 5 years in the validation cohort. Further analysis demonstrated that immune-related pathways were significantly enriched in the high-risk group. Analysis of the immune cell infiltration landscape showed that breast cancer in the high-risk group tended be immunologically "cold". Conclusion: We identified a novel ferroptosis-related lncRNA signature which could precisely predict the prognosis of breast cancer patients. Ferroptosis-related lncRNAs may have a potential role in the process of anti-tumor immunity and serve as therapeutic targets for breast cancer.

A Systemic Inflammation Response Score for Prognostic Prediction of Breast Cancer Patients Undergoing Surgery.

Background: Systemic inflammatory response is related to the occurrence, progression, and prognosis of cancers. In this research, a novel systemic inflammation response score (SIRS) was calculated, and its prognostic value for postoperative stage I-III breast cancer (BC) patients was analyzed. Methods: 1583 BC patients were included in this research. Patients were randomly divided into a training cohort (n = 1187) and validation cohort (n = 396). SIRS was established in the training cohort based on independent prognostic hematological indicator, its relationship between prognosis and clinical features was analyzed. Then, a nomogram consisted of SIRS and clinical features was established, its performance was examined by calibration plots and receiver operating characteristic curve analysis. Results: The SIRS was an independent prognostic indicator for BC patients, and a high-SIRS was related to multifocality, advanced N stage, and worse prognosis. Incorporating SIRS into a nomogram could accurately predict the prognosis of BC patients, the results of receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of nomogram was up to 0.806 in training cohort and 0.905 in the validation cohort. Conclusion: SIRS was associated with the prognosis of patients with breast cancer. Nomogram based on SIRS can accurately predict the prognosis of breast cancer patients.

VISTA and PD-L1 synergistically predict poor prognosis in patients with extranodal natural killer/T-cell lymphoma.

Although PD-1/PD-L1 blockade therapy confers salutary effects across cancer types, their efficacy in Extranodal Natural killer/T-cell lymphoma (ENKTCL) patients is limited and unpredictable. Here, we comprehensively evaluated the expression profile of a panel of immune-regulatory makers to identify novel prognostic biomarkers and/or therapeutic targets for this malignancy. Using immunohistochemistry and multiplex immunofluorescence, we found that the expression of VISTA (88.1%) was predominantly in CD68+ macrophages and much higher than PD-L1 expression (68.7%) in ENKTCL. B7-H4 and HHLA2 proteins were not detected in ENKTCL. B7-H3 was expressed in minority of ENKTCL patients (13.7%) and mainly colocalized with CD31. A close correlation was detected between VISTA and PD-L1, but they were not co-expressed in the same cells. High expressions of VISTA or PD-L1 were significantly associated with detrimental clinicopathological characteristics, dismal prognosis, and high density of CD8+ TILs, and high VISTA expression was also significantly associated with high density of Foxp3+ TILs. VISTA combined with PD-L1 was an independent prognostic factor for PFS and OS. Moreover, the patients with high VISTA showed a poor response to PD-1 blockades in ENKTCL. In conclusion, these findings provide a rationale for VISTA as an ideal immunotherapeutic target next to PD-L1 for ENKTCL.

High IL-6 expression in the tumor microenvironment is associated with poor prognosis of patients with extranodal natural / killer T-cell lymphoma (ENKTL).

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.

Prior anti-PD-1 therapy as a risk factor for life-threatening peri-engraftment respiratory distress syndrome in patients undergoing autologous stem cell transplantation.

Peri-engraftment respiratory distress syndrome (PERDS) is a kind of potentially life-threatening complication of autologous stem cell transplantation (ASCT). PERDS is characterized by fever, dyspnea, and hypoxemia during neutrophil engraftment. In order to identify the high-risk factors for PERDS, we retrospectively analyzed 260 patients with lymphoma undergoing ASCT in recent five years. The conditioning regimen was BuCyE (busulfan, cyclophosphamide, and etoposide). There were 16 patients (6.1%) diagnosed as PERDS. In multivariate analysis, prior anti-programmed death-1 (PD-1) therapy (hazard ratio [HR] = 8.852, 95% confidence interval [CI]: 2.954-26.527, P < 0.001) and history of pulmonary disease (HR = 3.718, 95% CI: 1.197-11.545, P = 0.023) were independent risk factors for PERDS. Patients with prior anti-PD-1 therapy (n = 31) had higher incidence of engraftment syndrome (77.4% vs. 33.4%, P < 0.001), PERDS (25.8% vs. 3.5%, P < 0.001), and transplant-related mortality (9.7% vs. 0.4%, P < 0.001), compared with those without prior anti-PD-1 therapy (n = 229). Subgroup analysis showed that sintilimab seemed to be associated with higher incidence of PERDS (42.9% vs. 11.8%, P = 0.06) compared with non-sintilimab group (pembrolizumab or toripalimab). C-reactive protein might be a feasible early predictor for PERDS. In conclusion, our study suggests that prior anti-PD-1 therapy may be a strong risk factor for life-threatening PERDS in patients with lymphoma undergoing ASCT.

Identifying high-risk patients with natural killer/T-cell lymphoma undergoing autologous stem cell transplantation.

At present, autologous stem cell transplantation (ASCT) is considered as an optional consolidation therapy for natural killer/T-cell lymphoma (NKTCL). However, the high-risk patients undergoing ASCT are not clear enough. In this study, 56 patients with advanced staged or relapsed/refractory (R/R) NKTCL undergoing ASCT were reviewed. All patients achieved clinical complete response (CR) before ASCT. The median follow-up time was 36 months (range, 3-192 months). The three-year overall survival (OS) and three-year progression-free survival (PFS) were 70.2% and 56.5%, respectively. The independent prognostic factors for OS included prior testis involvement and pre-ASCT EBV-DNA. Patients without prior testis involvement and negative pre-ASCT EBV-DNA (group A) had better three-year OS (86.3% vs. 47.6%, p < .001) than the rest patients (group B). In conclusion, our study suggests that testis involvement and elevated EBV-DNA might be strong adverse prognostic factors for NKTCL. Patients without the above risk factors are more likely to benefit from ASCT.