Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

BACKGROUND: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear. METHODS: We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored. RESULTS: After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100). CONCLUSIONS: Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.).

Targeting the tumor microenvironment in primary central nervous system lymphoma: Implications for prognosis.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma, and there is limited research on its tumor microenvironment (TME). Nevertheless, more and more studies have evidence that TME has essential effects on tumor cell proliferation, immune escape, and drug resistance. Thus, it is critical to elucidate the role of TME in PCNSL. The understanding of the PCNSL TME is gradually unfolding, including factors that distinguish it from systemic diffuse large B-cell lymphoma (DLBCL). The TME in PCNSL exhibits both transcriptional and spatial intratumor heterogeneity. Cellular interactions between tumor cells and stroma cells reveal immune evasion signaling. The comparative analysis between PCNSL and DLBCL suggests that PCNSL is more likely to be an immunologically deficient tumor. In PCNSL, T cell exhaustion and downregulation of macrophage immune function are accompanied by suppressive microenvironmental factors such as M2 polarized macrophages, endothelin B receptor, HLA depletion, PD-L1, and TIM-3. MMP-9, Integrin-ß1, and ICAM-1/LFA-1 play crucial roles in transendothelial migration towards the CNS, while CXCL13/CXCR5, CD44, MAG, and IL-8 are essential for brain parenchymal invasion. Further, macrophages, YKL-40, CD31, CD105, PD-1/PD-L1 axis, osteopontin, galectin-3, aggregative perivascular tumor cells, and HLA deletion may contribute to poor outcomes in patients with PCNSL. This article reviews the effect of various components of TME on the progression and prognosis of PCNSL patients to identify novel therapeutic targets.

Challenges in the management of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma. Stereotactic biopsy remains the gold standard for the pathological diagnosis of PCNSL. However, certain new auxiliary diagnostic methods are considered to have good application prospects; these include cytokine and tumor circulating DNA, among others. Although new drugs such as immunomodulators, immune checkpoint inhibitors, chimeric antigen receptor T-cells, and Bruton tyrosine kinase inhibitors have brought hope owing to their improved efficacy, the high recurrence rate and subsequent high mortality remain barriers to long-term survival. Increasing emphasis is therefore being placed on consolidation treatments. Consolidation treatment strategies include whole brain radiotherapy, autologous hematopoietic stem cell transplantation, and non-myeloablative chemotherapy. As studies directly comparing the effectiveness and safety of different consolidation treatment schemes are lacking, the optimal consolidation strategy remains uncertain. This article will review the diagnosis and treatment of PCNSL, focusing on the progress in research pertaining to consolidation therapy.

Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace / 中西医结合学报

OBJECTIVE@#This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder (PTSD).@*METHODS@#The Web of Science database (2007-2022) was searched using the search terms "phytochemicals" and "PTSD," and relevant literature was compiled. Network clustering co-occurrence analysis and qualitative narrative review were conducted.@*RESULTS@#Three hundred and one articles were included in the analysis of published research, which has surged since 2015 with nearly half of all relevant articles coming from North America. The category is dominated by neuroscience and neurology, with two journals, Addictive Behaviors and Drug and Alcohol Dependence, publishing the greatest number of papers on these topics. Most studies focused on psychedelic intervention for PTSD. Three timelines show an "ebb and flow" phenomenon between "substance use/marijuana abuse" and "psychedelic medicine/medicinal cannabis." Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover, serotonin levels, and brain-derived neurotrophic factor expression.@*CONCLUSION@#Research on phytochemicals and PTSD is unevenly distributed across countries/regions, disciplines, and journals. Since 2015, the research paradigm shifted to constitute the mainstream of psychedelic research thus far, leading to the exploration of botanical active ingredients and molecular mechanisms. Other studies focus on anti-oxidative stress and anti-inflammation. Please cite this article as: Gao B, Qu YC, Cai MY, Zhang YY, Lu HT, Li HX, Tang YX, Shen H. Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace. J Integr Med. 2023; 21(4):385-396.

Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study.

Chimeric antigen receptor (CAR)-T cell therapy against T cell malignancies faces major challenges including fratricide between CAR-T cells and product contamination from the blasts. Allogeneic CAR-T cells, generated from healthy donor T cells, can provide ready-to-use, blast-free therapeutic products, but their application could be complicated by graft-versus-host disease (GvHD) and host rejection. Here we developed healthy donor-derived, CD7-targeting CAR-T cells (RD13-01) with genetic modifications to resist fratricide, GvHD and allogeneic rejection, as well as to potentiate antitumor function. A phase I clinical trial (NCT04538599) was conducted with twelve patients recruited (eleven with T cell leukemia/lymphoma, and one with CD7-expressing acute myeloid leukemia). All patients achieved pre-set end points and eleven proceeded to efficacy evaluation. No dose-limiting toxicity, GvHD, immune effector cell-associated neurotoxicity or severe cytokine release syndrome (grade ≥ 3) were observed. 28 days post infusion, 81.8% of patients (9/11) showed objective responses and the complete response rate was 63.6% (7/11, including the patient with AML). 3 of the responding patients were bridged to allogeneic hematopoietic stem cell transplantation. With a median follow-up of 10.5 months, 4 patients remained in complete remission. Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) reactivation was observed in several patients, and one died from EBV-associated diffuse large B-cell lymphoma (DLBCL). Expansion of CD7-negative normal T cells was detected post infusion. In summary, we present the first report of a Phase I clinical trial using healthy donor-derived CD7-targeting allogeneic CAR-T cells to treat CD7+ hematological malignancies. Our results demonstrated the encouraging safety and efficacy profiles of the RD13-01 allogeneic CAR-T cells for CD7+ tumors.

Non-Myeloablative Chemotherapy as Consolidation Strategy After High-Dose Methotrexate-Based Chemoimmunotherapy in Patients With Primary CNS Lymphoma: A Retrospective Single Center Study in China.

Primary central nervous system lymphoma (PCNSL) remains a disease with poor outcome and high recurrence rate. We retrospectively analyzed the clinical data of 243 immunocompetent patients with PCNSL in Beijing Tiantan Hospital. The median age of PCNSL patients was 57 years (range 10-95 years). For induction therapy, 94.7% of patients received high-dose methotrexate (HD-MTX) containing regimens, and 59.3% received rituximab, which increased over time. The overall response rate was 72.8%, with 58.8% achieving complete response. With a median follow-up of 27.0 months (95% confidence interval 23.6-30.4), the median progression-free survival (PFS) time was 14.0 months (95% CI 9.45-18.55), and the 2-year PFS rate was 33.2%. The median overall survival (OS) was not reached (NR), with an estimated overall survival rate at 4 years of 61.6%. Among 95 patients who completed sequential consolidation chemotherapy with either pemetrexed or etoposide plus cytarabine, the median PFS was 28 months (95% CI 17.11-38.89), and the estimated overall survival at 4 years was 78.7%. In conclusion, HD-MTX based induction chemotherapy with non-myeloablative sequential consolidation chemotherapy is an alternative feasible treatment option.

The PI3K/AKT/mTOR signaling pathway is aberrantly activated in primary central nervous system lymphoma and correlated with a poor prognosis.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a specific subtype of non-Hodgkin lymphoma that is highly invasive and confined to the central nervous system (CNS). The vast majority of PCNSLs are diffuse large B-cell lymphomas (DLBCLs). PCNSL is a highly heterogeneous disease, and its pathogenesis has not yet been fully elucidated. Further studies are needed to guide individualized therapy and improve the prognosis. METHODS: In this study, we detected 1) the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 by immunohistochemistry (IHC) and Western blotting, 2) the mRNA expression by real-time qPCR and 3) the deletion of PTEN gene by immunofluorescence in situ hybridization (FISH) in order to investigate the activation status of the PI3K/AKT/mTOR signaling pathway in PCNSL. Samples of reactive hyperplasia lymphnods were used as the control group. The correlations between the clinical characteristics and prognosis of PCNSL patients and the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 and the deletion of PTEN were assessed. RESULTS: The IHC results showed that the positive expression rates of p-AKT, p-mTOR, p-S6 and p-4E-BP1 in PCNSL were significantly higher in the PCNSL group than in the control group (P < 0.05). The relative mRNA expression level of MTOR in PCNSL samples was significantly increased (P = 0.013). Correlation analysis revealed that the expression of p-mTOR was correlated with that of p-AKT, p-S6, p-4E-BP1. PTEN deletion was found in 18.9% of PCNSL samples and was correlated with the expression of p-AKT (P = 0.031). Correlation analysis revealed that the PCNSL relapse rate in the p-mTOR-positive group was 64.5%, significantly higher than that in the negative group (P = 0.001). Kaplan-Meier survival analysis showed inferior progression-free survival (PFS) in the p-mTOR- and p-S6-positive groups (P = 0.002 and 0.009, respectively), and PTEN deletion tended to be related to shorter overall survival (OS) (P = 0.072). Cox regression analysis revealed p-mTOR expression as an independent prognostic factor for a shorter PFS (hazard ratio (HR) =7.849, P = 0.046). CONCLUSIONS: Our results suggest that the PI3K/AKT/mTOR signaling pathway is aberrantly activated in PCNSL and associated with a poor prognosis, which might indicate new therapeutic targets and prognostic factors.

Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis.

BACKGROUND: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Studies investigating primary CNSL determined that the Bruton tyrosine kinase (BTK) played an important role in pathogenesis. Ibrutinib, an oral BTK inhibitor, is a new treatment strategy for CNSL. The purpose of this meta-analysis was to clarify the effectiveness and safety of ibrutinib in the treatment of CNSL. METHODS: A systematic search of PubMed, Embase, Cochrane library, Wanfang Data Knowledge Service Platform, and China National Knowledge Infrastructure databases was conducted through to 31 October 2019. Studies involving patients with CNSL who received ibrutinib that reported the overall response (OR), complete remission (CR), and partial response (PR) were included. The random-effects or fixed-effects model with double arcsine transformation was used for the pooled rates and 95% confidence intervals (CI) were determined for all outcomes. RESULTS: Eight studies including 162 patients were identified and included in the meta-analysis. The pooled OR rate after treatment with ibrutinib was 69% (95% CI, 61-79%, I2 = 47.57%, p = 0.06), while the pooled CR and PR was 52% (95% CI, 35-68%, I2 = 74.95%, p = 0.00) and 17% (95% CI, 7-30%, I2 = 67.85%, p = 0.00), respectively. Among PCNSL patients, including new diagnoses PCNSL and R/R PCNSL, the pooled OR rate was 72% (95% CI, 63-80%, I2 = 49.20%, p = 0.06) while the pooled CR and PR rates were 53% (95% CI, 33-73%, I2 = 75.04%, p = 0.00) and 22% (95% CI, 14-30%, I2 = 46.30%, p = 0.07), respectively. Common adverse events above grade 3 included cytopenia and infections. CONCLUSIONS: The ibrutinib-containing therapy was well tolerated and offered incremental benefit to patients with CNSL. However, randomized-controlled studies that directly compare efficacy and adverse events of ibrutinib are still needed. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42020218974.

Treatment of secondary central nervous system involvement in systemic aggressive B cell lymphoma using R-MIADD chemotherapy: a single-center study.

BACKGROUND: Secondary central nervous system lymphoma (SCNSL) is defined as lymphoma involvement within the central nervous system (CNS) that originated elsewhere, or a CNS relapse of systemic lymphoma. Prognosis of SCNSL is poor and the most appropriate treatment is still undetermined. METHODS: We conducted a retrospective study to assess the feasibility of an R-MIADD (rituximab, high-dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, and dexamethasone) regimen for SCNSL patients. RESULTS: Nineteen patients with newly diagnosed CNS lesions were selected, with a median age of 58 (range 20 to 72) years. Out of 19 patients, 11 (57.9%) achieved complete remission (CR) and 2 (10.5%) achieved partial remission (PR); the overall response rate was 68.4%. The median progression-free survival after CNS involvement was 28.0 months (95% confidence interval 11.0-44.9), and the median overall survival after CNS involvement was 34.5 months. Treatment-related death occurred in one patient (5.3%). CONCLUSIONS: These single-centered data underscore the feasibility of an R-MIADD regimen as the induction therapy of SCNSL, further investigation is warranted.

Lymphodepletion chemotherapy revitalizes chimeric antigen receptor T cells contributing to regression of relapsed B-cell lymphoma: A case report.

INTRODUCTION: Chimeric antigen receptor T cells (CAR-T) targeting CD19 have shown great potential for treatment of B-cell malignancies. For those patients who can not achieve complete remission (CR) or suffer from relapse after CAR-T therapy, further therapeutic strategies still remain elusive. Whether existing CAR-T cells can revitalize in vivo and eradicate tumor cells is still unknown. PATIENT CONCERNS: We report a case of diffused large B-cell lymphoma patient who had achieved CR after CD19 targeted CAR-T therapy but relapsed after 5 months. DIAGNOSIS: Five months after CAR-T cell infusion, the patient was confirmed a relapse by follow-up PET/CT scan and a mass biopsy. Flow cytometry showed a dramatically decreased percentage of CAR-T cells in peripheral blood (PB). INTERVENTIONS: A second anti-CD19 CAR-T therapy was planned with deliberation. Firstly, the patient received lymphodepletion chemotherapy with fludarabine (25 mg/m, d1-d3) and cyclophosphamide (500 mg/m d2-d3). OUTCOMES: After fludarabine and cyclophosphamide (FC) lymphodepletion chemotherapy, pre-existing CAR-T cells were revitalized and the patient developed grade 2 cytokine release syndrome (CRS) contributing to the regression of relapsed B-cell lymphoma. CONCLUSIONS: This case suggested that FC chemotherapy could revitalize CAR-T cells contributing to the regression of relapsed B-cell lymphoma. Nevertheless, further researches are required in the future as this report described only a single case.

CAR T-cell treatment during the COVID-19 pandemic: Management strategies and challenges.

The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly across the world. Currently, the COVID-19 pandemic is affecting the continuity of essential routine healthcare services and procedures, including chimeric antigen receptor T-cell (CAR-T) therapy, a life-saving option for patients with relapsed/refractory (R/R) hematologic malignancies. Due to the rapid disease progression of hematological malignancies, there is an urgent need to manufacture and utilize CAR T-cells. However, CAR-T treatment has become extraordinarily challenging during this COVID-19 pandemic. Thus, many medical and technical factors must now be taken into consideration before, during, and after CAR-T therapy. The purpose of this review is to provide brief suggestions for rational decision-making strategies in evaluating and selecting CAR T-cell treatment and appropriate CAR T-cell products, and protective strategies for medical staff and patients to prevent infection in the midst of the current COVID-19 pandemic.

Expression of hypoxia-inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors.

BACKGROUND: It has been indicated that abnormal glucose metabolism mediated by hypoxia-inducible factor 1α (HIF-1α) played an essential role in the development of solid tumor. However, there were rare studies about the role of them in primary central nervous system lymphoma (PCNSL). OBJECTIVE: To investigate the protein levels of HIF-1α, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) in PCNSL and whether their levels are associated with prognostic factors. METHODS: Expression of HIF-1α, GLUT1, and HK2 in 39 tumor tissues was evaluated by immunohistochemical stainning. The correlation of the expression of HIF-1α with the protein level of GLUT1 and HK2 was investigated. In addition, the association between these protein expression levels and clinical parameters and prognosis was analyzed. RESULTS: In the tumor specimens of PCNSL, positive stainings of HIF-1α, GLUT1, and HK2 were in 23 patients (58.97%), 25 patients (64.1%), and 26 patients (66.67%), respectively, which were associated with the expression level of lactic dehydrogenase (LDH), but not with age, gender, number of lesion, ECOG score, or deep structure. The expression of HIF-1α was positively correlated with the expression of GLUT1 (p < .01, r = .749) and HK2 (p < .01, r = .787). Univariate analysis showed that upregulated GLUT1 was unfavorable predictors of progression-free survival (PFS) in PCNSL. The results of Cox proportional hazards model showed GLUT1 was significantly associated with shorter PFS (hazard ration: 5.65; 95% confidence interval: 1.23-25.84; p = .026). CONCLUSIONS: This study indicated that there was a hypoxic microenvironment and HIF-1α was involved in the regulation of glycolysis pathway in PCNSL. GLUT1 might be a potential marker for shorter PFS in PCNSL.

Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study.

BACKGROUND: Consolidative allogeneic hematopoietic stem cell transplantation is a controversial option for patients with relapsed/refractory acute lymphoblastic leukemia after chimeric antigen receptor T cell (CAR-T) therapy. We performed a multicenter retrospective study to assess whether patients can benefit from haploidentical hematopoietic stem cell transplantation after CAR-T therapy. METHODS: A total of 122 patients after CAR-T therapy were enrolled, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haploidentical hematopoietic stem cell transplantation (transplant group). Long-term outcome was assessed, as was its association with baseline patient characteristics. RESULTS: Compared with the non-transplant group, transplantation recipients had a higher 2-year overall survival (OS; 77.0% versus 36.4%; P < 0.001) and leukemia-free survival (LFS; 65.6% versus 32.8%; P < 0.001). Multivariate analysis showed that minimal residual disease (MRD) positivity at transplantation is an independent factor associated with poor LFS (P = 0.005), OS (P = 0.035), and high cumulative incidence rate of relapse (P = 0.045). Pre-transplant MRD-negative recipients (MRD- group) had a lower cumulative incidence of relapse (17.3%) than those in the non-transplant group (67.2%; P < 0.001) and pre-transplant MRD-positive recipients (MRD+ group) (65.8%; P = 0.006). The cumulative incidence of relapse in MRD+ and non-transplant groups did not differ significantly (P = 0.139). The 2-year LFS in the non-transplant, MRD+, and MRD- groups was 32.8%, 27.6%, and 76.1%, respectively. The MRD- group had a higher LFS than the non-transplantation group (P < 0.001) and MRD+ group (P = 0.007), whereas the LFS in the MRD+ and non-transplant groups did not differ significantly (P = 0.305). The 2-year OS of the MRD- group was higher than that of the non-transplant group (83.3% versus 36.4%; P < 0.001) but did not differ from that of the MRD+ group (83.3% versus 62.7%; P = 0.069). The OS in the non-transplant and MRD+ groups did not differ significantly (P = 0.231). CONCLUSION: Haploidentical hematopoietic stem cell transplantation with pre-transplant MRD negativity after CAR-T therapy could greatly improve LFS and OS in patients with relapsed/refractory acute lymphoblastic leukemia. TRIAL REGISTRATION: The study was registered in the Chinese clinical trial registry (ChiCTR1900023957).

Concentrations and accumulation rates of polychlorinated biphenyls in soil along an urban-rural gradient in Shanghai.

This study proposed an in situ soil experimental system to quantify concentration and accumulation rates of polychlorinated biphenyl (PCB) congeners in the soil in a rural-urban fringe and correlated them with multiple variables in the area. Variables, including road density, normalized difference vegetation index (NDVI), distance to the nearest highway and industrial area from the soil experimental sites, land-use impact index, population density, population change index (PCI), total population, and percentage of water area, were used to explain the concentration of different PCB congeners in soil during the experimental period. A proportion of 40.1%, 22.6%, 56.9%, and 34.3% accumulation rates of PCB8, PCB18, PCB28, and PCB118, respectively was explained by industrial developments, using stepwise linear regression analysis. NDVI was used to explain 33.6%, 61.5%, 49.1%, and 53.2% accumulation rates of PCB44, PCB101, PCB187, and PCB180, respectively. Filtering and transferring of airborne organic pollutants from atmosphere to soil by forests or tree stands and farmlands were all NDVI-related factors that affected the concentrations and accumulation rates of PCB congeners in soil. The traffic-related particle deposition might be the reason why the concentrations and accumulation rates of PCB congeners in soil were affected by road density. The findings can help quantitatively understand urbanization and the associated environmental effects. Graphic abstract.

STAT3 Activation Is Associated with Interleukin-10 Expression and Survival in Primary Central Nervous System Lymphoma.

BACKGROUND: The findings from several studies have confirmed that signal transducer and activator of transcription 3 (STAT3) is constitutively phosphorylated in primary central nervous system lymphoma (PCNSL). However, the underlying mechanism and prognostic significance of STAT3 activation have not yet been clarified. METHODS: The expression of STAT3, phosphorylated STAT3 (p-STAT3), and interleukin (IL)-10 was examined in 32 PCNSL samples using immunohistochemistry. The relationship between IL-10 expression and STAT3 phosphorylation was determined. In addition, the associations of the expression of these proteins with the clinical factors and survival were analyzed. RESULTS: Expression of STAT3, p-STAT3, and IL-10 was detected in 28 (87.5%), 17 (53.1%), and 25 (78.1%) samples, respectively. IL-10 expression was significantly associated with STAT3 phosphorylation in PCNSL (P = 0.033). STAT3 phosphorylation and IL-10 expression were associated with the presence of multiple brain lesions (P = 0.004 and P = 0.027, respectively), suggesting that STAT3 activation might enhance the intracranial spread of tumors in PCNSL. The 2-year overall survival and progression-free survival (PFS) rates were 67.8% and 35.5%, respectively. Kaplan-Meier survival analysis demonstrated that STAT3 phosphorylation, IL-10 expression, and multiple brain lesions were significantly associated with PFS in those with PCNSL (P = 0.009, P = 0.030, and P = 0.040, respectively). However, Cox regression analysis indicated that only STAT3 phosphorylation was significantly associated with shorter PFS (hazard ratio, 3.22; 95% confidence interval, 1.24-8.37; P = 0.016). CONCLUSION: Our results have indicated that STAT3 activation is closely related to IL-10 expression and that p-STAT3 might be a novel biomarker predictive of poor survival in those with PCNSL.

Parenchymal central nervous system involvement in aggressive B-cell lymphoma: retrospective analysis of clinical and MRI features in a Chinese population.

BACKGROUND: Secondary central nervous system lymphoma (SCNSL) is defined as secondary central nervous system (CNS) involvement in patients with systemic lymphoma. It is considered a profoundly adverse complication with inferior clinical outcome. Parenchymal involvement in the CNS in aggressive B-cell lymphoma is not frequently seen and remains a diagnostic dilemma. METHODS: In our study, we retrospectively analyzed the clinical and magnetic resonance imaging (MRI) features of 26 parenchymal SCNSL patients. In addition, we compared MRI features of SCNSL and primary CNS lymphoma (PCNSL) patients after 1:1 propensity score matching. Also we presented two SCNSL cases with atypical MRI appearance. RESULTS: Among SCNSL patients, the median CNS relapse time was 3 months, and multiple lesions were found in 76.9% of the cases. In PCNSL, this percentage was 42.3% (p = 0.011). None of the SCNSL patients and 23.1% of the PCNSL patients had solitary infratentorial lesions (p = 0.003). CONCLUSIONS: The majority of parenchymal involvement occurred within the first year of systemic lymphoma, in which mostly cases presenting with multiple and supratentorial locations, unlike what was found in PCNSL.

Delayed Terminal Ileal Perforation in a Relapsed/Refractory B-Cell Lymphoma Patient with Rapid Remission Following Chimeric Antigen Receptor T-Cell Therapy.

Chimeric antigen receptor T-cell strategy targeting CD19 (CART19) has prominent anti-tumor effect for relapsed/refractory B-cell lymphomas. CART19-associated complications have been gradually recognized, however, late-onset complications have not been extensively studied. Herein, for the first time we report a diffuse large B-cell lymphoma patient with terminal ileum involvement obtained rapid remission and developed spontaneous terminal ileal perforation 38 days following CART19 infusion. The late-onset perforation reminds us that, for the safety of CART treatment, more cautions are warranted for the management of delayed GI complications.