Adverse Reactions in Relapsed/Refractory B-Cell Lymphoma Administered with Chimeric Antigen Receptor T Cell Alone or in Combination with Autologous Stem Cell Transplantation.

(1) Background: The combination of CAR-T with ASCT has been observed to enhance the efficacy of CAR-T cell therapy. However, the impact of this combination on adverse reactions is still uncertain. (2) Methods: Between January 2019 and February 2023, 292 patients diagnosed with r/r B-cell lymphoma received either CAR-T therapy alone or in combination with ASCT at our institution. We evaluated the incidence of CRS and CRES and utilized a logistic regression model to identify factors contributing to severe CRS (grade 3-4) and CRES (grade 3-4). (3) Results: The overall incidence of CRS and CRES was 78.9% and 8.2% in 147 patients receiving CAR-T alone, and 95.9% and 15.2% in 145 patients receiving CAR-T combined with ASCT, respectively. The incidence of overall CRS (p < 0.0001) and mild CRS (grade 1-2) (p = 0.021) was elevated in the ASCT combined with CAR-T group. No significant difference was observed in severe CRS and CRES between the groups. Among the 26 cases of lymphoma involving the central nervous system (CNS), 96.2% (25/26) developed CRS (15.4% grade 3-4), and 34.6% (9/26) manifested CRES (7.7% grade 3-4). Female patients had a lower incidence of severe CRS but a higher incidence of severe CRES. Lymphomas with CNS involvement demonstrated a higher risk of CRES compared to those without central involvement. (4) Conclusions: The combination of ASCT with CAR-T demonstrated a preferable option in r/r B-cell lymphoma without an increased incidence of severe CRS and CRES.

Combination of chidamide and PD-1 blockade in Refractory/Relapsed aggressive large B-cell lymphomas with high risk of failing CAR-T therapy.

BACKGROUND: Refractoriness and relapse after chimeric antigen receptor T-cell therapy have emerged as major challenges for immunotherapy of aggressive large B-cell lymphoma. Thus far, there is no consensus on how to address treatment failure and whether to administer maintenance therapy following CAR-T cell therapy. METHODS: From August 2017 through November 2022, 52 patients with refractory/relapsed aggressive LBCL who had a high risk of resistance to CAR-T cell therapy were given chidamide in combination with a PD-1 inhibitor as maintenance therapy following either CAR19/22 T-cell cocktail therapy or CAR19/22 T-cell cocktail therapy plus autologous stem cell transplantation (ASCT). Another 52 aggressive LBCL patients who had comparable baseline characteristics and received similar therapeutic regimens but did not receive any interventions following CAR-T cell therapy or CAR-T cell therapy plus ASCT were regarded as the control group to evaluate the efficacy and safety of the combination of chidamide and a PD-1 inhibitor. RESULTS: Among the 52 patients who received chidamide and a PD-1 inhibitor as maintenance therapy, with a median follow-up of 26.5 months (range: 1.1-53.8), neither the median progression-free survival (PFS) nor overall survival (OS) was reached, and the expected 2-year OS and PFS rates were 89 % and 77 %, respectively, which were superior to those of the control group (p < 0.001). Long-term chidamide administration and a specific genetic subtype of EZB were strongly associated with a better response after chidamide plus PD-1 blockade therapy. Additionally, long-term chidamide administration was significantly associated with prolonged persistence and reactivation of CD19-directed CAR-T cells in the peripheral blood. Adverse effects (AEs) were moderate and reversible, and no treatment-related deaths occurred. CONCLUSION: Our results indicate that the combination of chidamide and PD-1 blockade as maintenance therapy could improve the outcomes of aggressive LBCL patients at high risk of failing CAR-T cell therapy.

Frontline combination of dasatinib and low-intensity chemotherapy in adults with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia.

BACKGROUND: Studies on dasatinib-based low-intensity induction regimens and post-remission strategies are limited in China. Therefore, we conducted a single-center phase 2 trial in newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) to establish the efficacy and safety of this treatment approach. RESEARCH DESIGN AND METHODS: Patients received one month of dasatinib plus low-intensity chemotherapy and two months of dasatinib monotherapy for induction, followed by a single course of high-dose methotrexate for consolidation. Subsequently, they underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) or tyrosine kinase inhibitor (TKI)-based treatment for maintenance therapy between October 2015 and August 2022. RESULTS: Twenty-two patients were enrolled. Median age was 45 years (range, 20-71). The rates of major and complete molecular responses in the third month were 18.2% and 40.9% respectively. With a median follow-up of 15 months (range, 5-89), the estimated 3-year disease-free survival (DFS) and overall survival (OS) were 52.4% and 73.2%, respectively. The TKI-based cohort had a significantly poorer DFS (p = 0.014) and OS (p = 0.008) than the allo-HSCT cohort. CONCLUSIONS: Our results suggest that dasatinib-based low-intensity chemotherapy is safe and effective as an induction strategy in the Chinese population. Allo-HSCT plays a crucial role in the long-term outcomes of patients with Ph+ ALL. CLINICAL TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov as NCT02690922.

Clinical performance of metagenomic next-generation sequencing for diagnosis of invasive fungal disease after hematopoietic cell transplant.

Background: Timely diagnosis and appropriate antifungal therapy are critical for improving the prognosis of patients with invasive fungal disease (IFD) after hematopoietic stem cell transplantation (HSCT). We evaluated the performance of metagenomic next-generation sequencing (mNGS) and conventional microbiological testing (CMT), as well as the diagnosis, therapeutic management, and outcomes of IFD after HSCT. Methods: We retrospectively studied 189 patients who underwent HSCT and were considered at risk for IFD. In total, 46 patients with IFD were enrolled in this study. The IFD consensus was followed for classifying IFD incidents. Results: Forty-six patients were diagnosed with proven/probable (n = 12), possible (n = 27), and undefined (n = 7) IFD. Aspergillus was the most commonly detected fungal genus. Mucormycosis was found in 15 patients; two had Aspergillus, and one had Candida infections. Compared to CMT, mNGS significantly reduced the time required to identify pathogens (P = 0.0016). mNGS had a much higher sensitivity than CMT (84.78% vs. 36.96%; P < 0.0001). A total of 76.09% of patients received antifungal prophylaxis during fungal infections. All Pneumocystis infections occurred later than 100 days after transplantation. Among patients with Pneumocystis infection, 71.43% occurred following sulfonamide withdrawal, and subsequent treatment with sulfonamide alone or in combination with other drugs was effective. Based on the empirical antifungal treatment, the dosages, modes of administration, frequency of administration, or antifungal of 55.26% of the patients were changed according to the mNGS results. The 4-year overall survival rate of patients diagnosed with IFD after transplantation was 71.55% (95% CI, 55.18%-85.82%). Hypoproteinemia and corticosteroid use are independent risk factors for IFD. Conclusion: mNGS, which has a high sensitivity and a short detection time, aids in the diagnosis and prognosis of pathogenic fungi. As a powerful technology, mNGS can influence treatment decisions in patients with IFD following HSCT.

Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma.

INTRODUCTION: Chimeric antigen receptor (CAR)-T cells obtained long-term durability in about 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Maintenance therapy after CAR-T is necessary, and PD1 inhibitor is one of the important maintenance therapy options. METHODS: A total of 173 r/r B-NHL patients treated with PD1 inhibitor maintenance following CD19/22 CAR-T therapy alone or combined with autologous hematopoietic stem cell transplantation (ASCT) from March 2019 to July 2022 were assessed for eligibility for two trials. There were 81 patients on PD1 inhibitor maintenance therapy. RESULTS: In the CD19/22 CAR-T therapy trial, the PD1 inhibitor maintenance group indicated superior objective response rate (ORR) (82.9% vs 60%; P = 0.04) and 2-year progression-free survival (PFS) (59.8% vs 21.3%; P = 0.001) than the non-maintenance group. The estimated 2-year overall survival (OS) was comparable in the two groups (60.1% vs 45.1%; P = 0.112). No difference was observed in the peak expansion levels of CD19 CAR-T and CD22 CAR-T between the two groups. The persistence time of CD19 and CD22 CAR-T in the PD1 inhibitor maintenance group was longer than that in the non-maintenance group. In the CD19/22 CAR-T therapy combined with ASCT trial, no significant differences in ORR (81.4% vs 84.8%; P = 0.67), 2-year PFS (72.3% vs 74.9%; P = 0.73), and 2-year OS (84.1% vs 80.7%; P = 0.79) were observed between non-maintenance and PD1 inhibitor maintenance therapy groups. The peak expansion levels and duration of CD19 and CD22 CAR-T were not statistically different between the two groups. During maintenance treatment with PD1 inhibitor, all adverse events were manageable. In the multivariable analyses, type and R3m were independent predictive factors influencing the OS of r/r B-NHL with PD1 inhibitor maintenance after CAR-T therapy. CONCLUSION: PD1 inhibitor maintenance following CD19/22 CAR-T therapy obtained superior response and survival in r/r B-NHL, but not in the trial of CD19/22 CAR-T cell therapy combined with ASCT.

Early Infant Prefrontal Cortical Microstructure Predicts Present and Future Emotionality.

BACKGROUND: High levels of infant negative emotionality (NE) and low positive emotionality (PE) predict future emotional and behavioral problems. The prefrontal cortex (PFC) supports emotional regulation, with each PFC subregion specializing in specific emotional processes. Neurite Orientation Dispersion and Density Imaging (NODDI) estimates microstructural integrity and myelination via the neurite density index (NDI) and dispersion via the orientation dispersion index (ODI), with potential to more accurately evaluate microstructural alterations in the developing brain. Yet, no study has used these indices to examine associations between PFC microstructure and concurrent or developing infant emotionality. METHODS: We modeled PFC subregional NDI and ODI at 3 months with caregiver-reported infant NE and PE at 3 months (n=61) and at 9 months (n=50), using multivariable and subsequent bivariate regression models. RESULTS: The most robust statistically-significant findings were positive associations among 3-month rACC ODI and cACC NDI and concurrent NE, and 3-month lOFC ODI and prospective NE; and a negative association between 3-month dlPFC ODI and concurrent PE. Multivariate models also revealed that other PFC subregional microstructure measures, and infant and caregiver sociodemographic and clinical factors, predicted infant 3- and 9-month NE and PE. CONCLUSIONS: Greater NDI and ODI, reflecting greater microstructural complexity, in PFC regions supporting salience perception (rACC), decision-making (lOFC), action selection (cACC), and attentional processes (dlPFC) might result in greater integration of these subregions with other neural networks, greater attention to salient negative external cues, thus higher NE and/or lower PE. These findings provide potential infant cortical markers of future psychopathology risk.

Overcoming the challenges encountered in CAR-T therapy: latest updates from the 2023 ASH annual conference.

Chimeric antigen receptor (CAR) -T cell therapy has entered the breakthrough era, characterized by a blend of therapeutic opportunities and challenges. With the integration of genome-editing technology, CAR-T cells will be empowered to become super warriors in eradicating tumor cells and attacking various tumors, including T-cell malignancies and acute myeloid leukemia. Notably, the optimization of CAR-T cells, including efficacy, safety, and manufacturing speed, coupled with other therapeutic strategies such as radiotherapy, hematopoietic stem cell transplantation, small-molecule inhibitors, and bispecific antibodies, could revolutionize the therapeutic landscape of tumors. Consequently, next-generation cellular immunotherapy, including universal CAR-NK cells and synergistic combination approaches, are anticipated to significantly impact cancer treatment in the coming decade. Nevertheless, the failure rates of CAR-T therapy continue to be significant. The challenge lies in determining the optimal combination strategy and identifying reliable and robust biomarkers to effectively select the patients who will derive the greatest benefit from CAR-T therapy. Herein, we highlight recent innovations in CAR-T products, combination strategies and predictive biomarkers of response presented at the 2023 ASH Annual Meeting.

High-multiplex single-cell imaging analysis reveals tumor immune contexture associated with clinical outcomes after CAR T cell therapy.

Chimeric antigen receptor (CAR) T cell therapy has made great progress in treating lymphoma, yet patient outcomes still vary greatly. The lymphoma microenvironment may be an important factor in the efficacy of CAR T therapy. In this study, we designed a highly multiplexed imaging mass cytometry (IMC) panel to simultaneously quantify 31 biomarkers from 13 patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) who received CAR19/22 T cell therapy. A total of 20 sections were sampled before CAR T cell infusion or after infusion when relapse occurred. A total of 35 cell clusters were identified, annotated, and subsequently redefined into 10 metaclusters. The CD4+ T cell fraction was positively associated with remission duration. Significantly higher Ki67, CD57, and TIM3 levels and lower CD69 levels in T cells, especially the CD8+/CD4+ Tem and Te cell subsets, were seen in patients with poor outcomes. Cellular neighborhood containing more immune cells was associated with longer remission. Fibroblasts and vascular endothelial cells resided much closer to tumor cells in patients with poor response and short remission after CAR T therapy. Our work comprehensively and systematically dissects the relationship between cell composition, state, and spatial arrangement in the DLBCL microenvironment and the outcomes of CAR T cell therapy, which is beneficial to predict CAR T therapy efficacy.

Nonrandom behavior in the projection of random bipartite networks.

There are two main categories of networks studied in the complexity physics community: Monopartite and bipartite networks. In this paper, we present a general framework that provides insights into the connection between these two classes. When a random bipartite network is projected into a monopartite network, under quite general conditions, the result is a nonrandom monopartite network, the features of which can be studied analytically. Unlike previous studies in the physics literature on complex networks, which rely on sparse-network approximations, we provide a complete analysis, focusing on the degree distribution and the clustering coefficient. Our findings primarily offer a technical contribution, adding to the current body of literature by enhancing the understanding of bipartite networks within the community of physicists. In addition, our model emphasizes the substantial difference between the information that can be extracted from a network measuring its degree distribution, or using higher-order metrics such as the clustering coefficient. We believe that our results are general and have broad real-world implications.

Recombinant Human Thrombopoietin Promotes Platelet Engraftment in Severe Aplastic Anemia Patients Following Treatment With Haploid Hematopoietic Stem Cell Transplantation using Modified Post-Transplantation Cyclophosphamide.

BACKGROUND: Recombinant human TPO (rhTPO) promotes platelet engraftment in patients after allogeneic HSCT (allo-HSCT). However, the effects of rhTPO on platelet recovery after Haplo-HSCT in patients with severe aplastic anemia (SAA) have not been intensively studied. OBJECTIVE: We aimed to evaluate the efficacy of rhTPO on platelet engraftment in patients with SAA who were treated with Haplo-HSCT using post-transplantation cyclophosphamide (PTCy). STUDY DESIGN: SAA patients who received Haplo-HSCT plus PTCy regimen were divided into the rhTPO group (with subcutaneous injection of rhTPO, n = 28) and Control group (no rhTPO administration, n = 27). The engraftment of platelet/neutrophil, platelet infusion amount, and transplant-related complications between the 2 groups were compared. RESULTS: All 55 patients showed successful hematopoietic reconstitution. The median time of platelet engraftment was 11 (9 to 29) days in the rhTPO group and 14 (9 to 28) days in the Control group (P = .003). The rhTPO group had a significantly reduced amount of infused platelets compared to the Control group (2 (1 to 11.5) versus 3 (1 to 14) therapeutic doses; P = .004). There was no significant difference between the 2 groups regarding median time of neutrophil engraftment, incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), incidence of cytomegalovirus or Epstein-Barr virus reactivation, 3-yr overall survival rate, and failure-free-survival rate. No obvious adverse reactions were observed in the rhTPO group. CONCLUSION: rhTPO promoted platelet engraftment, reduced the amount of transfused platelets, and demonstrated good safety profiles without evidence of adverse reactions in patients with SAA who received Haplo-HSCT using PTCy regimen.

Clinical analysis of 82 cases of acute promyelocytic leukemia with PML-RARα short isoform in children and adults.

Background: Acute promyelocytic leukemia (APL) with PML/RARα fusion gene is a distinct variant of acute myeloid leukemia. According to the different break sites of the PML gene, there are three transcripts: Long (bcr1), Variant (bcr2) and Short (bcr3). Methods: We retrospectively analyzed 82 APL cases with PML-RARα short isoform. Results: A total of 384 patients with APL were seen, of which 85(22.14%) had PML/RARα short isoform (bcr3) and 82 met the inclusion criteria. The median age was 33.5 years (range, 2-72 years). The incidences of hemorrhage in the intermediate- and high-risk group were higher, but only the incidence between medium and low risk differed statistically (P=0.006), and the incidences of fever, fatigue, splenomegaly, and lymph node enlargement and differentiation syndrome (DS) in those groups were not statistically significant (P>0.05). FLT3 gene mutation rate and the mortality rate of the high-risk group were significantly higher than that of other groups (P=0.040 and P=0.004, P=0.041 and P=0.037, respectively). The mortality rate was lowest (4.26%) in the group treated with ATRA combined with arsenic and anthracycline. The 3-year OS and the 3-year DFS of the low and intermediate-risk group were better (P=0.019 and P=0.017, respectively). Conclusions: ATRA combined with arsenic and anthracycline had significant impact on outcomes in APL with PML-RARα short isoform.

Finite barrier bound state.

A boundary mode localized on one side of a finite-size lattice can tunnel to the opposite side which results in unwanted couplings. Conventional wisdom tells that the tunneling probability decays exponentially with the size of the system which thus requires many lattice sites before eventually becoming negligibly small. Here we show that the tunneling probability for some boundary modes can apparently vanish at specific wavevectors. Thus, similar to bound states in the continuum, a boundary mode can be completely trapped within very few lattice sites where the bulk bandgap is not even well-defined. More intriguingly, the number of trapped states equals the number of lattice sites along the normal direction of the boundary. We provide two configurations and validate the existence of this peculiar finite barrier-bound state experimentally in a dielectric photonic crystal at microwave frequencies. Our work offers extreme flexibility in tuning the coupling between localized states and channels as well as a new mechanism that facilitates unprecedented manipulation of light.

Prognostic differences between carmustine, etoposide, cytarabine and melphalan (BEAM) and carmustine, etoposide, cytarabine, melphalan and fludarabine (BEAMF) regimens before autologous stem cell transplantation plus chimeric antigen receptor T therapy in patients with refractory/relapsed B-cell non-Hodgkin-lymphoma.

BACKGROUND AIMS: The combination therapy of autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CART) therapy has been employed to improve outcomes for relapsed or refractory (R/R) B-cell non-Hodgkin-lymphoma (B-NHL). The widely used conditioning regimen before ASCT plus CART therapy reported in the literature was carmustine, etoposide, cytarabine and melphalan (BEAM). However, whether adding fludarabine to the BEAM regimen (BEAMF) can improve the survival of patients with R/R B-NHL remains unknown. METHODS: In total, 39 and 19 patients with R/R B-NHL were enrolled to compare clinical outcomes in the BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy, respectively. RESULTS: The objective response (OR) rates at 3 months to BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy were 71.8% and 94.7%, respectively (P = 0.093). The BEAMF regimen showed a trend towards a superior duration of response compared with the BEAM regimen (P = 0.09). After a median follow-up of 28 months (range: 0.93-51.9 months), the BEAMF regimen demonstrated superior 2-year progression-free survival (PFS) (89.5% versus 63.9%; P = 0.048) and 2-year overall survival (OS) (100% vs 77.3%; P = 0.035) compared with the BEAM regimen. In the multivariable Cox regression analysis, OR at month 3 (responders) was remarkably correlated with better OS (hazard ratio: 0.112, P = 0.005) compared with OR (non-responders). CONCLUSIONS: For patients with R/R B-NHL, the BEAMF regimen before ASCT plus CD19/22 CART therapy was correlated with superior PFS and OS than the BEAM regimen, and the BEAMF regimen is a promising alternative conditioning regimen for ASCT plus CAR-T therapy.

PAA-PU Janus Hydrogels Stabilized by Janus Particles and its Interfacial Performance During Hemostatic Processing.

Hydrogel is a very promising dressing for hemostasis and wound healing due to its good adhesion and long-term moist environment. However, secondary injury caused by tissue adhesion due to homogeneous hydrogel cannot be ignored. The obvious interface existing in Janus hydrogel will weaken its asymmetric function. Here, a hierarchical adhesive polyacrylic acid-polyurushiol water-oil Janus hydrogel (JPs@PAA-PU) without adhesive layer is fabricated by one-pot method in the stabilization of polystyrene@silica-siliver Janus particles (JPs). The morphological structure, mechanical properties, anisotropic chemical composition, and adhesion performance, in vivo, and in vitro hemostatic properties of Janus hydrogel are investigated. Result shows that the obtained Janus hydrogel possesses obvious compartmentalization in microstructure, functional groups, and chemical elements. Janus hydrogel is provided with asymmetric interfacial toughness with top 52.45 ± 2.29 Kpa and bottom 7.04 ± 0.88 Kpa on porcine liver. The adhesion properties of PAA side to tissue, red blood cells and platelets, promoting effect of PU side on coagulation cascade reaction and its physical battier endow Janus hydrogel with shorter hemostatic time and less blood loss than control group. It also exhibits excellent antibacterial effects against Escherichia coli and Staphylococcus aureus (>90%). Janus hydrogel possesses biosafety, providing safety guarantee for clinical applications in the future.

Radical relay cyclization/C-C bond formation of allyloxy-tethered aryl iodides with quinoxalin-2(1H)-ones via polysulfide anion photocatalysis.

A visible-light-induced radical relay cyclization/C-C bond formation of quinoxalin-2(1H)-ones with allyloxy-tethered aryl iodides using polysulfide anions as a photocatalyst is described. This protocol allows efficient access to a variety of complicated molecules bearing both quinoxalin-2(1H)-one and 2,3-dihydrobenzofuran motifs in high yields under mild reaction conditions with a broad range of substrates.

The outcome and predictive model of allogeneic hematopoietic stem cell transplantation among elderly patients with severe aplastic anemia from the Chinese Blood and Marrow Transplant Registry Group.

Not available.

Efficient 3D imaging and pathological analysis of the human lymphoma tumor microenvironment using light-sheet immunofluorescence microscopy.

Rationale: The composition and spatial structure of the lymphoma tumor microenvironment (TME) provide key pathological insights for tumor survival and growth, invasion and metastasis, and resistance to immunotherapy. However, the 3D lymphoma TME has not been well studied owing to the limitations of current imaging techniques. In this work, we take full advantage of a series of new techniques to enable the first 3D TME study in intact lymphoma tissue. Methods: Diverse cell subtypes in lymphoma tissues were tagged using a multiplex immunofluorescence labeling technique. To optically clarify the entire tissue, immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO+), clear, unobstructed brain imaging cocktails and computational analysis (CUBIC) and stabilization to harsh conditions via intramolecular epoxide linkages to prevent degradation (SHIELD) were comprehensively compared with the ultimate dimensional imaging of solvent-cleared organs (uDISCO) approach selected for clearing lymphoma tissues. A Bessel-beam light-sheet fluorescence microscope (B-LSFM) was developed to three-dimensionally image the clarified tissues at high speed and high resolution. A customized MATLAB program was used to quantify the number and colocalization of the cell subtypes based on the acquired multichannel 3D images. By combining these cutting-edge methods, we successfully carried out high-efficiency 3D visualization and high-content cellular analyses of the lymphoma TME. Results: Several antibodies, including CD3, CD8, CD20, CD68, CD163, CD14, CD15, FOXP3 and Ki67, were screened for labeling the TME in lymphoma tumors. The 3D imaging results of the TME from three types of lymphoma, reactive lymphocytic hyperplasia (RLN), diffuse large B-cell lymphoma (DLBCL), and angioimmunoblastic T-cell lymphoma (AITL), were quantitatively analyzed, and their cell number, localization, and spatial correlation were comprehensively revealed. Conclusion: We present an advanced imaging-based method for efficient 3D visualization and high-content cellular analysis of the lymphoma TME, rendering it a valuable tool for tumor pathological diagnosis and other clinical research.

Improving the safety of CAR-T-cell therapy: The risk and prevention of viral infection for patients with relapsed or refractory B-cell lymphoma undergoing CAR-T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy, an innovative immunotherapeutic against relapsed/refractory B-cell lymphoma, faces challenges due to frequent viral infections. Despite this, a comprehensive review addressing risk assessment, surveillance, and treatment management is notably absent. This review elucidates immune response compromises during viral infections in CAR-T recipients, collates susceptibility risk factors, and deliberates on preventive strategies. In the post-pandemic era, marked by the Omicron variant, new and severe threats to CAR-T therapy emerge, necessitating exploration of preventive and treatment measures for COVID-19. Overall, the review provides recommendations for viral infection prophylaxis and management, enhancing CAR-T product safety and recipient survival.

Upper gastrointestinal tract immune-related adverse events: Two cases of obstructive complications occurred in immune consolidation therapy after sequential chimeric antigen receptor T cell therapy with autologous hematopoietic stem cell transplantation for refractory/relapsed diffuse large B cell lymphoma.

Key Clinical Message: Immune checkpoint inhibitors are a very popular method of treating malignant tumors. But its side effects cannot be ignored. This study revealed obstructive complications during immune consolidation therapy following sequential chimeric antigen receptor T cell therapy with autologous hematopoietic stem cell transplantation in two patients with diffuse large b cell lymphoma (DLBCL). Both our patients had the same symptoms of vomiting and inability to eat due to pyloric obstruction, it should be highlighted that this is a relatively rare and irreversible complication of upper gastrointestinal caused by immune consolidation therapy. Abstract: Immune checkpoint inhibitors (ICIs) have become the standard therapy for many malignant tumors.However, ICIs are associated with unique immune-related adverse events (irAEs) caused by dysregulated immune activation and associated complications have been observed in patients. Here, we report two cases of patients with pyloric obstruction and duodenal ulcers induced by the use of sintilimab, which provides some guidance for the widely used anti-programmed death-1 therapy. During the entire treatment progression for such patients, the correct differential diagnosis of adverse effects and the use of immunosuppressive agents such as glucocorticoids are essential to facilitate early prevention and intervention of irAEs.

Association Between Circulating Zinc and Risk for Childhood Asthma and Wheezing: A Meta-analysis on 21 Articles and 2205 Children.

Asthma is one of the most frequent chronic diseases in children, and growing focus is placed on the exploration of attributable risk factors. Currently, no consensus has been reached on the implication of circulating zinc in the development of asthma. We aimed to conduct a meta-analysis to examine the association between circulating zinc and risk for childhood asthma and wheezing. We searched PubMed, Web of Science, EMBASE, and Google Scholar from inception until December 1, 2022. All procedures were performed independently and in duplicate. Random-effects model was adopted to derive standardized mean difference (SMD) and 95% confidence interval (95% CI). Statistical analyses were completed using the STATA software. Twenty-one articles and 2205 children were meta-analyzed. Overall, there was a statistically significant association between circulating zinc and risk for childhood asthma and wheezing (SMD: -0.38; 95% CI: -0.60 to -0.17; I2=82.6%, p<0.001), without evidence of publication bias as revealed by Begg's (p=0.608) and Egger (p=0.408) tests. Subgroup analyses showed that children with asthma or wheezing in Middle Eastern countries had significantly lower circulating zinc levels than controls (SMD: -0.42; 95% CI: -0.69 to -0.14; p<0.001; I2=87.1%). Additionally, average circulating zinc levels in asthma children were 0.41 µg/dl lower than that in controls, and the difference was statistically significant (SMD: -0.41; 95% CI: -0.65 to -0.16; p<0.001; I2=83.7%). By contrast, children with wheezing were 0.20 µg/dl lower than that in controls, and no between-group difference was noted (SMD=-0.20; 95% CI: -0.58 to 0.17; p=0.072; I2=69.1%). Our findings indicated that circulating zinc was associated with a significant risk for childhood asthma and its related symptom wheezing.