Relapse and therapeutic resistance remain critical challenges in multiple myeloma (MM). This study investigates the macromolecular drivers of metabolic reprogramming in MM to identify novel therapeutic targets. Through integrated multi-omics profiling, we identified significant dysregulation in long-chain fatty acid metabolism, pinpointing the protein Acyl-CoA Synthetase Long-Chain Family Member 3 (ACSL3) as a central pathogenic factor. Clinical validation revealed that ACSL3 expression is significantly upregulated in MM cell lines and patient bone marrow compared to healthy controls, correlating with disease recurrence. Furthermore, in vitro and in vivo ACSL3 loss- and gain-of-function experiments established ACSL3 as a causal driver of MM cell survival. To elucidate the structural basis for targeting this macromolecule, we performed molecular docking simulations and surface plasmon resonance (SPR) assays. These integrated studies identified gramicidin as a novel direct inhibitor, revealing high-affinity binding interactions within the ACSL3 active site. Functional experimental validation demonstrated that targeting ACSL3 with gramicidin significantly suppressed MM growth in vitro and in vivo, induced apoptosis, and disrupted lipid metabolism. The observed effects were specifically rescued by ACSL3 overexpression. Additionally, we established a robust 8-metabolite signature that accurately predicts MM recurrence, outperforming standard clinical staging. This study characterizes the functional role of the biological macromolecule ACSL3 in MM pathogenesis and provides structural, biological, and preclinical evidence for its inhibition by gramicidin as a potential therapeutic strategy.

Objective:We aimed to develop a survival prediction system integrating radiomics and clinical features for newly diagnosed multiple myeloma (MM) and to compare the performance of different feature sets and algorithms in the early prediction of progression-free survival (PFS). Materials and Methods:This study retrospectively included 300 MM patients between June 2022 and June 2024, with their baseline positron emission tomography, computed tomography, and magnetic resonance imaging radiomics features and clinical variables collected. Following construction of a radiomics-based risk score (Rad-score), seven machine learning-based survival models were established using the clinical feature set, the image feature set, and the integrated feature set. Results:The fusion feature set-based gradient boosting model (GBM) showed numerically favorable overall performance in predicting 12-month PFS, suggesting that the integration of radiomics and clinical variables may provide complementary predictive information for early risk stratification. The model effectively distinguished high-, intermediate-, and low-risk patients (log-rank p<0.001), and calibration curve analysis and decision curve analysis revealed favorable calibration and high clinical net benefits. Shapley additive explanations analysis showed that the Rad-score was one of the most important features in the model, indicating that radiomics information may contribute prognostic value within the integrated feature space. β2-microglobulin, age, lactate dehydrogenase, blood calcium, platelet count, and hemoglobin were also identified as key contributing features. Conclusion:The integration of radiomics and clinical variables may improve early PFS prediction in MM patients. The GBM using fused features showed relatively good discriminative ability, potential clinical applicability, and favorable interpretability.

The specific prognostic impact of FLT3-ITD variant allele frequency (VAF) in acute myeloid leukemia (AML) remains unclear. In this multi-center study of 190 AML patients harboring FLT3-ITD mutations, a VAF cut-off of 40% was applied. Patients with high VAF (≥ 40%) exhibited significantly higher white blood cell counts, lactate dehydrogenase levels, and bone marrow blast percentages, alongside markedly shorter median overall survival (OS). Although high VAF was independently associated with inferior outcomes in the overall multivariate Cox regression analysis, its effect was profoundly amplified in the presence of co-mutations in NPM1 or DNMT3A. This suggests that high VAF may function not as an absolute, independent determinant, but primarily as a potent "risk amplifier." Notably, allogeneic hematopoietic stem cell transplantation (allo-HSCT) effectively mitigated this survival disadvantage. Furthermore, we characterized a non-linear relationship between VAF and mortality risk, with a sharp increase observed once the VAF burden exceeded 34%. In conclusion, a quantitative VAF ≥ 40% should be considered a context-dependent prognostic marker for risk stratification. Allo-HSCT represents a critical intervention capable of overcoming the exceedingly poor prognosis associated with high VAF.

BACKGROUND:Monoclonal gammopathy of undetermined significance (MGUS) is a precursor to multiple myeloma (MM), but the mechanisms of progression remain unclear. METHODS AND OBJECTIVES:Transcriptomic datasets procured from the Gene Expression Omnibus (GEO) underwent thorough analysis to ascertain disease-related modules using weighted gene co-expression network analysis. A prognostic model (MGUSscore) was constructed via least absolute shrinkage and selection operator (LASSO) regression within the GSE136337 cohort and validated across independent datasets (The Cancer Genome Atlas - multiple myeloma [TCGA-MM], GSE4581, GSE57317). Crucially, the investigation integrated original single-cell ATAC-seq profiling, immune landscape characterization, and pharmacogenomic sensitivity prediction. Protein-level disparities were validated in clinical specimens using immunohistochemistry and multiplex immunofluorescence. RESULTS:DAP3 and UBE2S were identified as central drivers of progression. The MGUSscore effectively stratified patients into risk categories, with high-risk individuals exhibiting significantly inferior survival outcomes (p < 0.001). Notably, the high-risk group was characterized by distinct immune infiltration patterns and predicted responsiveness to specific chemotherapies. Experimental validation confirmed markedly elevated DAP3 and UBE2S protein expression in MM compared to MGUS tissues. CONCLUSION:Collectively, DAP3 and UBE2S may constitute promising therapeutic targets for MM intervention, meriting additional investigative efforts.

This phase II clinical trial evaluated the R2-GemOx-PD1i regimen, a combination of penpulimab (a modified PD1 inhibitor) with lenalidomide and rituximab, gemcitabine, and oxaliplatin, in treating refractory or relapsed (R/R) diffuse large B-cell lymphoma (DLBCL). Patients received an induction treatment of up to six cycles of R2-GemOx-PD-1i at standard doses every 2 weeks, followed by pembrolizumab and lenalidomide as maintenance or autologous stem cell transplantation (ASCT) as consolidation. The primary objective was to evaluate the complete response rate (CRR) after the induction phase. Fifty-four patients were included, including subgroups treated without intent for consolidation with ASCT (N = 38) and those utilizing R2-GemOx-PD1i as a bridge to ASCT (N = 16). The overall response rate (ORR) for all patients was 66.7

Extramedullary multiple myeloma (EMM) is a severe complication involving tumor spread beyond the bone marrow. This study provides the first bibliometric analysis to systematically assess global EMM research trends. Publications (2000–2024) were retrieved from the Web of Science Core Collection and analyzed using VOSviewer, CiteSpace, and Bibliometrix. 963 publications (780 articles, 183 reviews) were identified, spanning four phases: exploratory (2000–2006), growth (2007–2010), volatile (2011–2019), and accelerated (2020–2024). The US leads with 292 papers, followed by China (146). Key institutions include the Mayo Clinic and University of Arkansas. Blood and Leukemia are top journals. Leading contributors include Einsele H and Rasche L, with high citation impact from Rajkumar SV. Six research themes emerged; current trends focus on PET/CT imaging and novel therapies like daratumumab and pomalidomide. Recent burst analysis (2020–2024) highlights diagnostic standardization and risk stratification. EMM research has shifted from descriptive studies to mechanistic and translational investigations aligned with precision medicine. Future efforts should prioritize multidisciplinary collaboration, real-world evidence, and innovative targeted therapies to address remaining clinical challenges.

Background:Hemophagocytic lymphohistiocytosis (HLH) is a fatal disorder characterized by uncontrolled inflammation. In adults, lymphoma is the most common underlying cause. The lipid profile is frequently dysregulated in lymphoma-associated HLH (LA-HLH), and the clinical significance remains to be determined. Objectives:This study aimed to evaluate the prognostic value of baseline lipid profiles and the dynamic changes in high-density lipoprotein cholesterol (HDL-c) in adult patients with LA-HLH. Design:A multicenter, retrospective cohort study. Methods:We analyzed 277 adult patients with LA-HLH from 27 medical centers (2015-2023). Baseline lipid levels and post-treatment HDL-c levels were measured. The optimal prognostic cutoff was determined using X-tile software. Survival analysis was performed using Kaplan-Meier and Cox regression methods. Results:Low HDL-c (<1.03 mmol/L) was observed in 93.9% (260/277) patients at diagnosis. A baseline HDL-c <0.48 mmol/L was independently associated with reduced overall survival (OS; hazard ratio, HR = 1.51, 95% confidence interval, CI: 1.10-2.09, p = 0.012) and 60-day survival (HR = 1.66, 95% CI: 1.10-2.49, p = 0.015). The post-treatment/baseline HDL-c ratio was significantly lower in patients with T/NK-cell malignancies than in those with B-cell non-Hodgkin lymphoma. A lower ratio (<1.71) was significantly associated with reduced survival. Patients with both low baseline HDL-c (<0.48 mmol/L) and low ratio (<1.71) constituted a high-risk group with the worst outcomes (60-day survival: 46.7% vs 81.8%, p = 0.004; median OS: 52 days vs not reached, p < 0.001). Conclusion:HDL-c and its dynamic changes are clinically feasible markers for predicting outcomes in patients with LA-HLH.

Diffuse large B-cell lymphoma (DLBCL), the most common aggressive non-Hodgkin lymphoma, urgently requires novel biomarkers for clinical diagnosis and therapeutic monitoring. Plasma exosomes from three DLBCL patients and three healthy controls were isolated via ultracentrifugation, and differentially expressed circular RNAs (circRNAs) were screened using Arraystar V2 microarrays (fold change [FC] ≥ 1.2, P ≤ 0.05). Candidate circRNAs were validated by quantitative real-time PCR (qRT-PCR) in 55 DLBCL patients and 25 controls. Microarray analysis identified 269 dysregulated circRNAs (152 upregulated, 117 downregulated; FC ≥ 1.2, P ≤ 0.05). RT-qPCR confirmed significantly elevated expression of hsa_circ_400230, hsa_circ_001393, and hsa_circ_404447 in DLBCL (P < 0.05), with areas under the ROC curve (AUCs) of 0.7622, 0.7244, and 0.6618, respectively. High hsa_circ_001393 expression correlated with advanced age (> 60 years), stage III/IV, high International Prognostic Index (IPI 3–5), elevated β2-microglobulin (> 2 mg/L), and non-complete remission (Non-CR) status (P < 0.05). Combined detection with lactate dehydrogenase (LDH) improved predictive efficacy (AUC = 0.817, P = 0.002). Post-chemotherapy complete remission (CR) patients exhibited significant reduction in hsa_circ_001393 (P = 0.0174). Competing endogenous RNA (ceRNA) network analysis identified MLLT3 as a hub gene, with overexpression associated with shorter survival (hazard ratio [HR] = 2.31, P = 0.0042). These findings demonstrate that Plasma exosomal hsa_circ_400230/001393/404,447 are novel diagnostic biomarkers. hsa_circ_001393 predicts therapeutic resistance and dynamically reflects chemotherapy response, potentially via the hsa-miR-1290/MLLT3 axis. This study advances liquid biopsy strategies for DLBCL management.

To investigate the efficacy of Iptacopan in transplantation-associated thrombotic microangiopathy (TA-TMA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), we report the case of a 43-year-old male with Acute Myeloid Leukemia, Myelodysplasia-Related (AML-MR, with IDH1 and STAG2 mutations) who developed TA-TMA after allo-HSCT. The patient had an initial partial response to the C5 inhibitor eculizumab, but the disease progressed. Oral Iptacopan (200 mg twice daily) was initiated on Day +36. The patient received a total of six sessions of therapeutic plasma exchange and two concurrent doses of defibrotide during the Iptacopan course. After 30 days of Iptacopan treatment, the patient exhibited a significant hematological response, evidenced by a reduction in LDH (758 U/L to 357 U/L), a rise in platelets (17 to 43×109/L), and a drop in C5b-9 (305.32 to 153.70 ng/mL). This biochemical improvement coincided with key clinical outcomes: resolution of proteinuria and the achievement of sustained red blood cell transfusion independence after day +58 and platelet transfusion independence after day +66, marking a decisive turnaround in his TA-TMA course. Treatment with the novel oral complement inhibitor Iptacopan induced significant hematological and clinical responses in this TA-TMA patient, demonstrating its potential therapeutic efficacy and warranting further clinical investigation.

ABSTRACT:Patients with relapsed or refractory multiple myeloma (RRMM) with extraosseous extramedullary disease (EMD) have inferior outcomes and lack effective therapies. We developed anti-B-cell maturation antigen (anti-BCMA)/G protein-coupled receptor, class C group 5 member D (GPRC5D) bispecific chimeric antigen receptors (CARs) to investigate the activity and safety of the CAR T cells in patients with extraosseous EMD. In this single-arm, open-label, phase 2 trial, we enrolled 37 patients with RRMM with extraosseous EMD, and anti-BCMA/GPRC5D bispecific CAR T cells were administered at 2.0 × 106 CAR T cells per kg. At a median follow-up of 10.1 months (interquartile range, 6.4-19.1), 36 of 37 patients (97%) obtained an overall response and measurable residual disease negativity, including 16 (43%) with stringent complete response. The median progression-free survival was 5.8 months (95% confidence interval, 2.2-9.4), and the median overall survival was not reached. The most common grade 3 or worse adverse events were hematologic toxicities (except lymphopenia; 37/37). Twenty-seven patients (73%) experienced cytokine release syndrome, all cases of which were grade 1 or 2. Two patients (5%) had grade 1 or 3 immune effector cell-associated neurotoxicity syndrome. These findings support that anti-BCMA/GPRC5D bispecific CAR T cells induced a high response rate in patients with RRMM with extraosseous EMD, and the safety profile was manageable. This ongoing trial is registered at www.clinicaltrials.gov as NCT05509530.

To identify risk factors for secondary acute myeloid leukemia (sAML) transformation in myeloproliferative neoplasms (MPN), determine prognostic factors, and construct a reliable prognostic risk model, this study performed a retrospective analysis using the US Surveillance, Epidemiology, and End Results (SEER) database. Multivariable competing risk regression revealed that female (HR = 0.84, P = 0.012), polycythemia vera (PV, HR = 0.29, P < 0.0001) or essential thrombocythemia (ET, HR = 0.26, P < 0.0001) were protective factors against sAML transformation. In contrast, American Indian/Alaska Native/Asian Pacific Islander (AIAN/API) race (HR = 1.31, P = 0.034), household income <70,000 (HR = 1.21, P = 0.022), chemotherapy history (HR = 1.80, P < 0.0001), and MPN diagnosis during 2011–2022 (HR = 1.29, P = 0.0001) were risk factors for leukemic transformation. Multivariate Cox proportional hazards regression showed that MPN-phase chemotherapy (HR = 1.25, P = 0.002), MPN diagnosis at age 60–75 years (HR = 1.34, P = 0.012), and sAML diagnosis at age ≥ 75 years​ (HR = 1.83, P = 0.001) were independent risk factors for post-progression survival (PPS) in patients with MPN-sAML. while sAML-phase chemotherapy was an independent protective factor (HR = 0.39, P < 0.001). Subgroup analysis revealed heterogeneity in prognostic factors among different sAML subgroups, but the protective effect of sAML-phase chemotherapy was consistently observed across all subgroups. Further multivariable Cox proportional hazards subgroup analysis suggested heterogeneity in the benefit of sAML-phase chemotherapy across age groups (P for interaction = 0.041), with attenuated benefit observed in patients aged 60–75 years (HR = 0.41) and ≥ 75 years (HR = 0.42) compared to younger patients aged 20–60 years (HR = 0.17). The prognostic risk model constructed based on independent prognostic factors and MPN subtypes can effectively stratify patients and provide a reference for risk stratification in patients with MPN-sAML.

​Approximately 30% to 40% of patients with Diffuse Large B-cell Lymphoma (DLBCL) experience treatment failure, whereas the current International Prognostic Index (IPI) fails to adequately reflect the intrinsic biological features. This study aimed to investigate the prognostic value of Replication Factor C genes (RFCs) in DLBCL and construct a prognostic risk model. Three DLBCL datasets were downloaded from the Gene Expression Omnibus (GEO) database (GSE181063, GSE10846, GSE31312). Multivariate Cox proportional hazards regression analysis identified high expression of RFC2 and RFC4 as independent adverse prognostic factors (RFC2: HR = 1.46, P = 0.037; RFC4: HR = 1.36, P = 0.034), which were significantly associated with age ≥ 60 years, elevated lactate dehydrogenase (LDH) levels, and poor Eastern Cooperative Oncology Group (ECOG) performance status. Mechanistically, the RFC2 high-expression group exhibited a significant increase in tumor mutational burden (TMB). Protein-protein interaction (PPI) analysis revealed that RFC2 and RFC4 interact with CHTF18, PCNA, and other proteins to maintain genomic stability. Gene set enrichment analysis (GSEA) indicated that RFC2 and RFC4 high-expression groups were enriched in the DNA replication and DNA damage repair (DDR) pathways. Competing endogenous RNA (ceRNA) network analysis predicted miR-34a-5p as an upstream regulator; PARD6G-AS1, TERC, and LINC00662 upregulating RFC2 and RFC4 by sponging miR-34a-5p. The RFC-based prognostic model significantly stratified high- and low-risk patients, with superior predictive performance compared to the IPI score. Validation in our clinical cohort confirmed that the high-risk group had significantly shorter overall survival (OS) (P = 0.003). This study provides a novel tool for individualized prognostic assessment in DLBCL and suggests RFC2 and RFC4 as potential therapeutic targets.

Background:Manganese (Mn), an essential trace element, is involved in various biological processes (BPs). The abnormal metabolism of Mn may be related to the occurrence and development of blood disease. In recent years, studies on manganese metabolism-related genes (MRGs) and acute myeloid leukemia (AML) have gradually attracted attention. The interaction between the immune system and AML is complex. The immune system not only participates in the occurrence and development of leukemia, but also affects the treatment response and prognosis of AML patients. This study aimed to establish a prognostic risk model for AML by combining MRGs and immune-related genes (IRGs). Methods:We constructed a prognostic risk model through univariate and multivariate Cox regression analyses, and validated the predictive efficacy of this model using external datasets. We analyzed the differences in immune infiltration between the high- and low-risk groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted to investigate the roles of five Mn metabolism- and immune-related genes (MIRGs). We also analyzed the immune checkpoint expression levels in AML. The expression levels of the five MIRGs in specific cells were analyzed through single-cell RNA sequencing. All the data analyses were conducted using R software version 4.2.2. Results:This study developed a prognostic risk model based on five MIRGs (CGA, TGFA, GKN1, S100G, and CCL23) linked to cytokine signaling and viral protein interactions. The model, along with age and cytogenetic risk, independently predicted the outcomes of the AML patients. Additionally, the high- and low-risk groups showed distinct immune infiltration patterns and immune checkpoint expression. Conclusions:Our study established an MIRG-based prognostic risk model that can effectively predict the prognosis of AML patients.

Background: MiR-106a and miR-20a (miR-17 family members) are frequently dysregulated in carcinogenesis, but their prognostic significance in acute myeloid leukemia (AML) remains unclear.Methods: We analyzed miR-106a and miR-20a expression in bone marrow from 115 AML patients and 45 healthy controls using qRT-PCR. Additionally, we utilized TCGA data (n=188) to assess the association of these miRNAs with clinical factors and outcomes. Prognostic analysis evaluated the impact of miR-106a and miR-20a on overall survival (OS) and event-free survival (EFS). Differentially expressed genes (DEGs) were identified using Limma. GO and KEGG pathway analyses were performed by DAVID. GSEA and PPI were constructed using ClusterProfiler and STRING database.Results: MiR-106a and miR-20a elevated in AML versus healthy controls. In chemotherapy group, miR-106ahigh or miR-20ahigh predicted poor OS and EFS, with dual-high expression conferring the worst outcome. In allo-HSCT group, miR-106ahigh or miR-20ahigh predicted poor OS but similar EFS, with dual-high cases showing the worst OS. In the miR-106ahigh or miR-20ahigh group, allo-HSCT prolonged OS (but not EFS) versus chemotherapy. In the miR-106alow or miR-20alow group, there were no obvious differences in OS or EFS between the chemotherapy and allo-HSCT regimens. Multivariable analyses confirmed miR-106a/miR-20a signature as an independent prognostic marker. Moreover, we identified 706 signature-associated DEGs. Bioinformatic analysis illuminated the involvement of miR-106a and miR-20a in regulating diverse biological processes and signaling pathways.Conclusions: MiR-106a and miR-20a are promising AML prognostic biomarkers for adverse outcome. The combined signature improves risk stratification and guides therapy selection (e.g., ⁣allo-HSCT for high-risk cases).

Abstract Background: QHRD107, a potent CDK9 inhibitor, has demonstrated promising activity in relapsed/refractory acute myeloid leukemia (R/R AML). The 107VA regimen, a triple combination of QHRD107, venetoclax (VEN) and azacitidine (AZA), has showed favorable safety profile. With enrollment now completed, we report updated efficacy and long-term survival data. Methods: This phase 2a, open-label, multicenter study (NCT06532058) consisted of a dose escalation phase and expansion phase. Patients with R/R AML were enrolled and received QHRD107 at one of three dose levels (40 mg, 60 mg, or 80 mg, PO, Q12 hours, days 1-28 in combination with AZA (75 mg/m2, days 1-7) and VEN (400 mg with dose ramp-up, days 1-28). The primary objective of the dose escalation phase was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), while the expansion phase focused on assessing composite complete remission rate (cCR) and duration of response (DOR). Results: Between August 2023 and February 2025, a total of 61 patients underwent screening, with 53 included in the intention-to-treat population. No dose-limiting toxicities (DLTs) were observed during the dose escalation phase, establishing 80mg of QHRD107 twice daily as the MTD. Due to gastrointestinal toxicity, patients were randomized 1:1 to receive QHRD107 at 60mg or 80mg during the expansion phase. The median age of the cohort was 60 years (range: 19-80), with 24 (45.3%) patients being male. Cytogenetic information was available in 49 (92.5%) patients, and next-generation sequencing results were available in all patients. At baseline, 7 (13.2%) patients had a RUNX1::RUNX1T1 fusion gene, 8 (15.1%) had an NPM1 mutation, 10 (18.9%) had a CEBPA bZIP mutation, 5 (9.4%) had a FLT3-ITD mutation and 6 (11.3%) had a TP53 mutation. Seven patients (13.2%) were classified as AML with myelodysplasia-related gene mutations/cytogenetic abnormalities (AML-MR) according to 2022 ELN recommendation. A total of 39 (73.6%) patients had been previously exposed to BCL-2 inhibitors (venetoclax or sonrotoclax), with 35 (66.0%) being refractory or relapsed from VEN-AZA regimen. Three patients in the expansion phase terminated treatment before cycle 1 day 28. Response rates were similar between the 60 and 80mg groups, with no obvious dose-dependent trend. Among 50 efficacy-evaluable patients, the overall response rate (ORR) was 54.0% (CR: 4, CRh: 7, CRi: 9, MLFS: 4, PR: 3), with a cCR rate of 40.0%. Measurable residual disease (MRD) negativity by flow cytometry was achieved in 9 responding patients. Subgroup analysis revealed response differences among patients with different genotypes. Patients with TP53 mutation and AML-MR showed higher response rates, with ORR of 66.7% and 100%, respectively. In contrast, patients with solo NPM1 mutation or NPM1 and FLT3-ITD co-mutations showed lower response rates. Notably, patients who were refractory or relapsed from VEN-AZA treatment achieved high response rates, with cCR rate of 34.3% (12 of 35) and ORR of 54.3% (19 of 35). Among these patients, all 5 AML-MR patients and 4 TP53-mutated patients achieved treatment responses. Three (6%) patients proceeded to allogeneic stem cell transplant and 2 patients received autologous stem cell transplant. The median overall survival (OS) was 12.9 months (95% CI: 5.4 to not reached) vs 13.5 months (95% CI: 3.5 to not reached) in the QHRD107 60mg and 80mg groups, respectively. Conclusions: The 107VA regimen demonstrated high response rates in VEN-AZA relapse or refractory AML, particularly in patients with TP53 mutations and myelodysplasia-related features. Based on these data, a phase 2b randomized controlled study comparing 107VA with other salvage regimens is currently being conducted for patients who relapse after VEN-AZA treatment.

OBJECTIVE:To investigate the predictive value of thromboelastogram(TEG) combined with blood D-dimer in patients with diffuse large B-cell lymphoma(DLBCL) complicated with venous thromboembolism(VTE) of lower extremities. METHODS:A total of 155 patients diagnosed with DLBCL in our hospital from August 2022 to August 2024 were collected as the research objects. Among them, 73 patients received lower extremity arteriovenous color Doppler ultrasound, and 14 patients with lower extremity venous thrombosis were detected, 59 cases were not detected, which were included in the VTE group and non-VTE group, respectively. The TEG parameters including coagulation angle(Angle), comprehensive coagulation index(CI), clotting time(K), maximum amplitude(MA), coagulation reaction time(R), together with blood D-dimer level, international prognostic index and whether it was relapsed or refractory were compared between the two groups. Multivariate Logistic regression analysis was used to explore the independent influencing factors of VTE formation in all patients. The area under the curve(AUC) of the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of each parameter for VTE. RESULTS:There was no significant difference in gender and age between the VTE group and the non-VET group (all P >0.05). The number of high-risk and relapse/refractory patients in the VTE group was significantly higher than that in the non-VTE group(all P < 0.05). Angle and CI in VTE group were significantly higher than those in non-VTE group(all P < 0.05), K value and R value were significantly lower than those in non-VTE group(all P < 0.05), and blood D-dimer level was significantly higher than that in non-VTE group (all P < 0.05). Multivariate logistic regression analysis showed that R value was an independent protective factor for VTE in patients with DLBCL (OR =0.256, P < 0.05 ), however, Ann Arbor stage (OR =3.885, P < 0.05 ) was independent risk factors for VTE in patients with DLBCL. The results of ROC curve analysis showed that there was no significant difference in the sensitivity of TEG (TEG group) prediction and TEG combined with blood D-dimer level (combined group) in predicting VTE in patients with DLBCL (92.86%,85.71%) and the sensitivity of blood D-dimer level (D-dimer group) prediction (71.43%) (P >0.05). There was no significant difference in the specificity between TEG group prediction (74.58%) and combined group prediction (81.36%), TEG group prediction and D-dimer group prediction ( 64.41 % ) (P >0.05). However, the specificity of the combined group was higher than that of the D-dimer group (χ2=4.288, P < 0.05). The AUC of the TEG group (0.901) and the combined group (0.915) was higher than that of the D-dimer group (0.692) ( Z=2.647, P < 0.05; Z=3.106, P < 0.05), but there was no significant difference in AUC between TEG group prediction and combined group prediction (P >0.05). CONCLUSION:TEG and blood D-dimer levels have certain predictive efficacy for VTE in DLBCL patients, but TEG combined with blood D-dimer level has higher clinical value for VTE in DLBCL patients, which is worthy of clinical promotion.

BACKGROUND:For patients with multiple myeloma progression after anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, the optimal salvage treatment strategies remain unclear. GPRC5D-directed CAR T cell might be a potential option. The aim of this trial was to investigate the activity and safety of anti-GPRC5D CAR T cells in patients with progressive multiple myeloma after anti-BCMA CAR T-cell therapy. METHODS:In this phase 2, open-label, single-arm, phase 2 trial, at the Affiliated Hospital of Xuzhou Medical University in China, we enrolled patients (aged 18-70 years old) with relapsed or refractory multiple myeloma who had progressed disease after anti-BCMA CAR T-cell therapy and a life expectancy of more than 12 weeks without active infections, serious liver, heart, or other diseases. Patients were assigned to receive a single dose of intravenous anti-GPRC5D CAR T cell at 2 × 106 cells per kg. The primary endpoint was the overall response rate, including stringent complete response, complete response, very good partial response, and partial response, according to the standard International Myeloma Working Group response assessment criteria. Activity and safety analyses were done in the patients who received a dose of anti-GPRC5D CAR T cell as defined in the protocol. This trial is registered with the Chinese Clinical Trial Registration Center, ChiCTR2100048888, and is ongoing. FINDINGS:Between Dec 1, 2021, and May 1, 2024, 42 patients were screened, 37 were enrolled and received anti-GPRC5D CAR T-cell therapy. Median age was 59 years (IQR 51-65), 17 (46%) of 37 patients were male and 20 (54%) female. All patients were Asian. At a median follow-up of 12·6 months (IQR 8·2-20·8), the overall response rate was 84% (95% CI 68-94, 31 of 37 patients), including 13 (35%) complete responses or better. The most common grade 3-4 adverse events were haematological toxicities, including leukopenia (34 [92%] of 37 patients), lymphopenia (36 [97%]), neutropenia (29 [78%]), anaemia (23 [62%]), and thrombocytopenia (23 [62%]). 26 (70%) of 37 patients had cytokine release syndrome, which was of grade 3 in two (5%) patients. One case of grade 1 immune effector cell-associated neurotoxicity syndrome was observed. There were no treatment-related deaths in the trial. INTERPRETATION:Anti-GPRC5D CAR T-cell salvage therapy induced a high response rate, and could be a potential treatment option in relapsed or refractory multiple myeloma patients who have progressed after anti-BCMA CAR T-cell treatment. Further investigations are warranted to establish the long-term efficacy and safety of this therapeutic approach. FUNDING:National Natural Science Foundation of China and the General Project of Jiangsu Commission of Health.