Behçet disease (BD) is a chronic systemic vasculitis with unclear etiology and pathogenesis. The incidence of arterial lesions is relatively low in patients with BD. This article summarizes the pathogenesis, pathological features as well as medical and surgical treatment methods of BD complicated with arterial lesions, so as to provide more new ideas for the comprehensive treatment of such patients.
ObjectiveTo analyze the efficacy and safety of prophylactic administration of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) before chimeric antigen receptor T cell (CAR-T) infusion in patients with multiple myeloma (MM). MethodsA retrospective analysis was conducted on 67 patients with relapsed/refractory multiple myeloma (RRMM) who received B-cell maturation antigen (BCMA)-targeted or BCMA/CD19 dual-targeted CAR-T therapy. Patients were divided into a PEG group (n=32, receiving a single subcutaneous injection of PEG-rhG-CSF one day before infusion) and a control group (n=35) according to whether PEG-rhG-CSF was prophylactically administered before CAR-T cell infusion. Hematopoietic recovery, neutropenia-related outcomes, immune reconstitution, adverse events, CAR-T expansion, efficacy, and hospitalization were compared between the two groups. ResultsThere was no statistically significant difference in the incidence of leukopenia or neutropenia between the two groups. The neutrophil nadir in the PEG group was higher than that in the control group (0.59×109/L vs. 0.20×109/L, P=0.0018), the median time to neutrophil recovery was shorter than that in the control group (15.0 d vs. 20.5 d, P=0.0052), and the duration of neutropenia was shorter than that in the control group (14 d vs. 19 d, P=0.0036). The incidences of agranulocytosis (34.4% vs. 74.3%, P=0.001) and febrile neutropenia (28.1% vs. 65.7%, P=0.0021) in the PEG group were lower than those in the control group. At 1 month after CAR-T cell infusion, the CD3+ and CD8+ T cell counts in the PEG group were higher (both P<0.05). The median hospital stay in the PEG group was significantly shorter than that in the control group (16 d vs. 21 d, P=0.0377). There were no statistically significant differences between the two groups in the incidence or severity of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome, nor in CAR-T expansion, overall response rate, or survival outcomes. ConclusionsProphylactic administration of PEG-rhG-CSF before CAR-T infusion in patients with RRMM is associated with a higher neutrophil nadir, a shorter time to neutrophil recovery, and lower incidences of agranulocytosis and febrile neutropenia. No increase in CAR-T-related adverse events or impairment of short-term antitumor efficacy or prognosis was observed with this intervention.
ObjectiveTo analyze the related factors affecting the efficacy of autologous peripheral blood stem cell mobilization and first collection outcomes in patients with multiple myeloma. MethodsClinical data of 25 patients with multiple myeloma who received autologous peripheral blood stem cell mobilization at the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University from January 2019 to December 2023 were retrospectively collected. Patients were grouped according to age, gender, disease type [immunoglobulin (Ig) G, IgA, IgD, and light-chain type], disease stage [Durie-Salmon (DS) staging system stage Ⅰ+Ⅱ and Ⅲ; International Staging System (ISS) stage Ⅰ+Ⅱ and Ⅲ], disease status before mobilization, number of induction treatment courses, and mobilization regimen. The differences in the number of CD34+ cells collected at the first collection were compared among groups. The time from mobilization to first collection, days of granulocyte colony-stimulating factor (G-CSF) use, hospitalization days, hospitalization costs, time to neutrophil engraftment, time to platelet engraftment, and adverse reactions were compared between the G-CSF plus plerixafor group and the G-CSF plus chemotherapy group. ResultsThe differences in the number of CD34+ cells collected were not statistically significant among groups stratified by age, gender, disease type, disease stage, disease status before mobilization, number of induction treatment courses, and mobilization regimen (all P>0.05). The time from mobilization to first collection, days of G-CSF use, and hospitalization days were all longer in the G-CSF plus chemotherapy group than in the G-CSF plus plerixafor group [(13.670±3.551) d vs. (4.820±0.555) d, P<0.001; (6.000±1.348) d vs. (5.000±0.557) d, P=0.023; 17–34 d vs. 10–17 d, P<0.001], while hospitalization costs were lower in the G-CSF plus chemotherapy group than in the G-CSF plus plerixafor group [(43 071±4 829) yuan vs. (85 846±11 444) yuan, P=0.003]. There was no statistically significant difference in the time to neutrophil engraftment or time to platelet engraftment between the two groups (P=0.091, 0.764). ConclusionsAge, gender, disease type, disease stage, disease status before mobilization, number of induction treatment courses, and mobilization regimen were not significantly associated with the number of CD34+ cells collected. The time from mobilization to collection, days of G-CSF use, and hospitalization days were shorter in the G-CSF plus plerixafor group, but the treatment cost was higher.
ObjectiveTo analyze the clinical characteristics, treatment and prognostic-related factors in newly diagnosed multiple myeloma (NDMM) patients with del(17p) in the novel-agent era, and to explore effective strategies to improve outcomes for this high-risk subgroup. MethodsA total of 97 NDMM patients with del(17p) admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between April 1, 2015 and December 31, 2025 were retrospectively enrolled. Baseline clinical features, del(17p) clonal fraction, concomitant high-risk cytogenetic abnormalities, treatment regimens and follow-up data were collected. According to the del(17p) cancer clonal fraction (CCF), patients were divided into 3 groups: low clonal burden group (CCF ≤20%), intermediate clonal burden group (20% < CCF < 50%), and high clonal burden group (CCF ≥50%). Based on whether 1q+ and t(4;14) were co-occurring, del(17p) was classified into 3 groups: isolated del(17p), double-hit group [del(17p) plus 1q+ or t(4;14)], and triple-hit group [del(17p) plus both 1q+ and t(4;14)]. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and survival differences across subgroups of varied CCF and cytogenetic profiles were compared by the log-rank test. Logistic regression models were applied to analyze factors associated with minimal residual disease (MRD) negativity. ResultsThe median age of the 97 patients was 63 (33–89) years; 31 patients (32%) were at revised International Staging System (R-ISS) stage Ⅲ, 36 patients (37%) received autologous hematopoietic stem cell transplantation (auto-HSCT), 43 patients (44%) received triple-drug induction consisting of proteasome inhibitor (PI), immunomodulatory drug (IMiD) and anti-CD38 monoclonal antibody (CD38Ab), and 37 patients (38%) achieved MRD-negative complete remission. Kaplan-Meier survival analysis showed that the 3-year PFS rates of low, intermediate and high clonal burden groups were 86%, 67% and 28%, respectively (P=0.015); the 3-year OS rates were 100%, 83% and 52%, respectively (P=0.045). The high clonal burden group had significantly lower PFS (P=0.010) and OS (P=0.024) than the low clonal burden group. The 3-year PFS rates in the isolated del(17p), double-hit, and triple-hit groups were 41%, 32%, and 0%, respectively, and the 3-year OS rates were 83%, 69%, and 16%, respectively. The triple-hit group had a median PFS of 2 months and median OS of 17 months, demonstrating markedly worse survival than the other two groups (all P<0.001). Among patients with del(17p), those who achieved MRD negativity had superior PFS [hazard ratio (HR)=0.388, P=0.003] and OS (HR=0.356, P=0.040). Multivariate analysis revealed that triple-drug induction and auto-HSCT were independent favorable factors for achieving MRD negativity (all P<0.05). ConclusionsIn the novel-agent era, del(17p) clonal burden may be associated with prognosis in NDMM patients. Co-occurrence of del(17p) with multiple high-risk cytogenetic abnormalities including 1q+ and t(4;14) is associated with a poorer prognosis. Triple-drug induction and auto-HSCT are associated with MRD negativity and may improve long-term prognosis of high-risk patients with del(17p).
ObjectiveTo discuss the impact of porphyra polysaccharide on osteoclast differentiation and healing of alveolar bone defects in osteoporotic mice. MethodsThe total sugar, protein content, molecular weight, and monosaccharide composition of porphyra polysaccharide were assessed. Cell counting kit-8 assay, real-time fluorescent quantitative polymerase chain reaction and tartrate-resistant acid phosphatase staining were used to evaluate the effects of porphyra polysaccharide on osteoclast differentiation of RAW 264.7 cells, and transcriptome sequencing was performed. Six-week-old female C57BL/6J mice were randomly assigned to sham surgery group, ovariectomy group, and ovariectomy + porphyra polysaccharide group. The mice in the ovariectomy and ovariectomy + porphyra polysaccharide groups underwent bilateral ovariectomy. Three months later, all three groups had their right maxillary incisors extracted to establish a bone defect model. The ovariectomy + porphyra polysaccharide group received porphyra polysaccharide 200 mg/(kg·d) through gastric gavage for 3 consecutive weeks, whereas the other 2 groups received 0.9% sodium chloride solution by gavage. Femurs were collected for Masson staining, enzyme-linked immunosorbent assay was used to detect bone metabolism indicators, and micro-CT was used to analyze the maxillary bone microstructure. ResultsPorphyra polysaccharide’s total sugar and protein contents were 67.54% and 2.9%, respectively, with a weight-average molecular weight of 270 kDa, and it was mainly composed of arabinose, xylose, galactose, and glucose. In cell experiments, porphyra polysaccharide significantly reduced the expression of osteoclast-related genes induced by receptor activator of nuclear factor κB ligand and the number of tartrate-resistant acid phosphatase-positive multinucleated osteoclasts (all P<0.01). Transcriptome analysis revealed that differentially expressed genes were enriched in tumor necrosis factor, interleukin-17, and mitogen-activated protein kinase signaling pathways. In animal experiments, compared with the sham surgery group, the ovariectomy group showed significantly reduced femoral bone volume fraction (0.199±0.013 vs. 0.378±0.016) and serum procollagen type Ⅰ N-terminal propeptide [(18.38±0.42) ng/mL vs. (20.66±0.39) ng/mL], and increased C-terminal telopeptide of type Ⅰ collagen [(1.41±0.02) ng/mL vs. (0.95±0.12) ng/mL] (all P<0.001). After intervention with porphyra polysaccharide, bone volume fraction (0.262±0.010) and N-terminal propeptide [(19.88±0.06) ng/mL] increased compared with the ovariectomy group, while C-terminal telopeptide [(1.21±0.04) ng/mL] decreased (all P < 0.001). Micro-CT of the maxilla revealed that bone volume fraction and number of trabecular bone in the porphyra polysaccharide group increased compared to the ovariectomy group, while the degree of separation decreased (all P < 0.05), but did not recover to the level of the sham surgery group. ConclusionsPorphyra polysaccharide can inhibit osteoclast differentiation and improve bone defect healing in osteoporotic mice.
