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Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.
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Objective:To investigate the correlation between the lipocalin-2 (LCN-2) level and white matter hyperintensities (WMHs) in patients with ischemic stroke.Methods:Consecutive patients with ischemic stroke admitted to the Department of Neurology, Jinling Hospital, Medical School of Nanjing University from September 2021 to November 2021 and whose duration from onset to hospitalization <14 d were prospectively enrolled. Enzyme-linked immunosorbent assay was used to detect the serum LCN-2. Fazekas scale was used to assess the severity of periventricular and subcortical WMHs. A total WMHs score ≥3 was defined as severe WMHs. Multivariate logistic regression analysis was used to determine the correlation between serum LCN-2 level and WMHs. Results:A total of 179 patients were enrolled, including 122 males (68.2%), aged 64.7±11.6 years. The median serum LCN-2 level was 387.1 g/L, and 86 patients (48.0%) had severe WMHs. Serum LCN-2 in the severe WMH group was significantly higher than that in the non-severe WMH group (505.3±342.4 g/L vs. 367.8±224.5 g/L; t=3.110, P=0.002). Multivariable logistic regression analysis showed that after adjusting for the relevant confounding factors, there was a significant correlation between higher serum LCN-2 and severe WMHs (odds ratio 2.32, 95% confidence interval 1.17-4.63; P=0.017) and higher total WMHs score (odds ratio 1.62, 95% confidence interval 1.12-2.35; P=0.011). Conclusion:Higher serum LCN-2 level is associated with severe WMHs in patients with ischemic stroke.
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Objective:This study aims to examine the clinicopathological features, diagnosis, and treatment of pulmonary margin-al zone B-cell lymphoma of mucosa-associated lymphoid tissue (PMZL-MALT). Methods:The clinicopathological features and immu-nohistochemical staining of CD20, CD79a, CD5, CD10, CD23, CyclinD1, and Ki-67 in seven patients with PMZL-MALT were ana-lyzed. Results:These patients, with a median age of 58 years, included three males and four females. Most of the patients suffered from cough, anhelation, and irregular fever. No specific imaging manifestation was observed. Tumor cells were positive for CD19 and CD20 but negative for CD5, CD10, and CyclinD1. The positive rate of Ki-67 was low. Conclusion:PMZL-MALT cases are easily misdiag-nosed because of the absence of specific clinical characteristics and X-ray features. Final diagnosis depends on pathological examina-tions.
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Objective To investigate the distribution of TCR Vβ genealogy and clonal expansion in peripheral blood after infusing mesenchymal stem cells (MSC) in patients with chronic GVHD. Methods The complementarity determining region 3 (CDR3) of 24 TCR Vβ subfamily genes in peripheral blood mononuclear cell from 1 case with cGVHD after allogeneic hematopoietic stem cell transplantation (Allo-HSCT),who were treated with infusing MSC,were amplified using RT-PCR. The blood samples were taken at the first and the fifth day after 1st infusion; and the first day,the 10 th day and the 20 th day after the second infusion of MSC,as well as the MSC infused as control . The products were labelled by fluorescein and then analyzed the CDR3 size with gene scan technique to determine the clonality of T cells. Results There were no expression of TCR Vβ subfamily with the MSC infused and after the 1st day of the first infusion of MSC. Then 3,10,14,10 Vβ subfamilies clones are appeared at the other time points,of which were polyclone and oligoclone predominately. In the same time,the manifestations of cCVHD have been abated. Conclusion MSC played a certain role in reviving the immune function of the patients after Allo-HSCT and mitigating the disease of chronic GVHD. Lineage analysis of TCR Vβ subfamily showed some predominant expression.
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Objective To investigate the impact of auto and allogenic mesenchymal stem cells (MSC) transplantation on hematopoietic reconstitution. Methods MSC from auto, donor bone marrow or embryonic tissue were cultured and expanded in vitro in the serum culture system. Five patients received hematopoietic stem cell transplantation (HSCT) were investigated. Case 1 of systemic lupus erythematosus and Case 2 of non-hodgkin' s lymphoma (NHL) received auto MSC transplant before auto-HSCT. Case 3 of paroxysmal nocturnal hemoglobinuria received HLA-identical allogenic MSC transplant before HLA-identical allo-HSCT.Case 4 of chronic myelocytic leukemia and Case 5 of NHL had delayed hematopoietic reconstitution (129th and 78th day, respectively) after allo- and auto-HSCT, respectively, and received MSC from embryonic tissue.Results Case 1, 2 and 3 had no manifested side effects after MSC transplantation combined with HSCT.Neutrophil count of case 1, 2, and 3 were over 0.5 ×109/L at 1st, 10th and 10th day, respectively, platelet count were over 20 ×109/L at 1st, 8th and 33th day, respectively, and agranulocytosis at Ost, 7th and 12th day, respectively. The treatment of embryonic tissue MSC transplant was confirmed to fail for Case 4 and 5.Conclusion The time of MSC transplant has a great impact on hematopoietic reconstitution. MSC transplantation and HSCT performed simultaneously can improve hematopoietic reconstitution. However, the impact of MSC on patients with delayed hematopoietic reconstitution after HSCT needs further study.
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An HA-1-DC nucleic-acid vaccine was constructed to induce anti-leukemia effect after hematopoietic stem cell transplantation (HSCT). DCs were generated from HSCT donors in vitro, and its immunologic activity was assayed by using flow cytometry and mixed lymphocytes reaction.HA-1 gene was electroporated into the cultured DCs to construct a DC nucleic-acid vaccine. After transfection for 48 h, the expression of HA-1 protein could be detected by using Western blot. The DCs were cultured with syngenic lymphocytes to induce specific cytotoxic T lymphocytes (CTLs).The cytoxicity of the CTLs was detected by LDH assay. The results showed that The DCs derived from peripheral blood monocytes (PBMCs) expressed the phenotype of DCs, and were effective in stimulating proliferation of the allogenic lymphocytes. After electroporating for 48-h, HA-1 protein was detected by using Western blot. The cytotoxity of inducing CTLs was higher than the control group. It was suggested that minor histocompatibility antigen HA-1 could be considered as a target of immunotherapy against leukemia after HSCT.
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An HA-1-DC nucleic-acid vaccine was constructed to induce anti-leukemia effect after hematopoietic stem cell transplantation (HSCT). DCs were generated from HSCT donors in vitro, and its immunologic activity was assayed by using flow cytometry and mixed lymphocytes reaction. HA-1 gene was electroporated into the cultured DCs to construct a DC nucleic-acid vaccine. After transfection for 48 h, the expression of HA-1 protein could be detected by using Western blot. The DCs were cultured with syngenic lymphocytes to induce specific cytotoxic T lymphocytes (CTLs). The cytoxicity of the CTLs was detected by LDH assay. The results showed that The DCs derived from peripheral blood monocytes (PBMCs) expressed the phenotype of DCs, and were effective in stimulating proliferation of the allogenic lymphocytes. After electroporating for 48-h, HA-1 protein was detected by using Western blot. The cytotoxicty of inducing CTLs was higher than the control group. It was suggested that minor histocompatibility antigen HA-1 could be considered as a target of immunotherapy against leukemia after HSCT.
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Objective To evaluate the therapeutic effect of autologous hematopoietic stem cell transplantation(AHSCT)on hematological malignancies and solid tumors.Methods Twenty patients with age from 18 to 50 years received AHSCT.Two or 3 of following agents,Cytarabine(Ara-C)3～4 g/m2,Cyclophosphamide(CTX)4～6 g/m2,Etoposide(VP-16)0.5～1.0 g/m2,Semustine(me-CCNU)300 mg/m2,Melphalan(Mel)140 mg/m2,Thiotep a(TSPA)600 mg/m2,Carboplatin(CBP)1.0 g/m2,Busulfan 16mg/kg,were combined as conditioning regimen in all patients.Among them 2 patients with ALL accepted additional total body irradiation(TBI).Results All the patients have reconstituted bone marrow hematopoiesis after transplantation.None of them had the transplantation-related mortality.Among 20 patients with CML and malignant lymphoma,15 achieved disease-free survival(DFS)with a median survival time of 39.5(2～109)months.Conclusion AHSCT might represent an effective approach to the treatment of some patients with chemosensitive solid tumor who are complete remission or part remission.It is suggested that the patients have got a obvious survival benefit from AHSCT.