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Objective To retrospectively analyze the efficacy and safety of low-dose antithymocyte globulin(ATG)combined with low-dose post transplantation cyclophosphamide(PTCY)in prevention of graft versus host disease(GVHD)after haploidentical transplantation.Methods Clinical data of 90 patients receiving haplotype matched transplantation in No.920 Hospital of PLA Joint Logistic Support Force from January 2022 to February 2023 were collected,and they were divided into study group(n=47)and control group(n=43)according to different GVHD prevention programs.The patients of the study group were given low-dose ATG combined with low-dose PTCY,and those of the control group received standard dose of PTCY.The implantation status,occurrence of GVHD,survival status and other indicators were analyzed between the 2 groups.Results ① Both groups of patients were successfully implanted,the median duration for neutrophil implantation(11 vs 17 d,P＜0.05)and platelet implantation(12 vs 20 d,P＜0.05)was significantly shorter in the study group than the control group.The incidence of grade Ⅱ～Ⅳ aGVHD(12.8％vs 34.9％,P＜0.05)and grade Ⅲ～Ⅳ aGVHD(6.4％ vs 20.9％,P＜0.05)was significantly lower in the study group than the control group,so was the non-recurrent mortality rate(6.4％vs 20.9％,P＜0.05)and the incidence of hemorrhagic cystitis(12.8％ vs 34.9％,P＜0.05).② By the end of the study,there were no significant differences in the incidence of mild and moderate and severe cGVHD,recurrence rate,reactivation rates of EBV and CMV,overall survival rate or progression-free survival rate between the 2 groups.Conclusion For haploidentical transplantation,low-dose ATG combined with low-dose PTCY has the advantages of lower incidence of GVHD,non-recurrent mortality,incidence of hemorrhagic cystitis and faster implantation.
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Objective To preliminarily explore the efficacy of chimeric antigen receptor T cells(CAR-T)targeting CD 123 in the treatment of acute myeloid leukemia(AML)and the role of dasatinib in the treatment of CD123 targeting CAR-T induced side effects.Methods Clinical data of 1 patient with relapsed AML admitted to No.920 Hospital of PLA Joint Logistic Support Force in September,2019 were collected.The patient relapsed after previous multi-line chemotherapy and was treated with CD123 targeting CAR-T therapy.The routine blood changes of the patient after treatment were observed.Dasatinib was used when agranulocytosis occurred,40 mg orally 3 times per day,and was stopped when agranulocytosis was relieved.Changes in blood cells,CAR-T amplification,and disease control were observed.The patient was followed up for over 1 year.Results Flow cytometry for bone marrow showed that minimal residual disease negative result was observed in 30 d after infusion.The patient remained disease-free for over 1 year.After CD 123 CAR-T cells infusion,significant expansion of CAR-T cells was observed,accompanied by granulocyte deficiency and cytokine release syndrome(CRS).After using dasatinib,inhibition of CAR-T cell expansion was observed,accompanied by blood cell recovery,and CRS symptoms were alleviated.After stop of dasatinib,CAR-T cells expanded again and blood cells decreased again.Conclusion CAR-T cells targeting CD 123 have certain efficacy in the treatment for relapsed AML.Dashatinib has a blocking effect on the amplification and function of CAR-T,which can alleviate bone marrow suppression caused by CD 123 targeting CAR-T and avoid severe CRS.
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CD19-targeted chimeric antigen receptor T lymphocytes (CAR-T) has demonstrated a high proportion of complete remission in the treatment of relapsed refractory acute B cell lymphoblastic leukemia (r/r B-ALL). It is of great clinical significance to explore which factors will impact long-term disease-free survival of patients with r/r B-ALL after CAR-T therapy without bridging bone marrow transplantation. Our study found that, in patients with r/r B-ALL without bridging transplantation, the patients' age; infusion dosage; whether they had undergone allo-stem cell transplantation before CAR-T therapy, using CD-19-targeted or CD19/CD22-dual-targeted CAR-T; whether there is fusion gene; tumor burden before therapy; and comorbidity had no significant relationship with their long-term disease-free survival. We found only that CAR-T persistence was highly correlated with patients' long-term disease-free survival. So, we further profiled CAR-T cells using single-cell sequencing and found that there is a specific T cell subset that may be associated with the long-term persistence of CAR-T. Finally, according to the single-cell sequencing results, we established cell production process named PrimeCAR, which shared common signaling pathways with the T cell subset identified. In the preliminary clinical study, prime CAR-Ts yield good persistence in peripheral blood of patients with B-ALL and lymphoma, without observing grade 2 or higher cytokine release syndrome.
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Objective To evaluate the efficacy and safety of low-dose decitabine and homoharringtonine combined with CAG regimen (cytarabine, aclarubicin and recombinant human granulocyte colony-stimulating factor) (DHCAG regimen) in treatment of acute myeloid leukemia (AML). Methods Nineteen patients who were treated with DHCAG regimen in the 920th Hospital of Joint Logistics Support Force from July 2017 to June 2018 were retrospectively analyzed. Among them, 13 cases were newly diagnosed, 6 cases were ineffective or relapsed; 2 cases were elderly (≥60 years old); 15 cases had pulmonary infection before chemotherapy, and 4 cases had no lesions in the lungs when admitted to hospital. The remission rate and chemotherapy-related adverse reactions were analyzed. Results After 19 patients received one course of DHCAG regimen, 16 patients had complete remission, 1 patient had partial remission, 2 patients had no remission, and the overall response rate was 89.5% (17/19). Four patients with undetected lung disease before chemotherapy had no infection in the lungs after treatment. Among 15 patients with pulmonary infection before treatment, 1 patient died of pulmonary infection progress, the remaining 14 cases were grade 1-2 infection. 7 cases had bleeding, and 3 cases had nausea and vomiting, all of which were grade 1-2. Conclusion The remission rate of DHCAG regimen in treatment of AML is high, and its adverse reactions are tolerable.
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Objective To explore the functions of neuron‐specific enolase(NSE) and human multiple myeloma U266 cells on osteoclast‐like cells(OLC) function .Methods Normal human peripheral blood mononuclear cells were induced and cultured by adding RANKL and M‐CSF to get OLC ;the experiment was divided into 3 groups ,the NSE group:OLC were cultured in the 6‐well culture plate for 14 d and added with 100 ng/mL recombinant human NSE to culture for 24 ,48 ,72 h;the co‐culture group:OLC were cultured in the lower well of 6‐well Transwell chamber for 14 d ,then added with 1 × 105/well U266 cells in each upper well and conducted the co‐culture for 24 ,48 ,72 h;the control group :OLC were cultured alone .The influences of NSE and U266 cell line on RANKL ,OPG ,IL‐6 and TRAP mRNA transcriptional level of OLS were compared by using real‐time fluorescent quantitative PCR .Results RANKL ,OPG ,IL‐6 mRNA had no expression on OLC in the co‐culture group ,NSE group and control group ;com‐pared with control group ,the TRAP mRNA expression level in the co‐culture group and the NSE group was increased ,the differ‐ence was statistically significant(P<0 .01);the increase of TRAP mRNA expression level was obvious especially at 48 ,72 h .Con‐clusion OLC expressing TRAP and NSE may be one of the factors for promoting OLC differentiation and maturation in myeloma bone disease ,prompting that NSE could increase the OLC viability .