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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 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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Objective:To investigate the efficacy and adverse effects of SEAM (semustine, etoposide, cytarabine and melphalan) preconditioning regimen followed by autologous hematopoietic stem cell transplantation (auto-HSCT) in treatment of patients with relapsed/refractory non-Hodgkin's lymphoma (NHL).Methods:The clinical data of 20 NHL patients receiveing conditioning regimen followed by auto-HSCT in 920th Hospital of PLA Joint Logistic Support Force from January 2015 to September 2020 were retrospectively analyzed. The pretreatment-related adverse effects, recovery of hematopoietic function after transplantation, and disease prognosis were observed.Results:During the pretreatment of 20 patients, 1 patient had pulmonary infection, 8 patients had nausea and vomiting, 3 patients had diarrhea, 1 patient had fever, 1 patient had lung injury, and 1 patient had mucositis. After auto-HSCT, 16 patients achieved hematopoietic reconstruction, the median time of neutrophil engraftment (neutrophil ≥0.5×10 9/L) was 13 d (8-30 d) and the median time of platelet engraftment (platelets ≥20×10 9/L) was 13 d (9-37 d). The median follow-up time was 27 months (3-65 months). Until the end of the follow-up, 16 (80%) patients had disease-free survival, 4 patients died, and no patient had recurrence and disease progression; non-relapse mortality was 20%. Conclusions:SEAM conditioning regimen followed by auto-HSCT has a better tolerance, less adverse events, quick recovery of hematopoietic reconstruction and good efficacy for NHL patients.
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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 investigate the therapeutic effects of haploidentical hematopoietic stem-cell transplantation (Haplo-PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy. Methods Eighty-nine cases of AML in first relapse after complete remission by standard DA/Hi-Ara-C regimens induction chemotherapy were evaluated retrospectively. Fiftythree cases were grafted by haplo-PBSCT and 26 cases were treated with iDA/Mid-Ara-C or MA/ Mid- Ara-C agents. Results The second remission rate in haplo-PBSCT group and continuous chemotherapy group was 86. 7 % (46/53 cases) and 38. 1% (9/23 cases) respectively (P＜0. 01). Survival postprogression (SPP) at 36th month was 43. 4 % (23/53 cases) in haplo-PBSCT group and 11.5 % (3/26 cases) in continuous chemotherapy group (P ＜ 0. 05). Conclusion Haplo-PBSCT could significantly increase the second remission rate and prolong the survival time of patients with acute myeloid leukernia in first relapse after complete remission by standard induction chemotherapy.
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Objective To retrospectively analyze the efficacy of a pediatric treatment protocol,BFM90,in adult patients with acute lymphobiastic leukemia (ALL) up to the age of 60 years. Methods From August 2004 to October 2007,60 adult patients (median age,40 years; range,18 to 60 years) with Philadelphia chromosome-negative ALL were treated with the BFM90 protocol. Clinical effect were historically compared with that of the 35 patients (median age,42 years; range,18 to 56 years) who were treated with Hyper-CVAD protocol. Results At 42 months,complete remission (CR) rate,event-free survival (EFS) and overall survival (OS) rates were 93 % (56 patients),60 % (36 patients) and 65 % (39 patients),respectively.Age is an important prognostic factor,with 45 years of age as best cutoff. CR (P=0.02),OS (P ＜0.001),and EFS (P ＜0.001) of BFM90 were compared superiorly with that of the previous Hyper-CVAD experience.Conclusion These results suggest that pediatric protocol superior to the outcome of adult patients with Philadelphia chromosome-negative ALL.
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Objective To evaluate the efficacy and feasibility of Flu/ivBu/Tl" conditioning regimen for the treatment of refractory or relapsed acute non-lymphocytic leukemia in patients receiving allogeneic hematopoietie stem cell transplantation. Methods Seven patients with refractory or relapsed acute non-lymphocytic leukemia received HLA identical peripheral blood hematopoietie stem cell transplantation (PBSCT) following Flu/ivBu/TY conditioning regimen, which consisted of fludarbine, busulfex and thiotepa. All patients received cyclos-porin A (CsA) and mycophenolet mofetil (MMF) for prophylaxis of graft - versus - host disease (GVHD). Results The Flu/IVBu/TT regimen was tolerated very well, without severe regimen related toxicity. In the 31-month median follow-up duration, 5 of 7 patients were a-live in disease-free situation. Conclusion The Flu/ivBu/TT conditioning regimen reduced transplantation-related toxicities and offered high long-term disease-free survival, and was tolerated very well. Allogeneie hematopoietie stem cell transplantation using Flu/ivBu/TT condition-ing regimen is a safe and effective option for the patients with refractory/relapsed acute non-lymphocytic leukemia.
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Objective To evaluate the efficacy of Flu/CTX conditioning regimen for the treatment of severe aplastic anemia in pa- tients receiving allogeneic hematopoietic stem cell transplantation. Methods Nine patients with severe aplastic anemia received HLA identi- cal peripheral blood hematopoietic stem cell transplantation (PBSCT) using Flu/CTX conditioning regimen, which consisted of fludarbine [30 mg/(m2 d) for5 days (-7 to -3) ], CTX [50mg/(kg d) for4 days(-5 to-2)]. All patients received cyclosporin A (CsA) and mycophenolet mofetil (MMF) for prophylaxis of graft-versus-host disease(GVHD). Results The Fiu/CTX regimen was very well toler- ated, with no severe regimen related toxicity. In all patients, the median days of neutrephil exceeding 0. 5×109/L and platelet exceeding 20 ×109/L were 12 days (range 10-16 days) and 16 days (range 14-19 days), respectively. Complete chimerism was achieved in all pa- tients at one month after PBSCT. Two patients had acute GVHD and one had chronic GVHD. In the 39-month median follow-up duration, all patients were alive in disease-free situation. Conclusion The Flu/CTX conditioning regimen may reduce transplantation-related toxicities and can achieve full chimerism and high long-term disease-free survival. Allogeneic hematopoietic stem cell transplantation using intravenous Fiu/CTX conditioning regimen is a safe and effective treatment method for the patients with severe aplastic anemia.
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20?109/L in 12 to 19(median 14)days after transplantation.Complete chimerism was achieved in all the patients at one month after HSCT.Two patients had acute GVHD and one had chronic GVHD.With a median follow-up of 31(19~37)months,8 of 9 patients were alive and disease-free.Conclusion The intravenous Bu/Flu conditioning regimen may reduce transplantation-related toxicities and can achieve full chimerism and high long-term disease-free survival.Allogeneic hematopoietic stem cell transplantation using intravenous Bu/Flu conditioning regimen is a safe and effective option for the patients with myeloid hematopathy.
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Objective To study the feasibility of HLA non-identical allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBHSCT) for the treatment of patients with severe aplastic anemia (SAA). Methods Four patients with SAA received non-identical allo-PBHSCT from HLA one or three loci mismatched related donors. Donors were given G-CSF 5?g/(kg?d) for 5 days, then PBSC were harvested on days 4 and 5. Prime regimen consisted of fludarbine, CTX, ATG and TBI. Combination of CsA, MTX, MMF and Simulect (CD25 monoclonal antibody) were used for GVHD prophylaxis. Results Engraft was achieved in all patients. The median days of neutrophil exceeding 0.5?109/L and platelet exceeding 20?109/L were 15.3 days (range 14~16 days) and 17.5 days (range 16~19 days), respectively. In the 14-month median follow-up duration, only one of four patients developed grade Ⅱ aGVHD, and one patient died of systemic candidiasis, the other three were alive in disease-free condition. Conclusion HLA non-identical allo-PBHSCT was well tolerated by patients with SAA, and it provided rapid and sustained engraftment without increase in incidence of GVHD.
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This study was undertaken to explore whether the graft-versus-host-disease could be decreased and graft-versus-leukemia effect be retained by transplantation of allogeneic T helper-2 (Th2) cells. T cells from C57BL/6(H-2b) mice were incubated and polarized with rmIL-4, Con A and ionomycin in vitro, and then, the T cells were mixed with marrow cells and transplanted into recipient BALB/c(H-2d) mice bearing erythroleukemia cells. The occurence of GVHD and GVL effect was observed. The results showed that the mean survival time in the groups of untreated control, cyclophosphamide treatment, marrow and spleen T cell transplantation and marrow and Th2 cell transplantation was 10.6 +/- 1.3, 18.7 +/- 4.2, 22.7 +/- 7.4 and 36.9 +/- 10.8 days, respectively. In untreated control and cycophosphamide treatment groups, all of ten mice died from leukemia. Nine of ten mice died from GVHD in marrow and spleen T cells transplantation group. In marrow and spleen Th2 cell transplantation group, three of ten mice died from GVHD, and GVHD was not occurred in the other seven mice, and there was no any evidence of leukemia in two mice on 50 days after transplantation. It was concluded that tranplantation with polarized Th2 cells could relieve GVHD, and at the same time retain the GVL effect.