1.Low-dose ATG combined with low-dose PTCY in preventing GVHD after haploidentical transplantation:a retrospective analysis of 90 cases
Jinmei LEI ; Lin LIU ; Zhongtao YUAN ; Yu LI ; Le LUO ; Xiaoping LI ; Shiqi LI ; Sanbin WANG
Journal of Army Medical University 2024;46(4):326-330
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.
2.Control effect of Dasatinib on the treatment of acute myeloid leukemia and adverse events of CD123 targeting CAR-T:a case report and literature review
Chunmin LI ; Yu LI ; Zhongtao YUAN ; Lin LIU ; Le LUO ; Xiaoping LI ; Sanbin WANG ; Shiqi LI
Journal of Army Medical University 2024;46(4):347-351
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.
3.Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation
Yaqi ZHUO ; Sanfang TU ; Xuan ZHOU ; Jilong YANG ; Lijuan ZHOU ; Rui HUANG ; Yuxian HUANG ; Meifang LI ; Bo JIN ; Bo WANG ; Shiqi LI ; Zhongtao YUAN ; Lihua ZHANG ; Lin LIU ; Sanbin WANG ; Yuhua LI
Chinese Journal of Hematology 2024;45(1):74-81
Objective:To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People’s Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events.Results:A total of 81.82% ( n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546–1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% ( n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients ( n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion:Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.
4.Clinical study of the efficacies of ruxolitinib plus low-dose PTCY for acute GVHD prevention after haploidentical transplantation in malignant hematological diseases
Xiaoping LI ; Yu LI ; Lin LIU ; Zhongtao YUAN ; Youcheng WANG ; Yancheng DONG ; Dingsong ZHANG ; Jing FENG ; Yingnian CHEN ; Sanbin WANG
Chinese Journal of Hematology 2024;45(2):128-133
Objective:To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) .Methods:Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated.Results:A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% –20.5% ), respectively. Conclusion:Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.
5.Efficacy analysis of SEAM preconditioning regimen followed by autologous hematopoietic stem cell transplantation in relapsed/refractory non-Hodgkin lymphoma
Journal of Leukemia & Lymphoma 2021;30(7):395-399
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.
6.Clinical efficacy of low-dose decitabine and homoharringtonine combined with CAG regimen in treatment of acute myeloid leukemia
Lin LIU ; Xiaoli HUANG ; Sanbin WANG ; Le LUO ; Zhongtao YUAN
Journal of Leukemia & Lymphoma 2019;28(8):479-484
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.
7.Haploidentical hematopoietic stem-cell transplantation for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy
Kunyuan GUO ; Zhaoyang SONG ; Bingyi WU ; Yuhua LI ; Lan DENG ; Yi SU ; Jian CHEN ; Wenbin SAO ; Yi SUN ; Sanbin WANG ; Da LI ; Yuanbin WU ; Yongzhen HU ; Quanyi LU
Chinese Journal of Organ Transplantation 2011;32(3):141-143
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.
8.Retrospective analysis of the effectiveness of a pediatric protocol BFM90 in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia
Lihui PENG ; Dengming HU ; Sanbin WANG
Journal of Leukemia & Lymphoma 2010;19(6):331-333,337
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.
9.Allogeneic hematopoietic stem cell transplantation using Flu/CTX conditioning regimen for severe aplastic anemia
Sanbin WANG ; Dengming HU ; Lihui PENG ; Lin LIU ; Zhengjun XIE ; Bo YIN ; Xiaojuan SUN
Journal of Chinese Physician 2008;10(7):892-894
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.
10.Allogeneic hematopoietic stem cell transplantation using Flu/ivBu/TT conditioning regimen for refractory or relapsed acute non-lymphocytic leukemia
Sanbin WANG ; Dengming HU ; Lihui PENG ; Lin LIU ; Zhengjun XIE ; Bo YIN ; Xiaojuan SUN
Journal of Chinese Physician 2008;10(10):1300-1302
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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