This paper described the therapeutic efficacy of immunosuppressive (IS) treatment agents (ATG and CSA) and androgens in the treatment of childhood aplastic anemia (AA). The results showed that the overall curative rat...This paper described the therapeutic efficacy of immunosuppressive (IS) treatment agents (ATG and CSA) and androgens in the treatment of childhood aplastic anemia (AA). The results showed that the overall curative rate was 52.4% in the ATG therapy group (21 cases) and 58.3% in the CSA therapy group (12 cases) respectively. The effective rate of all patients (SAA and CAA) was 58.1% in the IS group (18/31) and 40.4% in the androgens group (42/104), P】0.05. But, in the childhood patients with SAA, the clinical effective rate was 68.4% in the IS group and 7.9% in the androgens group, P【0.01. The laboratory tests revealed that the majority of the AA patients displalyed abnormal immunological states: inversed CD4/ CD8 ratio and increased IL-2 activity. These abnormal immunological states could be normalized in several patients when clinical response was abtained following IS therapy with ATG and CSA.展开更多
Given that randomized studies testing the long-term impact of antithymocyte globulin(ATG)dosing are scarce,we report the results of an extended follow-up from the original trial.In our prospective,multicenter,randomiz...Given that randomized studies testing the long-term impact of antithymocyte globulin(ATG)dosing are scarce,we report the results of an extended follow-up from the original trial.In our prospective,multicenter,randomized trial,408 leukemia patients 14–65 years of age who underwent haploidentical hematopoietic cell transplantation(haplo-HCT)under our original“Beijing Protocol”were randomly assigned one-to-one to ATG doses of 7.5 mg/kg(n=203,ATG-7.5)or 10 mg/kg(n=205,ATG-10.0)at four sites.Extended follow-up(median 1968 d(range:1300–2710 d)indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease(GVHD)(hazard ratio(HR):1.384,95%confidence interval(CI):0.876–2.189,P=0.164),nonrelapse mortality(HR:0.814,95%CI:0.526–1.261,P=0.357),relapse(HR:1.521,95%CI:0.919–2.518,P=0.103),disease-free survival(HR:1.074,95%CI:0.783–1.473,P=0.658),and GVHD-free/relapse-free survival(HR:1.186,95%CI:0.904–1.555,P=0.219)between groups(ATG-7.5 vs.ATG-10.0).The 5-year rate of late effects did not differ significantly.However,the cytomegalovirus/Epstein-Barr virus-related death rate was much higher in the ATG-10.0 cohort than in the ATG-7.5 cohort(9.8%vs.1.5%;P=0.003).In summary,patients undergoing haplo-HCT benefit from 7.5 mg/kg ATG compared to 10.0 mg/kg ATG based on a balance between GVHD and infection control.ATG(7.5 mg/kg)is potentially regarded as the standard regimen in the platform.These results support the optimization of ATG use in the“Beijing Protocol”,especially considering the potential economic advantage in developing countries.展开更多
Antithymocyte globulin （ATG） has long been used for immune-induction and anti-rejection treatments for solid organ transplantations. To date, few cases of ATG-induced acute respiratory distress syndrome （ARDS） hav...Antithymocyte globulin （ATG） has long been used for immune-induction and anti-rejection treatments for solid organ transplantations. To date, few cases of ATG-induced acute respiratory distress syndrome （ARDS） have been published. Here, we present a case of ARDS caused by a single low-dose of ATG in a renal transplant recipient and the subsequent treatments administered. Although the patient suffered from ARDS and delayed graft function, he was successfully treated. We emphasize that the presence of such complications should be considered when unexplained respiratory distress occurs. Early use of corticosteroids, adjustment of immunosuppressive regimens, and conservative fluid management, as well as empiric antimicrobial therapies, may be effective strategies for the treatment of ARDS caused by ATG.展开更多
This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation(haploHSCT)for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone M...This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation(haploHSCT)for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone Marrow Transplantation Registry Group(CBMTRG).For each PTCy,G-CSF/ATG subjects(1:4)were selected using the nested case-pair method.In total,220 patients including 176 in G-CSF/ATG group and 44 in PTCy group were analyzed.The incidences of 30-day neutrophil engraftment(88.6%vs.96.6%,P=0.001),90-day platelet engraftment(84.1%vs.94.2%,P=0.04),the median time to neutrophil engraftment(17 days vs.12 days,P=0.000)and platelet engraftment(22 days vs.17 days,P=0.001)were significantly inferior in PTCy group.The incidences of grades 2–4 and 3–4 acute graft-versus-host disease(GVHD),chronic GVHD and severe chronic GVHD were comparable.Among G-CSF/ATG and PTCy groups,the 3-year progression-free survival,overall survival,cumulative incidences of nonrelapse mortality and relapse was 74.3%vs.61%(P=0.045),78.3%vs.65.2%(P=0.039),12%vs.27.3%(P=0.008),and 14.9%vs.11.7%(P=0.61),respectively.G-CSF/ATG can achieve better engraftment,PFS and OS,and lower incidence of NRM compared to PTCy in myeloablative haplo-HSCT for hematologic malignancies.展开更多
Background Immunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody...Background Immunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.Methods In this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients （panel reactive antibody 〉20%）. They were divided into two groups： alemtuzumab group （trial group） and anti-thymocyte globulin （ATG） group （control group）. Patients in the alemtuzumab group received intravenous alemtuzumab （15 mg） as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab （15 mg） was given. The control group received a bolus of rabbit ATG （9 mg/kg）, which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil （MMF）. Acute rejection （AR） and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up. X2 test, ttest and Kaplan-Meier analysis were performed with SPSS17.0 software.Results Median follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar （P 〉0.05）. White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months （P 〈0.05）. One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group （P 〉0.05） respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group （P 〉0.05）.Conclusion Alemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.展开更多
文摘This paper described the therapeutic efficacy of immunosuppressive (IS) treatment agents (ATG and CSA) and androgens in the treatment of childhood aplastic anemia (AA). The results showed that the overall curative rate was 52.4% in the ATG therapy group (21 cases) and 58.3% in the CSA therapy group (12 cases) respectively. The effective rate of all patients (SAA and CAA) was 58.1% in the IS group (18/31) and 40.4% in the androgens group (42/104), P】0.05. But, in the childhood patients with SAA, the clinical effective rate was 68.4% in the IS group and 7.9% in the androgens group, P【0.01. The laboratory tests revealed that the majority of the AA patients displalyed abnormal immunological states: inversed CD4/ CD8 ratio and increased IL-2 activity. These abnormal immunological states could be normalized in several patients when clinical response was abtained following IS therapy with ATG and CSA.
基金supported by the National Key Research and Development Program of China(2019YFC0840606)from the Ministry of Science and Technologythe National Natural Science Foundation of China(82070189,81770189,81621001,and 81530046)+1 种基金the Science and Technology Project of Guangdong Province of China(2016B030230003)the Project of Health Collaborative Innovation of Guangzhou City(201704020214)。
文摘Given that randomized studies testing the long-term impact of antithymocyte globulin(ATG)dosing are scarce,we report the results of an extended follow-up from the original trial.In our prospective,multicenter,randomized trial,408 leukemia patients 14–65 years of age who underwent haploidentical hematopoietic cell transplantation(haplo-HCT)under our original“Beijing Protocol”were randomly assigned one-to-one to ATG doses of 7.5 mg/kg(n=203,ATG-7.5)or 10 mg/kg(n=205,ATG-10.0)at four sites.Extended follow-up(median 1968 d(range:1300–2710 d)indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease(GVHD)(hazard ratio(HR):1.384,95%confidence interval(CI):0.876–2.189,P=0.164),nonrelapse mortality(HR:0.814,95%CI:0.526–1.261,P=0.357),relapse(HR:1.521,95%CI:0.919–2.518,P=0.103),disease-free survival(HR:1.074,95%CI:0.783–1.473,P=0.658),and GVHD-free/relapse-free survival(HR:1.186,95%CI:0.904–1.555,P=0.219)between groups(ATG-7.5 vs.ATG-10.0).The 5-year rate of late effects did not differ significantly.However,the cytomegalovirus/Epstein-Barr virus-related death rate was much higher in the ATG-10.0 cohort than in the ATG-7.5 cohort(9.8%vs.1.5%;P=0.003).In summary,patients undergoing haplo-HCT benefit from 7.5 mg/kg ATG compared to 10.0 mg/kg ATG based on a balance between GVHD and infection control.ATG(7.5 mg/kg)is potentially regarded as the standard regimen in the platform.These results support the optimization of ATG use in the“Beijing Protocol”,especially considering the potential economic advantage in developing countries.
文摘Antithymocyte globulin （ATG） has long been used for immune-induction and anti-rejection treatments for solid organ transplantations. To date, few cases of ATG-induced acute respiratory distress syndrome （ARDS） have been published. Here, we present a case of ARDS caused by a single low-dose of ATG in a renal transplant recipient and the subsequent treatments administered. Although the patient suffered from ARDS and delayed graft function, he was successfully treated. We emphasize that the presence of such complications should be considered when unexplained respiratory distress occurs. Early use of corticosteroids, adjustment of immunosuppressive regimens, and conservative fluid management, as well as empiric antimicrobial therapies, may be effective strategies for the treatment of ARDS caused by ATG.
基金This work was supported by the National Natural Science Foundation of China(81670167)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)sponsored by the Fund for Fostering Young Scholars of Peking University Health Science Center(BMU2017PY010)。
文摘This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation(haploHSCT)for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone Marrow Transplantation Registry Group(CBMTRG).For each PTCy,G-CSF/ATG subjects(1:4)were selected using the nested case-pair method.In total,220 patients including 176 in G-CSF/ATG group and 44 in PTCy group were analyzed.The incidences of 30-day neutrophil engraftment(88.6%vs.96.6%,P=0.001),90-day platelet engraftment(84.1%vs.94.2%,P=0.04),the median time to neutrophil engraftment(17 days vs.12 days,P=0.000)and platelet engraftment(22 days vs.17 days,P=0.001)were significantly inferior in PTCy group.The incidences of grades 2–4 and 3–4 acute graft-versus-host disease(GVHD),chronic GVHD and severe chronic GVHD were comparable.Among G-CSF/ATG and PTCy groups,the 3-year progression-free survival,overall survival,cumulative incidences of nonrelapse mortality and relapse was 74.3%vs.61%(P=0.045),78.3%vs.65.2%(P=0.039),12%vs.27.3%(P=0.008),and 14.9%vs.11.7%(P=0.61),respectively.G-CSF/ATG can achieve better engraftment,PFS and OS,and lower incidence of NRM compared to PTCy in myeloablative haplo-HSCT for hematologic malignancies.
文摘Background Immunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.Methods In this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients （panel reactive antibody 〉20%）. They were divided into two groups： alemtuzumab group （trial group） and anti-thymocyte globulin （ATG） group （control group）. Patients in the alemtuzumab group received intravenous alemtuzumab （15 mg） as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab （15 mg） was given. The control group received a bolus of rabbit ATG （9 mg/kg）, which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil （MMF）. Acute rejection （AR） and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up. X2 test, ttest and Kaplan-Meier analysis were performed with SPSS17.0 software.Results Median follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar （P 〉0.05）. White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months （P 〈0.05）. One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group （P 〉0.05） respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group （P 〉0.05）.Conclusion Alemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.
