Anti-thymocyte globulin(ATG)is a pivotal immunosuppressive therapy utilized in the management of T-cell-mediated rejection and steroid-resistant rejection among renal transplant recipients.Commercially available as Th...Anti-thymocyte globulin(ATG)is a pivotal immunosuppressive therapy utilized in the management of T-cell-mediated rejection and steroid-resistant rejection among renal transplant recipients.Commercially available as Thymoglobulin(rabbit-derived,Sanofi,United States),ATG-Fresenius S(rabbit-derived),and ATGAM(equine-derived,Pfizer,United States),these formulations share a common mechanism of action centered on their interaction with cell surface markers of immune cells,imparting immunosuppressive effects.Although the prevailing mechanism predominantly involves T-cell depletion via the complement-mediated pathway,alternate mechanisms have been elucidated.Optimal dosing and treatment duration of ATG have exhibited variance across randomised trials and clinical reports,rendering the establishment of standardized guidelines a challenge.The spectrum of risks associated with ATG administration spans from transient adverse effects such as fever,chills,and skin rash in the acute phase to long-term concerns related to immunosuppression,including susceptibility to infections and malignancies.This comprehensive review aims to provide a thorough exploration of the current understanding of ATG,encompassing its mechanism of action,clinical utility in the treatment of acute renal graft rejections,specifically steroid-resistant cases,efficacy in rejection episode reversal,and a synthesis of findings from different eras of maintenance immunosuppression.Additionally,it delves into the adverse effects associated with ATG therapy and its impact on long-term graft function.Furthermore,the review underscores the existing gaps in evidence,particularly in the context of the Banff classification of rejections,and highlights the challenges faced by clinicians when navigating the available literature to strike the optimal balance between the risks and benefits of ATG utilization in renal transplantation.展开更多
Rabbit anti-thymocyte globulin's manifold mechanisms of action may be attribuited to its polyclonal nature. Its T-cell depleting effect on lymphoid cells is well established: Occurring in the blood and secondary l...Rabbit anti-thymocyte globulin's manifold mechanisms of action may be attribuited to its polyclonal nature. Its T-cell depleting effect on lymphoid cells is well established: Occurring in the blood and secondary lymphoid tissues, depletion proceeds through complement-dependent lysis, opsonization and apoptotic pathways. Clinical studies have shown that rabbit antithymocyte globulin's immunomodulatory effect extends beyond the initial T-cell depletion and up to the period during which lymphocyte populations begin to recover. The drug is able to mediate immunomodulation and graft tolerance by functionally inactivating cell surface receptors involved in antigen recognition, leukocyte trafficking and leukocyte endothelium adhesion. The complex and prolonged immunomodulation induced by this drug contributes to its efficacy in solid organ transplantation, mainly by reducing the incidence of acute graft rejection.展开更多
Children with severe aplastic anemia(SAA)face heterogeneous prognoses after immunosuppressive therapy(IST).There are few models that can predict the long-term outcomes of IST for these patients.The objective of this p...Children with severe aplastic anemia(SAA)face heterogeneous prognoses after immunosuppressive therapy(IST).There are few models that can predict the long-term outcomes of IST for these patients.The objective of this paper is to develop a more effective prediction model for SAA prognosis based on clinical electronic medical records from 203 children with newly diagnosed SAA.In the early stage,a novel model for long-term outcomes of SAA patients with IST was developed using machine-learning techniques.Among the indicators related to long-term efficacy,white blood cell count,lymphocyte count,absolute reticulocyte count,lymphocyte ratio in bone-marrow smears,C-reactive protein,and the level of IL-6,IL-8 and vitamin B12 in the early stage are strongly correlated with long-term efficacy(P<.05).Taken together,we analyzed the long-term outcomes of rabbit antithymocyte globulin and cyclosporine therapy for children with SAA through machine-learning techniques,which may shorten the observation period of therapeutic effects and reduce treatment costs and time.展开更多
Background Induction therapy are utilized to achieve an adequate immunosuppression at the time of transplantation. The use of basiliximab or anti-thymocyte globulin （ATG） for induction therapy has significantly redu...Background Induction therapy are utilized to achieve an adequate immunosuppression at the time of transplantation. The use of basiliximab or anti-thymocyte globulin （ATG） for induction therapy has significantly reduced the incidence of acute rejection episodes post-transplantation. The purpose of this study was to compare the efficacy and safety of the basiliximab in patients with immuno-induction therapy after kidney transplantation with the ATG. Methods A retrospective analysis was carried out in kidney transplant recipients including 146 patients with the basiliximab and 116 cases with the ATG and the acute rejection, graft function, infective complications and 1-year and 5-year actuarial patient and graft survival after renal transplantation were compared between the two treatment groups. Results There were no statistically significant difference between groups regarding age, sex, cold ischemic time, warm ischemic time, human leukocyte antigen （HLA） matching type between the donor and recipient, lymphotoxin test and the use of immunosuppressive agents. There was no statistical significance regarding the incidence of the acute rejection （9.59% vs. 8.62%, P=0.481） and delayed graft function （10.27% vs. 9.48%, P=0.501） between groups. There were significantly lower lung infection incidence （5.48% vs. 12.93%, P=0.029） in the basiliximab-treated group in comparison with the ATG-treated group. One-year patient and graft survival rates were 98%, 97% for the basiliximab-treated group, and 95%, 73% for the ATG-treated group, respectively. Five-year patient and graft survival rates were 92%, 86% for the basiliximab-treated group and 93%, 72% for the ATG-treated group, respectively. Log rank test showed statistically significant difference with P=0.038 for patients and P=-0.033 for grafts, respectively. There were significantly lower the incidence of granulocytopenia （8.22% vs. 17.24%, P=0.022） and thrombocytopenia （4.11% vs. 19.83%, P=0.000） after transplantation in the basiliximab-treated group in comparison with the ATG-treated group. There was no statistical significance regarding the incidence of the heart dysfunction after transplantation between the two groups （6.16% vs. 6.90%, P=0.502）. Conclusion The immuno-induction therapy with the basiliximab in kidney transplant recipients is efficient and safe with less complication compared with the ATG.展开更多
Objective： To explore the prognostic factors for very severe aplastic anemia （VSAA） patients treated mainly with Chinese Kidney （Shen）-invigorating drugs （CKID） combined with anti-lymphocyte globulin （ALG） or...Objective： To explore the prognostic factors for very severe aplastic anemia （VSAA） patients treated mainly with Chinese Kidney （Shen）-invigorating drugs （CKID） combined with anti-lymphocyte globulin （ALG） or anti-thymocyte globulin （ATG）. Methods： Twenty-seven VSAh. patients were treated with CSID＋ALG/ ATG therapy in conjunction with cyclosporine A, androgen, hemopoietic growth factor, etc. The relationship of the effectiveness and some factors （age of patients, course of illness, blood and bone marrow figures, etc.） were analyzed. Results： In the 25 evaluated VSAA patients who had been followed up for over 1 year, 9 patients （36.0%） were basically cured, 5 （20.0%） remitted, 6 （24.0%） were markedly improved, and 5 （20.0%） were treated in vain, with the total effective rate of treatment being 80.0% （20/25）. Better clinical therapeutic effects were shown in patients newly diagnosed with VSAA, of male sex （P=0.037）, 〉20 years old （P=0.045）, with an illness course ≤ 1 month （,P=0.048）, with peripheral neutrophil count 〉0.1 × 10^9/L （P=0.023）, and with reticulocyte count 〉10 × 10^9/L （P=0.002）. Platelet count （P=0.620） and bone marrow lymphocyte percentage （P=0.736） showed no correlation with the therapeutic effectiveness. Multi-factor analysis by the Kaplan-Meier procedure on the factors influencing survival showed that rather longer survival times occurred in patients 〉 20 years old, with peripheral neutrophil count ≤〈0.1 × 10^9/L, reticulocyte count ≤10 × 10^9/L, and platelet count 〉 10 × 10^9/L （allP=0.0001）. Bone marrow lymphocyte percentage and the initiation time of ALG/ATG application （from onset of the illness） showed no significant influence on patients＇ survival time （P=0.085 and P=0.935, respectively）. Conclusions： CSKD＋ALG/ATG therapy for treatment of VSAA could enhance the current clinical therapeutic effects and elevate patients＇ survival rate. Conditions including male sex, age 〉20 years, illness course ≤1 month, neutrophil count 〉0.1× 10^9/L, and reticulocyte count 〉10 × 10^9/L are the likely effective indices for predicting favorable therapeutic effectiveness in newly diagnosed VSAA patients.展开更多
Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vit...Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vitro T-cell depletion,have been adopted for haplo-HSCT in patients with SAA.The first is referred to as the"Beijing protocol"(Xu et al.,2017),and comprises a conditioning regimen using busulfex(BU),cyclophosphamide(CY).展开更多
Chronic graft-versus-host disease(cGVHD)is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We aimed to identify the risk factors for cGVHD in patients wh...Chronic graft-versus-host disease(cGVHD)is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia(n=280).The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria.A total of 169 patients suffered from cGVHD.The patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD(total,66.0%vs.53.7%,P=0.031;moderate to severe,42.4%vs.30.1%,P=0.036)than the patients who had 1 to 2 loci mismatched.The patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD(49.2%vs.32.9%,P=0.024)compared with the patients who had other donors.The patients who had grades III to IV acute GVHD(aGVHD)had higher 8-year incidence of cGVHD(total,88.0%vs.50.4%,P<0.001;moderate to severe,68.0%vs.27.0%,P<0.001)compared with the patients without aGVHD.In multivariate analysis,grades III to IV aGVHD was the only independent risk factor for cGVHD.Thus,further interventions should be considered in patients with severe aGVHD to prevent cGVHD.展开更多
Hemophagocytic lymphohistiocytosis(HLH) is a hyperinflammatory syndrome that develops as a primary(familial/hereditary) or secondary(non-familial/hereditary) disease characterized in the majority of the cases by hered...Hemophagocytic lymphohistiocytosis(HLH) is a hyperinflammatory syndrome that develops as a primary(familial/hereditary) or secondary(non-familial/hereditary) disease characterized in the majority of the cases by hereditary or acquired impaired cytotoxic T-cell(CTL) and natural killer responses. The molecular mechanisms underlying impaired immune homeostasis have been clarified, particularly for primary diseases. Familial HLH(familial hemophagocytic lymphohistiocytosis type 2-5, Chediak-Higashi syndrome, Griscelli syndrome type 2, Hermansky-Pudlak syndrome type 2) develops due to a defect in lytic granule exocytosis, impairment of(signaling lymphocytic activation molecule)-associated protein, which plays a key role in CTL activity [e.g., X-linked lymphoproliferative syndrome(XLP) 1], or impairment of X-linked inhibitor of apoptosis, a potent regulator of lymphocyte homeostasis(e.g., XLP2). The development of primary HLH is often triggered by infections, but not in all. Secondary HLH develops in association with infection, autoimmune diseases/rheumatological conditions and malignancy. The molecular mechanisms involved in secondary HLH cases remain unknown and the pathophysiology is not the same as primary HLH. For either primary or secondary HLH cases, immunosuppressive therapy should be given to control the hypercytokinemia with steroids, cyclosporine A, or intravenous immune globulin, and if primary HLH is diagnosed, immunochemotherapy with a regimen containing etoposide or anti-thymocyte globulin should be started. Thereafter, allogeneic hematopoietic stem-cell transplantation is recommended for primary HLH or secondary refractory disease(especially EBVHLH).展开更多
AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. METHODS: A monocentric, retrospective review of outcomes ...AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant(SKPT) and solitary pancreas transplant(SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with my-cophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide. RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186(92%) were primary and 16(8%) pancreas retransplants; portalenteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American(AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels 】 2.0 ng/m L. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit antithymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient(86% SKPT vs 87% SPT) and kidney(74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates(both 65%) were similar(P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively(P 【 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients(P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a “type 2 diabetes” phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels.CONCLUSION: In the new millennium, acceptablemedium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.展开更多
Epstein-Barr virus(EBV)reactivation is one of the most important infections after hematopoietic stem cell transplantation(HSCT)using haplo-identical related donors(HID).We aimed to establish a comprehensive model with...Epstein-Barr virus(EBV)reactivation is one of the most important infections after hematopoietic stem cell transplantation(HSCT)using haplo-identical related donors(HID).We aimed to establish a comprehensive model with machine learning,which could predict EBV reactivation after HID HSCT with anti-thymocyte globulin(ATG)for graft-versus-host disease(GVHD)prophylaxis.We enrolled 470 consecutive acute leukemia patients,60%of them(n=282)randomly selected as a training cohort,the remaining 40%(n=188)as a validation cohort.The equation was as follows:Probability(EBV reactivation)=1/1+exp(−Y),where Y=0.0250×(age)–0.3614×(gender)+0.0668×(underlying disease)–0.6297×(disease status before HSCT)–0.0726×(disease risk index)–0.0118×(hematopoietic cell transplantation-specific comorbidity index[HCT-CI]score)+1.2037×(human leukocyte antigen disparity)+0.5347×(EBV serostatus)+0.1605×(conditioning regimen)–0.2270×(donor/recipient gender matched)+0.2304×(donor/recipient relation)–0.0170×(mononuclear cell counts in graft)+0.0395×(CD34+cell count in graft)–2.4510.The threshold of probability was 0.4623,which separated patients into low-and high-risk groups.The 1-year cumulative incidence of EBV reactivation in the low-and high-risk groups was 11.0%versus 24.5%(P<.001),10.7%versus 19.3%(P=.046),and 11.4%versus 31.6%(P=.001),respectively,in total,training and validation cohorts.The model could also predict relapse and survival after HID HSCT.We established a comprehensive model that could predict EBV reactivation in HID HSCT recipients using ATG for GVHD prophylaxis.展开更多
OBJECTIVE： To explore the effect of antithymocyte globulin （ATG）/antilymphocyte globulin （ALG） plus kidney-nourishing Chinese medicinal （KNCM） on se- vere aplastic anemia （SAA）. METHODS： Twenty-five subjects...OBJECTIVE： To explore the effect of antithymocyte globulin （ATG）/antilymphocyte globulin （ALG） plus kidney-nourishing Chinese medicinal （KNCM） on se- vere aplastic anemia （SAA）. METHODS： Twenty-five subjects of severe aplastic anemia were treated with ATG/ALD plus KNCM be- tween 1992 and 2009, and the clinical data before and after treatment were collected and analyzed. RESULTS： Of the 25 patients, 9 were nearly cured, 6 were improved, 5 were in remission, and 5 failed. The overall effective rate was 80.0%. The 3-year, 5-year, 10-year, 15-year survival rate were respec- tively 98.6%, 97.3%, 97.3%, 67.5%, and median sur- vival time was 180 months. Compared to the condi- tions before administering the medication of ATG/ ALG plus KNCM, after 2 weeks, reticulocyte was first improved （P=0.001）, one month later, followed by palette （P=0.037）, two months later, by neutrophil cell in peripheral blood （P=0.001）; three months lat- er, then by the hemoglobin （P=0.012）. By conduct- ing 1-year follow-up, 1 case of complication--parox-ysmal nocturnal hemoglobinuria （PNH） was identi- fied and the patient still alive today. CONCLUSION： ATG/ALG fect on SAA and could rate. plus KNCM had better ef- improve patients＇ survival展开更多
Type 1 diabetes （T1D） is an insulin-dependent diabetes because of insufficient insulin production by the pancreatic islet 15 cells. Although the patnogemc mechanism of T1D is not yet completely clear, the current vi...Type 1 diabetes （T1D） is an insulin-dependent diabetes because of insufficient insulin production by the pancreatic islet 15 cells. Although the patnogemc mechanism of T1D is not yet completely clear, the current view of T1D pathogenesis is that under certain genetic background, exogenous or endogenous factors trigger autoimmunity against islet β cells in the pancreas causing β cell damage and subsequent insufficiency of insulin production. About two decades ago, it was first demonstrated that T cells specific ~o 15 cell antigens were activated and participated in the pathogenesis of T I D.3＇4 A great deal of work following these reports in both animal models and humans has provided convincing data further supporting T1D is a T cell-mediated autoimmune disease.展开更多
文摘Anti-thymocyte globulin(ATG)is a pivotal immunosuppressive therapy utilized in the management of T-cell-mediated rejection and steroid-resistant rejection among renal transplant recipients.Commercially available as Thymoglobulin(rabbit-derived,Sanofi,United States),ATG-Fresenius S(rabbit-derived),and ATGAM(equine-derived,Pfizer,United States),these formulations share a common mechanism of action centered on their interaction with cell surface markers of immune cells,imparting immunosuppressive effects.Although the prevailing mechanism predominantly involves T-cell depletion via the complement-mediated pathway,alternate mechanisms have been elucidated.Optimal dosing and treatment duration of ATG have exhibited variance across randomised trials and clinical reports,rendering the establishment of standardized guidelines a challenge.The spectrum of risks associated with ATG administration spans from transient adverse effects such as fever,chills,and skin rash in the acute phase to long-term concerns related to immunosuppression,including susceptibility to infections and malignancies.This comprehensive review aims to provide a thorough exploration of the current understanding of ATG,encompassing its mechanism of action,clinical utility in the treatment of acute renal graft rejections,specifically steroid-resistant cases,efficacy in rejection episode reversal,and a synthesis of findings from different eras of maintenance immunosuppression.Additionally,it delves into the adverse effects associated with ATG therapy and its impact on long-term graft function.Furthermore,the review underscores the existing gaps in evidence,particularly in the context of the Banff classification of rejections,and highlights the challenges faced by clinicians when navigating the available literature to strike the optimal balance between the risks and benefits of ATG utilization in renal transplantation.
文摘Rabbit anti-thymocyte globulin's manifold mechanisms of action may be attribuited to its polyclonal nature. Its T-cell depleting effect on lymphoid cells is well established: Occurring in the blood and secondary lymphoid tissues, depletion proceeds through complement-dependent lysis, opsonization and apoptotic pathways. Clinical studies have shown that rabbit antithymocyte globulin's immunomodulatory effect extends beyond the initial T-cell depletion and up to the period during which lymphocyte populations begin to recover. The drug is able to mediate immunomodulation and graft tolerance by functionally inactivating cell surface receptors involved in antigen recognition, leukocyte trafficking and leukocyte endothelium adhesion. The complex and prolonged immunomodulation induced by this drug contributes to its efficacy in solid organ transplantation, mainly by reducing the incidence of acute graft rejection.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS,2021-I2M-C&T-B-082)National Key Research and Development Program of China(2016YFC0901503)the National Natural Science Foundation of China(81500156,81170470).
文摘Children with severe aplastic anemia(SAA)face heterogeneous prognoses after immunosuppressive therapy(IST).There are few models that can predict the long-term outcomes of IST for these patients.The objective of this paper is to develop a more effective prediction model for SAA prognosis based on clinical electronic medical records from 203 children with newly diagnosed SAA.In the early stage,a novel model for long-term outcomes of SAA patients with IST was developed using machine-learning techniques.Among the indicators related to long-term efficacy,white blood cell count,lymphocyte count,absolute reticulocyte count,lymphocyte ratio in bone-marrow smears,C-reactive protein,and the level of IL-6,IL-8 and vitamin B12 in the early stage are strongly correlated with long-term efficacy(P<.05).Taken together,we analyzed the long-term outcomes of rabbit antithymocyte globulin and cyclosporine therapy for children with SAA through machine-learning techniques,which may shorten the observation period of therapeutic effects and reduce treatment costs and time.
文摘Background Induction therapy are utilized to achieve an adequate immunosuppression at the time of transplantation. The use of basiliximab or anti-thymocyte globulin （ATG） for induction therapy has significantly reduced the incidence of acute rejection episodes post-transplantation. The purpose of this study was to compare the efficacy and safety of the basiliximab in patients with immuno-induction therapy after kidney transplantation with the ATG. Methods A retrospective analysis was carried out in kidney transplant recipients including 146 patients with the basiliximab and 116 cases with the ATG and the acute rejection, graft function, infective complications and 1-year and 5-year actuarial patient and graft survival after renal transplantation were compared between the two treatment groups. Results There were no statistically significant difference between groups regarding age, sex, cold ischemic time, warm ischemic time, human leukocyte antigen （HLA） matching type between the donor and recipient, lymphotoxin test and the use of immunosuppressive agents. There was no statistical significance regarding the incidence of the acute rejection （9.59% vs. 8.62%, P=0.481） and delayed graft function （10.27% vs. 9.48%, P=0.501） between groups. There were significantly lower lung infection incidence （5.48% vs. 12.93%, P=0.029） in the basiliximab-treated group in comparison with the ATG-treated group. One-year patient and graft survival rates were 98%, 97% for the basiliximab-treated group, and 95%, 73% for the ATG-treated group, respectively. Five-year patient and graft survival rates were 92%, 86% for the basiliximab-treated group and 93%, 72% for the ATG-treated group, respectively. Log rank test showed statistically significant difference with P=0.038 for patients and P=-0.033 for grafts, respectively. There were significantly lower the incidence of granulocytopenia （8.22% vs. 17.24%, P=0.022） and thrombocytopenia （4.11% vs. 19.83%, P=0.000） after transplantation in the basiliximab-treated group in comparison with the ATG-treated group. There was no statistical significance regarding the incidence of the heart dysfunction after transplantation between the two groups （6.16% vs. 6.90%, P=0.502）. Conclusion The immuno-induction therapy with the basiliximab in kidney transplant recipients is efficient and safe with less complication compared with the ATG.
文摘Objective： To explore the prognostic factors for very severe aplastic anemia （VSAA） patients treated mainly with Chinese Kidney （Shen）-invigorating drugs （CKID） combined with anti-lymphocyte globulin （ALG） or anti-thymocyte globulin （ATG）. Methods： Twenty-seven VSAh. patients were treated with CSID＋ALG/ ATG therapy in conjunction with cyclosporine A, androgen, hemopoietic growth factor, etc. The relationship of the effectiveness and some factors （age of patients, course of illness, blood and bone marrow figures, etc.） were analyzed. Results： In the 25 evaluated VSAA patients who had been followed up for over 1 year, 9 patients （36.0%） were basically cured, 5 （20.0%） remitted, 6 （24.0%） were markedly improved, and 5 （20.0%） were treated in vain, with the total effective rate of treatment being 80.0% （20/25）. Better clinical therapeutic effects were shown in patients newly diagnosed with VSAA, of male sex （P=0.037）, 〉20 years old （P=0.045）, with an illness course ≤ 1 month （,P=0.048）, with peripheral neutrophil count 〉0.1 × 10^9/L （P=0.023）, and with reticulocyte count 〉10 × 10^9/L （P=0.002）. Platelet count （P=0.620） and bone marrow lymphocyte percentage （P=0.736） showed no correlation with the therapeutic effectiveness. Multi-factor analysis by the Kaplan-Meier procedure on the factors influencing survival showed that rather longer survival times occurred in patients 〉 20 years old, with peripheral neutrophil count ≤〈0.1 × 10^9/L, reticulocyte count ≤10 × 10^9/L, and platelet count 〉 10 × 10^9/L （allP=0.0001）. Bone marrow lymphocyte percentage and the initiation time of ALG/ATG application （from onset of the illness） showed no significant influence on patients＇ survival time （P=0.085 and P=0.935, respectively）. Conclusions： CSKD＋ALG/ATG therapy for treatment of VSAA could enhance the current clinical therapeutic effects and elevate patients＇ survival rate. Conditions including male sex, age 〉20 years, illness course ≤1 month, neutrophil count 〉0.1× 10^9/L, and reticulocyte count 〉10 × 10^9/L are the likely effective indices for predicting favorable therapeutic effectiveness in newly diagnosed VSAA patients.
文摘Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vitro T-cell depletion,have been adopted for haplo-HSCT in patients with SAA.The first is referred to as the"Beijing protocol"(Xu et al.,2017),and comprises a conditioning regimen using busulfex(BU),cyclophosphamide(CY).
文摘Chronic graft-versus-host disease(cGVHD)is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia(n=280).The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria.A total of 169 patients suffered from cGVHD.The patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD(total,66.0%vs.53.7%,P=0.031;moderate to severe,42.4%vs.30.1%,P=0.036)than the patients who had 1 to 2 loci mismatched.The patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD(49.2%vs.32.9%,P=0.024)compared with the patients who had other donors.The patients who had grades III to IV acute GVHD(aGVHD)had higher 8-year incidence of cGVHD(total,88.0%vs.50.4%,P<0.001;moderate to severe,68.0%vs.27.0%,P<0.001)compared with the patients without aGVHD.In multivariate analysis,grades III to IV aGVHD was the only independent risk factor for cGVHD.Thus,further interventions should be considered in patients with severe aGVHD to prevent cGVHD.
文摘Hemophagocytic lymphohistiocytosis(HLH) is a hyperinflammatory syndrome that develops as a primary(familial/hereditary) or secondary(non-familial/hereditary) disease characterized in the majority of the cases by hereditary or acquired impaired cytotoxic T-cell(CTL) and natural killer responses. The molecular mechanisms underlying impaired immune homeostasis have been clarified, particularly for primary diseases. Familial HLH(familial hemophagocytic lymphohistiocytosis type 2-5, Chediak-Higashi syndrome, Griscelli syndrome type 2, Hermansky-Pudlak syndrome type 2) develops due to a defect in lytic granule exocytosis, impairment of(signaling lymphocytic activation molecule)-associated protein, which plays a key role in CTL activity [e.g., X-linked lymphoproliferative syndrome(XLP) 1], or impairment of X-linked inhibitor of apoptosis, a potent regulator of lymphocyte homeostasis(e.g., XLP2). The development of primary HLH is often triggered by infections, but not in all. Secondary HLH develops in association with infection, autoimmune diseases/rheumatological conditions and malignancy. The molecular mechanisms involved in secondary HLH cases remain unknown and the pathophysiology is not the same as primary HLH. For either primary or secondary HLH cases, immunosuppressive therapy should be given to control the hypercytokinemia with steroids, cyclosporine A, or intravenous immune globulin, and if primary HLH is diagnosed, immunochemotherapy with a regimen containing etoposide or anti-thymocyte globulin should be started. Thereafter, allogeneic hematopoietic stem-cell transplantation is recommended for primary HLH or secondary refractory disease(especially EBVHLH).
文摘AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant(SKPT) and solitary pancreas transplant(SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with my-cophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide. RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186(92%) were primary and 16(8%) pancreas retransplants; portalenteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American(AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels 】 2.0 ng/m L. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit antithymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient(86% SKPT vs 87% SPT) and kidney(74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates(both 65%) were similar(P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively(P 【 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients(P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a “type 2 diabetes” phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels.CONCLUSION: In the new millennium, acceptablemedium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.
基金the Program of the National Natural Science Foundation of China(grant number 82170208)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(grant number 81621001)+2 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(grant number 2019-I2M-5-034)the Key Program of the National Natural Science Foundation of China(grant number 81930004)the Fundamental Research Funds for the Central Universities,National Natural Science Foundation of China(No.62102008).
文摘Epstein-Barr virus(EBV)reactivation is one of the most important infections after hematopoietic stem cell transplantation(HSCT)using haplo-identical related donors(HID).We aimed to establish a comprehensive model with machine learning,which could predict EBV reactivation after HID HSCT with anti-thymocyte globulin(ATG)for graft-versus-host disease(GVHD)prophylaxis.We enrolled 470 consecutive acute leukemia patients,60%of them(n=282)randomly selected as a training cohort,the remaining 40%(n=188)as a validation cohort.The equation was as follows:Probability(EBV reactivation)=1/1+exp(−Y),where Y=0.0250×(age)–0.3614×(gender)+0.0668×(underlying disease)–0.6297×(disease status before HSCT)–0.0726×(disease risk index)–0.0118×(hematopoietic cell transplantation-specific comorbidity index[HCT-CI]score)+1.2037×(human leukocyte antigen disparity)+0.5347×(EBV serostatus)+0.1605×(conditioning regimen)–0.2270×(donor/recipient gender matched)+0.2304×(donor/recipient relation)–0.0170×(mononuclear cell counts in graft)+0.0395×(CD34+cell count in graft)–2.4510.The threshold of probability was 0.4623,which separated patients into low-and high-risk groups.The 1-year cumulative incidence of EBV reactivation in the low-and high-risk groups was 11.0%versus 24.5%(P<.001),10.7%versus 19.3%(P=.046),and 11.4%versus 31.6%(P=.001),respectively,in total,training and validation cohorts.The model could also predict relapse and survival after HID HSCT.We established a comprehensive model that could predict EBV reactivation in HID HSCT recipients using ATG for GVHD prophylaxis.
文摘OBJECTIVE： To explore the effect of antithymocyte globulin （ATG）/antilymphocyte globulin （ALG） plus kidney-nourishing Chinese medicinal （KNCM） on se- vere aplastic anemia （SAA）. METHODS： Twenty-five subjects of severe aplastic anemia were treated with ATG/ALD plus KNCM be- tween 1992 and 2009, and the clinical data before and after treatment were collected and analyzed. RESULTS： Of the 25 patients, 9 were nearly cured, 6 were improved, 5 were in remission, and 5 failed. The overall effective rate was 80.0%. The 3-year, 5-year, 10-year, 15-year survival rate were respec- tively 98.6%, 97.3%, 97.3%, 67.5%, and median sur- vival time was 180 months. Compared to the condi- tions before administering the medication of ATG/ ALG plus KNCM, after 2 weeks, reticulocyte was first improved （P=0.001）, one month later, followed by palette （P=0.037）, two months later, by neutrophil cell in peripheral blood （P=0.001）; three months lat- er, then by the hemoglobin （P=0.012）. By conduct- ing 1-year follow-up, 1 case of complication--parox-ysmal nocturnal hemoglobinuria （PNH） was identi- fied and the patient still alive today. CONCLUSION： ATG/ALG fect on SAA and could rate. plus KNCM had better ef- improve patients＇ survival
基金This Work was supported by grants from the National Natural Science Foundation of China （No. 81172854）, and NIH 1R21DK080216-01A2.
文摘Type 1 diabetes （T1D） is an insulin-dependent diabetes because of insufficient insulin production by the pancreatic islet 15 cells. Although the patnogemc mechanism of T1D is not yet completely clear, the current view of T1D pathogenesis is that under certain genetic background, exogenous or endogenous factors trigger autoimmunity against islet β cells in the pancreas causing β cell damage and subsequent insufficiency of insulin production. About two decades ago, it was first demonstrated that T cells specific ~o 15 cell antigens were activated and participated in the pathogenesis of T I D.3＇4 A great deal of work following these reports in both animal models and humans has provided convincing data further supporting T1D is a T cell-mediated autoimmune disease.
