Treatment of severe aplastic anemia and hematopoietic stem cell transplantation / 器官移植

Severe aplastic anemia (SAA) is a severe bone marrow failure syndrome caused by multiple causes, which is clinically manifested with severe anemia, infection and bleeding. The complex pathogenesis of SAA has not been fully understood. SAA is characterized with acute onset, severe disease condition and rapid progression. At present, with the in-depth study of SAA and the improvement of diagnosis and treatment, the therapeutic strategy for SAA has been evolved from classical immunosuppressive therapy based on antithymocyte globulin and cyclosporine to the application of thrombopoietin receptor agonist and combined treatment based on allogeneic hematopoietic stem cell transplantation, which may promote the reconstruction of hematopoietic function of SAA patients to varying degree and significantly improve survival and clinical prognosis, becoming the research hotspot of SAA treatment. In this article, new advances in the treatment of SAA at home and abroad were reviewed.

Successful treatment of acute leukemia by secondary transplantation after the first haploidentical hematopoietic stem cell transplantation failure / 器官移植

Objective To evaluate the feasibility of secondary transplantation for patients with acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation. Methods Two acute leukemia patients underwent the first haploidentical hematopoietic stem cell transplantation from two donors with thalassemia, and the number of collected CD34+ cells was 2.57×106/kg and 1.99×106/kg per donor, respectively. The first haploidentical hematopoietic stem cell transplantation failed. Secondary transplantation was performed from two non-thalassemia donors, and the number of collected CD34+ cells was 4.28×106/kg and 5.75×106/kg per donor, respectively. A reduced-intensity conditioning regimen consisting of fludarabine (Flu), busulfan (Bu) and antithymocyte globulin (ATG) was adopted for the secondary transplantation. Results For two recipients, the time of secondary transplantation of neutrophil and platelet was +12 d and +10 d, +10 d and +10 d, respectively. Up to the final follow-up (+1 062 d and +265 d after secondary transplantation), the primary diseases of both two recipients have been completely relieved without evident post-transplantation complications. Conclusions Secondary transplantation with reduced-intensity conditioning regimen may successfully treat acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation.

Expert consensus on perioperative nursing standards for pediatric kidney transplantation / 器官移植

Pediatric kidney transplant recipients differ from adult counterparts in primary disease, physiology, psychology, organ function and immune status and their perioperative treatment and nursing management are different from those of adult kidney transplantation. To standardize holistic perioperative nursing regimens for pediatric kidney transplantation, Surgery Nursing Committee of Shanghai Nursing Association organized national medical and nursing experts in the fields of transplantation to jointly draft "expert consensus on perioperative nursing standards for pediatric kidney transplantation " (abbreviated as "consensus"). After three rounds of online expert inquiry, all revised opinions were jointly discussed combined with literature evidence, and the expert consensus was finally reached. The highlights of perioperative treatment and nursing care for pediatric kidney transplantation were summarized and stated, including preoperative evaluation, preoperative and postoperative nursing care, which were of scientific and practical value.

Protein A immunoadsorption in the treatment of de novo DSA-mediated acute rejection after lung transplantation / 器官移植

Objective To investigate the treatment on de novo donor specific antibody (dnDSA) mediated acute rejection after lung transplantation. Methods Clinical data of 1 recipient with antibody-mediated rejection (AMR) early after lung transplantation was retrospectively analyzed. The process of diagnosis and treatment were assessed. Results The recipient underwent right lung transplantation due to systemic sclerosis-associated end-stage interstitial lung disease. Preoperatively, classⅠ panel reactive antibody (PRA) was positive (11%). No pretreatment was given before transplantation. Antithymocyte globulin induction therapy was delivered on the day of transplantation and postoperatively. The recipient was properly recovered early after transplantation. Chest tightness and shortness of breath occurred at postoperative 13 d, which were progressively worsened and rapidly progressed into type Ⅰ respiratory failure. Class Ⅰ PRA was increased to 58%, and dnDSA was observed at the loci of A24: 02. The mean fluorescence intensity (MFI) was 2 110. According to the guidelines of International Society for Heart and Lung Transplantation, the recipient was diagnosed as possible AMR. After comprehensive treatment including plasmapheresis, protein A immunoadsorption, glucocorticoid pulse, rituximab and immunoglobulin intravenous drip, the PRA and DSA levels were gradually decreased, and the MFI of DSA was 0 at postoperative 20 d. Clinical condition of the recipient was gradually improved. The dyspnea was healed, shortness of breath was eased, respiratory failure was treated, and pulmonary effusion was gradually absorbed. At postoperative 45 d, the recipient was discharged after full recovery. During 1-year follow-up, the recipient was physically stable and obtained normal quality of life. Class Ⅰ PRA was 5%, and class Ⅱ PRA was negative. No DSA was noted. Conclusions Based on traditional drug therapy, supplement of protein A immunoadsorption therapy may effectively eliminate DSA from the circulating blood of the recipient and mitigate the damage of target organs. Ideal short- and long-term prognosis may be achieved. Traditional drug therapy combined with immunoadsorption may yield ideal efficacy in treating AMR after lung transplantation.

Efficacy and safety of basiliximab and antithymocyte globulin in immune induction in kidney transplantation: a Meta-analysis / 器官移植

Objective To evaluate the efficacy and safety of basiliximab (BAS) and antithymocyte globulin (ATG) in immune induction therapy in kidney transplantation by systematic review and Meta-analysis. Methods Prospective randomized controlled clinical trials screening and comparing BAS and ATG in immune induction therapy in kidney transplantation were systematically searched from global databases, screened and compared. The quality of clinical trials was evaluated by Jadad scoring system and data extraction was performed. The effects of BAS and ATG on the incidence of acute rejection, survival rate of kidney allografts, survival rate of recipients, incidence of delayed graft function, infection, cytomegalovirus infection, malignant tumor, leukopenia and thrombocytopenia at 1 year after kidney transplantation were analyzed. Results A total of 10 clinical trials in English consisting of 1 721 kidney transplant recipients were searched, including 883 cases in the ATG group and 838 cases in the BAS group. No significant differences were observed in the incidence of acute rejection, survival rate of kidney allografts, survival rate of recipients, incidence of delayed graft function, infection, cytomegalovirus infection and thrombocytopenia at postoperative 1 year between the ATG and BAS groups (all P > 0.05). The incidence of malignant tumor and leukopenia at postoperative 1 year in the ATG group were significantly higher than those in the BAS group (both P < 0.05). Conclusions The use of ATG and BAS for immune induction therapy in kidney transplantation yield equivalent efficacy at postoperative 1 year, but BAS is safer than ATG. Clinical trials related to stratified analyses of immune risk are urgently required to achieve individualized precision treatment.

Pharmacokinetic study of anti-human T-cell porcine immunoglobulin combined with cyclosporine A immunosuppressive therapy in patients with severe aplastic anemia / 中华血液学杂志

Objective: To study the metabolic characteristics of anti-human T-cell porcine immunoglobulin (p-ATG) in patients with severe aplastic anemia (SAA) . Methods: For patients with SAA treated with p-ATG combined cyclosporine A (CsA) immunosuppressants between February 2017 and December 2017, the p-ATG dose was 20 mg·kg(-1)·d(-1) over 12 h of intravenous administration for 5 consecutive days. The blood concentration of p-ATG was detected by the three-antibody sandwich ELISA method, the pharmacokinetic analysis software was fitted, and the second-chamber model method was used to calculate the pharmacokinetic parameters and plot the pharmacokinetic curve. Adverse events were recorded and the hematologic reactions were determined at 6 months after treatment. Results: Sixteen patients with SAA treated with p-ATG were enrolled, including 8 females and 8 males, with a median age of 22 years (range, 12 to 49 years) and a median weight of 62.5 kg (range, 37.5 to 82.0 kg) . The pharmacokinetics of p-ATG could be evaluated in 14 cases. p-ATG is distributed in vivo as a two-chamber model, with an average drug concentration peak (T(max)) of (5.786±2.486) days, a peak concentration (C(max)) of (616±452) mg/L, and a half-life of (10.479±8.242) days. The area under the drug time curve (AUC) was (5.807±3.236) mg/L·d. Six months after treatment, 8 of 14 patients received a hematologic response; the AUC (0-t) of the effective group and ineffective groups was (7.50±3.26) mg/L·d vs (4.50±2.18) mg/L·d, and the C(max) was (627±476) mg/L vs (584±382) mg/L, respectively. Conclusion: The plasma concentration of p-ATG reached a peak after 5 days of continuous infusion, and then decreased slowly, with a half-life of 10.479 days, and the residual drug concentration was detected in the body 60 days after administration. A relationship between drug metabolism and efficacy and adverse reactions could not be determined.

Application progress of individualized immune induction therapy in kidney transplantation / 器官移植

The risk of early acute rejection after kidney transplantation is relatively high, which severely affects the quality of life of the recipients. In 2009, Kidney Disease: Improving Global Outcomes (KDIGO) recommended that immune inducers should be included in the immune-inducing regime before kidney transplantation, aiming to provide certain strength of immunosuppression during this critical phase and effectively reduce the incidence of acute rejection following kidney transplantation. At present, the selection, efficacy and safety of immune inducers remain controversial among transplantation centers around the world. In this article, clinical efficacy of monoclonal antibodies including interleukin-2 receptor antagonist, alemtuzumab, rituximab and polyclonal antibody antithymocyte globulin in immune induction therapy before kidney transplantation were compared and literature review was performed at home and abroad, aiming to provide reference for promoting the individualized selection of immune inducers for kidney transplantation and improving the quality of life of recipients.

Clinical application progress of immune induction regimen for kidney transplantation / 器官移植

With the development of immunosuppressants and optimization of immunosuppressive regimens, the survival rates of kidney transplant recipients and grafts have been significantly increased, whereas the incidence of acute rejection and delayed graft function have also been significantly reduced. However, the standard triple immunosuppressive regimen (calcineurin inhibitor+antimetabolite+glucocorticoid) still cannot effectively control the rejection of transplant kidney. Consequently, immune induction before transplantation has been proposed. Immune induction therapy may delay the application time and reduce the dosage of calcineurin inhibitor, lower the incidence of short-term acute rejection after operation, and improve the middle- and long-term prognosis of the recipients. In this article, research progresses on monoclonal antibody-based immune induction regimen, polyclonal antibody-based immune induction regimen and mesenchymal stem cell-based immune induction regime were investigated, aiming to provide reference for optimizing the immune induction regime for kidney transplantation.

Treatment progress of severe aplastic anemia / 器官移植

Severe aplastic anemia (SAA) is a rare type of bone marrow hematopoietic failure, which is associated with toxic T lymphocyte-based immune dysfunction, abnormal hematopoietic microenvironment and damage of hematopoietic stem cells in patients. SAA characterized by acute onset, rapid progression and high mortality rate, which requires rapid and stable recovery of the patients' hematopoietic function. In this article, the therapeutic progresses on immunosuppressive therapy (IST), sibling human leukocyte antigen (HLA)-matched allogenetic hematopoietic stem cell transplantation (allo-HSCT), replacement of donor hematopoietic stem cell transplantation and unrelated umbilical cord blood hematopoietic stem cell transplantation (UCBT) for SAA were reviewed.

Effect of different induction therapies on the clinical outcomes of ABO-incompatible living donor kidney transplantation recipients / 中华器官移植杂志

Objective To compare the clinical outcomes of low-dose rabbit antithymocyte globulin (rATG ) vs basiliximab as induction therapy in recipients of ABO-incompatible kidney transplantation (ABOi-KT) .Methods Retrospective analysis was conducted for e the clinical data of 40 ABOi-KT recipients between March 2017 and March 2019 .17 recipients of them received induction therapy with basiliximab (basiliximab group) while another 23 recipients received low-dose rATG (rATG group ,rATG 25 mg/d × 3 d) .During a median follow-up period of 282 days , the data of serum creatinine and eGFR at 1 week and 1 month ,graft survival rate and complication rate of two groups were compared .Results No significant difference existed in age ,gender ,dialytic modality/ duration , blood groups of recipients , HLA mis-match , blood group antibody titers , dose of rituximab ,blood groups of donors or donor age ( P > 0 .05 ) . The times of double filtration plasmapheresis in Basiliximab group were more (P< 0 .05) .No significant difference existed in serum creatinine and eGFR at 1 week or 1 month ( P > 0 .05 ) . No significant difference existed in graft survival rate . No significant difference existed in rate of acute rejection ,parvovirus B19 infection , urinary tract infection or hematoma .Conclusions Low-dose of rATG is as effective as basiliximab for ABOi-KT recipients .And rATG does not increase the rate of infection .

Application of low-dose ATG for GVHD prophylaxis in patients undergoing PBSCT aged over forty years old / 中华血液学杂志

Objective@#To explore the effectiveness of a novel GVHD prophylaxis regimen containing low-dose anti-T lymphocyte globulin (ATG) in patients undergoing peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors (MSD) given both the patients and donors were aged over forty years old.@*Methods@#From March 2013 to April 2017, 98 patients with hematologic malignancies were enrolled in the study. Standard GVHD prophylaxis consisted of the administration of cyclosporine A/tacrolimus and a short course of methotrexate. In ATG group, 43 patients received low-dose rabbit ATG (Sanofi, 1.5 mg/kg per day for 3 consecutive days) before PBSCT. A retrospective matched-pair analysis was performed and 55 matched controls were available. The therapeutic process and clinical outcome were retrospectively analyzed.@*Results@#①Neutrophil engraftment was achieved earlier in ATG group than the control one [13(11-17)d vs 14(12-24)d, P=0.001]. The time to platelet engraftment was similar between the two groups [14(11-43)d vs 15(11-42)d, P=0.071]. ②The cumulative incidence of aGVHD was significantly lower in ATG group [25.6% (95%CI 13.7%-39.3%) vs 49.1% (95%CI 35.2%-61.6%), P=0.018]. The incidences of grade Ⅱ-Ⅳ aGVHD [18.6% (95%CI 8.6%-31.5%) vs 23.6% (95%CI 13.4%-35.6%), P=0.509] and cGVHD [49.6% (95% CI 31.6%-65.3%) vs 56.4% (95% CI 41.4%-69.0%), P=0.221] were not significantly different between the two groups. ③The 1-year cumulative incidence of CMV viremia was similar between the two groups [21.1%(95%CI 10.3%-34.5%) vs 31.1% (95%CI 18.8%-44.2%), P=0.429]. ④The cumulative incidences of disease relapse [24.0%(95%CI 11.5%-38.9%) vs 24.0% (95% CI 12.1%-38.2%), P=0.608), non-relapse mortality [10.2% (95% CI 3.1%-22.1%) vs 21.6% (95% CI 9.4%-37.0%), P=0.411] and DFS [65.8% (95%CI 50.3%-81.3%) vs 54.4% (95%CI 37.7%-71.1%), P=0.955] were comparable between the two groups. 2-year overall survival (OS) was significantly better in ATG group than the control one [83.8% (95% CI 71.8%-90.0%) vs 58.0% (95% CI 42.2%-73.9%), P=0.019].@*Conclusion@#The addition of low-dose ATG decreased the incidence of aGVHD and improved OS. The incidences of viral infections and disease relapse remained to be similar between the two groups. These results suggested that elderly patients undergoing MSD-PBSCT may benefit from this low-dose ATG containing GVHD prophylaxis regimen.

Does anti-thymocyte globulin have a place in busulfan/fludarabine conditioning for matched related donor hematopoietic stem cell transplantation?

BACKGROUND/AIMS: There is controversy about the prophylactic effect of anti-thymocyte globulin (ATG) on graft versus host disease (GVHD) in the setting of matched related-donor hematopoietic stem cell transplantation (HSCT). This study assessed the inf luences of ATG on the incidences of acute and chronic GVHD and other clinical outcomes in matched related-donor HSCT. METHODS: Sixty-one patients received allogeneic HSCT from human leukocyte antigen-matched, related donors. Patients received busulfan/fludarabine conditioning regimens and standard GVHD prophylaxis with or without additional ATG. RESULTS: There was no significant difference in the cumulative incidences of overall acute GVHD, grade II to IV acute GVHD at day 100, and chronic GVHD during the follow-up period between the ATG and non-ATG groups. Three-year overall survival rates were very similar, but three year disease-free survival of the non-ATG group was higher than that of the ATG group (56.2% for ATG vs. 63.1% for non-ATG, p = 0.597). Relapse rate at 3 years in the ATG group was slightly higher than that of the non-ATG group (37.5% vs. 20%, p = 0.29). Non-relapse mortality rate at 3 years was lower in the ATG group (6.25% vs. 15.6%, p = 0.668). CONCLUSIONS: Although the addition of ATG doesn't guarantee a reduction in the incidences of acute and chronic GVHD, pre-transplantation ATG may result in lower non-relapse mortality in the context of matched related-donor HSCT with a busulfan/fludarabine conditioning regimen. However, caution is needed when using ATG because of a possibility to increase relapse rate.

Evaluation of the efficacy of immunosuppressive therapy with rabbit-antithymocyte globulin combined with Cyclosporine in children with severe aplastic anemia / 中华实用儿科临床杂志

Objective To evaluate the efficacy and adverse reaction of the first line therapy with rabbit-antithymocyte globulin (ATG) combined with Cyclosporine (CsA) in children with acquired severe aplastic anemia.Methods A retrospective analysis was performed.The clinical data included 44 children with acquired severe aplastic anemia treated with ATG combined with CsA in Beijing Children's Hospital Affiliated to Capital Medical University between June 2006 and December 2013.The SPSS 19.0 statistical package was used for data analysis.Results Sixteen cases were severe aplastic anemia,and 28 cases were very severe aplastic anemia.The median age of treatment with ATG was 8 years old and 10 months.The median follow-up period was 24 months.The hematologic response rate was 66％ (29/44 cases) in 6 months after ATG treatment,and the overall response rate was 77％ (34/44 cases) at the endpoint of follow-up.The median time of partial remission (PR) was 3 months,of complete remission (CR) was 12 months.Eighty-five percent (29/34 cases)effective cases achieved PR during 6 months,while 56％ (15/27 cases)cases achieved CR in 12 months.There was no significant difference between the response rate with ATG treatment and gender,severity of disease,age,interval from clinical onset to ATG treatment,and ratio of CD4 +/CD8 +.The response rate in children without serum sickness was superior to that with serum disease(P =0.006).Thirty-four cases (77％) manifested immediate side-effects with ATG infusion.The side-effects included fever,chill,rash,gastrointestinal distress and irritable cough.The overall 2-year survival rate was 87.3％ (39/44 cases) and the 2-year transplantation-free survival rate was 82.5％ (37/44 cases) (x2 =0.34,P =0.56).Conclusions The response rate with rabbit-ATG combined with CsA in children with acquired severe aplastic anemia was 77％.The adverse reactions were minor.The immunosuppressive therapy should begin as soon as possible in children without chance for hematopoietic stem cell transplantation.

Comparison of the Clinical Outcomes between Anti-thymocyte Globulin and Basiliximab Induction Therapy in Deceased Donor Kidney Transplantation: Single Center Experience / 대한이식학회지

BACKGROUND: The aim of this study is to evaluate the clinical outcomes between anti-thymocyte globulin (ATG) and basiliximab induction in deceased donor kidney transplantation (DDKT). METHODS: Between May 2006 and February 2015, 40 patients underwent DDKT at our institution. Three cases (7.5%) of them were lost during the following-up schedule. In this study, ATG induction criteria were donor age >50 years old or donor creatinine level >1.3 mg/dL except hepatitis B virus positive and hepatitis C virus positive recipients. Recipients were divided into two groups: the ATG group (n=20) and the basiliximab group (n=17). RESULTS: The 1-year patient survival in the ATG group was 89.4% compared to 93.8% in the basiliximab group (P=0.989). Graft survival for a 1 year in the ATG and the basiliximab group was 89.1% and 93.8%, respectively (P=0.967). Incidences of acute rejection episodes were more prevalent in the basiliximab group (15.0% vs. 29.4%, P=0.428). The glomerular filtration rate level by period of recipients was not different in both group (12th month, 64.60+/-16.17 mg/dL vs. 68.51+/-18.60 mg/dL, P=0.544). The overall complications during the follow-up were not significantly different in both groups (90.0% vs. 76.5%, P=0.383). CONCLUSIONS: The results showed that there was no difference in the patient survival and graft survival between induction of ATG and basiliximab of the DDKT were not different. Therefore, use of both induction agents led to a good patient and graft survival and ATG might be a safe and preferable agent for relatively poor renal function of donor in kidney transplantation.

The cardiac adverse events associated with ATG-P in the treatment of severe aplastic anemia: case re¬port and literature review / 中国药学杂志

OBJECTIVE: To observe the cardiac adverse events associated with antithymocyte globulin (ATG) in the treatment of severe aplastic anemia (SAA), and analyze its possible pathogenetic mechanisms and prophylactic measures.

Effect of two biological immunologic induction therapies on renal transplant recipients / 器官移植

Objective Toevaluateefficacyandsafetyoftwodifferentbiologicalsinimmunologic inductiontherapyonrenaltransplantrecipients.Methods Clinicaldataof78renaltransplantrecipientswho received biological immunologic induction therapy in Department of Urology of the 452nd Hospital of Chinese People's Liberation Army from June 2008 to April 2013,were retrospectively analyzed. According to different biological immunologic induction therapy,the recipients were divided into two groups,monoclonal antibody group (group A,n=35,received treatment of basiliximab)and polyclonal antibody group [group B,n=43, received treatment of antithymocyte globulin (ATG)]. And the other recipients who didn't receive immunologic induction therapy in the hospital during the corresponding period were chosen as control group (group C,n=32). The survival rates of recipient and kidney in 3 groups at 12th weeks after transplantation were analyzed.The levels of serum creatinine (Scr)of recipients in 3 groups were monitored at 7,14,30,60 d after transplantation. The occurrence rates of complications including acute rejection,delayed graft function and infectionwerecomparedamong3groups.Results At12thweeksaftertransplantation,thesurvivalratesof recipient and kidney in 3 groups were 100% and 100% in group A,97.7% and 97.7% in group B,100%and 96.9% in group C. There was no significant difference among 3 groups (all in P>0.05 ). Compared with group C,the Scr levels in group A and B decreased significantly at 7,14 d after transplantation (all in P<0.05 ). Compared with group C,the incidence rates of acute rejection decreased in group A and B(all in P<0.05 ). There was no significant difference in the incidence rates of delayed graft function among 3 groups (all in P>0.05 ). The incidence rate of infection in group B was significantly higher than those in group A and C (allinP<0.05).Conclusions Immunologicinductiontherapyissafeandeffectiveintheapplicationon renal transplant recipients.

Comparison of the effectiveness and safety between lymphocytes scavenger and IL-2 receptor blocking agent induction in living kidney transplantation / 解放军医学杂志

Objective To compare the safety of two antibody inductors, namely lymphocytes scavenger and IL-2 receptor blocking agent, in living kidney transplantation. Methods The data of 191 patients, who received living kidney transplant in our hospital from Feb. 2007 to Jul. 2012, were retrospectively analyzed, and grouped according to the inductors they received as: a) lymphocytes scavenger group (n=56), with rabbit antithymocyte immunoglobulin (rATG, 4 cases) and porcine antihuman T-lymphocyte immunoglobulin (pATG, 52 cases) served as the inductor; b) IL-2 receptor blocking agent group (n=54), with basiliximab (40 cases) and daclizumab (14 cases) served as the inductor; and c) control group (n=8l). The incidence of rejection and infection, and the survival rate of patient/allograft within one year were then compared among the three groups. Results Within one year after the transplantation, the incidence of acute rejection in lymphocytes scavenger group, IL-2 receptor blocking agent group and control group was 12.5%, 11.1% and 28.4%, respectively. There was a significant difference between the two inductor groups and control group (P=0.003), but no significant difference was found between the two inductor groups (P>0.05). The incidence of delayed graft function (DGF) in the three groups was 8.9%, 7.4% and 13.6%, respectively, with no statistical significance (P>0.05). Also there was no significant difference among the three groups in the incidence of infection and the survival rate of patient/allograft within one year after transplantation (P>0.05). Conclusion Both inductors may significantly reduce the incidence of acute rejection within one year without increasing the incidence of infection and other adverse events, nor affect the postoperative patient/graft survival, so they are both safe and effective.

Pharmacokinetics of antithymocyte globulin in the treatment of childhood aplastic anemia / 中华实用儿科临床杂志

Objective To investigate the pharmacokinetics of antithymocyte globulin(ATG) in the treatment of childhood aplastic anemia(AA).Methods Six cases of of childhood AA treated with rabbit ATG (R-ATG,Genzyme company,USA and Fresenius company,Germany)were in the study.Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of ATG in plasma during the treatment period of the first day to the 5th day,and during the 7th,21th,35th,60th and 90th after the treatment finished respectively(all 12 time nodes).The pharmacokinetic data was detect with the Practical Pharmacokinetics-program(3P97).Results The peak levels of ATG concentrations in plasma(30-32 mg/L)were reached at the third to forth day during the treatment period,and then gradually descended to about half of the peak level in the 21st day(16-18 mg/L),and the microcomponent of ATG in plasma could be detected in the 90th day after the therapy.There were not evident difference of plasma concentrations in every time nodes,the peak levels,and pharmacokinetic data including the drug half-life,area under the plasma concentration-time curve (AUC) between the 2 forms of R-ATG (Genzyme company,USA and Fresenius company,Germany).The therapy effective rate in the 6 cases AA of this group was 66.7％ in the followed-up for mean 12 months.Conclusions Successfully set up the techniques to detect the pharmacokinetics of ATG in the treatment of childhood AA,will help to research the relationship between the pharmacokinetics with the side effects and outcomes of ATG in the treatment of AA.

Survival After Immunosuppressive Therapy in Children with Aplastic Anemia.

Objective: To determine the survival of children ≤18y, treated with immunosuppresive therapy (IST) using equine antithymocyte globulin (e-ATG) and cyclosporine (CsA). Design: Prospective data entry as per a specified format. Setting: Tertiary care hospital. Patients: From January 1998 to December 2009, 40 children were diagnosed with acquired aplastic anemia; 33 patients, who received IST, were analyzed. 31 children (94%) received one course of e-ATG and CsA. 2 patients (6%) received two courses of ATG. Intervention: Immunosuppressive therapy using equine ATG and cyclosporine. Main Outcome Measures: Overall response and overall survival. Results: The overall response (complete response + partial response) to IST at 6 months was 87.9%. 8 (24.2%) patients achieved CR, 21 (63.6%) patients had PR and 4 (12.1%) patients did not respond to IST. Median follow-up was 24 (6-102) months. Overall survival at 24 months was 90%, with an acturial survival of 85.4% at 5 years. Seventeen patients (51.5%) received G-CSF for a median duration of 32 (23-64) days. The patients who received G-CSF had fewer infectious complications (P=0.002), but G-CSF administration did not influence survival/ outcome. No patient developed myelodysplastic syndrome or acute leukemia. Conclusions: The survival of patients who respond to IST is excellent. Also, G-CSF reduces the infectious complications without conferring any survival advantage.