Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.
Male ; Female ; Humans ; Decitabine ; Myelodysplastic Syndromes/therapy* ; Leukemia, Myeloid, Acute/complications* ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Recurrence ; Chronic Disease ; Graft vs Host Disease/etiology* ; Transplantation Conditioning/adverse effects* ; Bronchiolitis Obliterans Syndrome ; Retrospective Studies

OBJECTIVE: To investigate the inhibitory effect of AZD2014, a dual mTORC1/2 inhibitor, against acute graft rejection in a rat model of allogeneic liver transplantation. METHODS: Liver transplantation from Lewis rat to recipient BN rat (a donor-recipient combination that was prone to induce acute graft rejection) was performed using Kamada's two-cuff technique. The recipient BN rats were randomized into 2 groups for treatment with daily intraperitoneal injection of AZD2014 (5 mg/kg, n=4) or vehicle (2.5 mL/kg, n=4) for 14 consecutive days, starting from the first day after the transplantation. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels of the rats were measured 3 days before and at 1, 3, 5, 7, 10, and 14 days after the transplantation, and the survival time of the rats within 14 days were recorded. Immunohistochemical staining was used to examine the expressions of CD3 and Foxp3 in the liver graft, and acute graft rejection was assessed using HE staining based on the Banff schema. RESULTS: Three rats in the control group died within 14 days after the surgery, while no death occurred in the AZD2014 group, demonstrating a significantly longer survival time of the rats in AZD2014 group (χ²=4.213, P=0.04). Serum ALT, AST and TBIL levels in the control group increased progressively after the surgery and were all significantly higher than those in AZD2014 group at the same time point (P < 0.05). Pathological examination revealed significantly worse liver graft rejection in the control group than in AZD2014 group based on assessment of the rejection index (P < 0.01); the rats in the control group showed more serious T lymphocyte infiltration and significantly fewer Treg cells in the liver graft than those in AZD2014 group (P < 0.01). CONCLUSIONS AZD2014 can effectively inhibit acute graft rejection in rats with allogeneic liver transplantation.
Animals ; Benzamides ; Graft Rejection/prevention & control* ; Graft Survival ; Liver/pathology* ; Liver Transplantation ; Mechanistic Target of Rapamycin Complex 1 ; Morpholines ; Pyrimidines ; Rats ; Rats, Inbred Lew

BACKGROUND: Although ABO-incompatible (ABOi) kidney transplantation (KT) has been performed successfully, a standard preconditioning regimen has not been established. Based on the initial antidonor ABO antibody titers, an individualized preconditioning regimen is developed, and this study explored the efficacy and safety of the regimen. METHODS: From September 1, 2014, to September 1, 2020, we performed 1668 consecutive living-donor KTs, including 100 ABOi and 1568 ABO-compatible (ABOc) KTs. ABOi KT recipients (KTRs) with a lower antibody titer (≤1:8) were administered oral immunosuppressive drugs (OIs) before KT, while patients with a medium titer (1:16) received OIs plus antibody-removal therapy (plasma exchange/double-filtration plasmapheresis), patients with a higher titer (≥1:32) were in addition received rituximab (Rit). Competing risk analyses were conducted to estimate the cumulative incidence of infection, acute rejection (AR), graft loss, and patient death. RESULTS: After propensity score analyses, 100 ABOi KTRs and 200 matched ABOc KTRs were selected. There were no significant differences in graft and patient survival between the ABOi and ABOc groups (P  = 0.787, P  = 0.386, respectively). After using the individualized preconditioning regimen, ABOi KTRs showed a similar cumulative incidence of AR (10.0% υs . 10.5%, P  = 0.346). Among the ABOi KTRs, the Rit-free group had a similar cumulative incidence of AR ( P  = 0.714) compared to that of the Rit-treated group. Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection (HR: 0.31; 95% CI: 0.12-0.78, P  = 0.013). Notably, antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen ( P  = 0.013) than those receiving Rit. ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR (HR: 2.72, 95% CI: 1.01-7.31, P  = 0.048). ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year. CONCLUSIONS An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT. Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers; however, antibody titer rebound should be monitored.
Humans ; Kidney Transplantation/adverse effects* ; Living Donors ; Kidney ; Immunosuppressive Agents/therapeutic use* ; Rituximab/therapeutic use* ; ABO Blood-Group System ; Graft Rejection ; Graft Survival

OBJECTIVE: To investigate the clinical efficacy and survival factors of microtransplantation (MST) in adult patients with acute myeloid leukemia (AML). METHODS: For a retrospective analysis of 27 adult patients with AML receiving MST from July 2014 to October 2021, the median age was 59(29-77) years old, 13 cases were ≥60 years old, 14 case were <60 years old, 13 cases were male and 14 cases were female. Classification by FAB: AML-M2 6 cases, AML-M4 6 cases, AML-M5 2 cases, AML-M6 2 cases, AML（Undivided type） 9 cases, AML myeloid sarcoma 2 cases (primary AML 21 cases, AML secondary to MDS 6 cases). Cytogenetic analysis showed 25 patients with a normal karyotype, 2 patients with an abnormal karyotype, and 20 patients with an abnormal molecular biology. Induction chemotherapy regimens mainly include: IA, DA, MA or HA regimen, including CAG or CIG in combination with decitabine, and single-agent decitabine. 17 patients achieved complete remission (CR) after 1 course of induction chemotherapy and 4 patients achieved CR after 2 courses of induction chemotherapy. 3 patients received CR by four courses of decitabine, 2 patients received no remission, and 1 patient underwent no induction chemotherapy and were treated direct MST. There were 16 patients with pretransplant CR and 11 patients were not in remission before transplantation. Follow-up mainly used consult patient's medical records and telephone inquiry to observe the adverse effects and efficacy of MST treatment. Survival analysis was performed by Kaplan-Meier method, with the main observation indicators overall survival(OS) and leukemia-free survival(LFS), and performed with the Log-rank test. Multivariate analysis was performed by the Cox regression model. RESULTS: A total of 79 MST were performed in 27 AML patients with good overall safety and no special serious adverse effects. The median time of leukocyte recovery was 13(4-28) days, and the median time of platelet recovery was 13(4-30) days. There were 50 cases of infection, 5 cases of abnormal liver function and 3 cases of abnormal cardiac function. Except for abnormal cardiac function, all other complications did not affect the treatment and were cure. Acute or chronic GVHD, renal insufficiency, abnormal coagulation function, and severe bleeding were not observed during treatment or during follow-up. As of the follow-up date, the median follow-up time of the 27 patients was 79(14-171) months, the median OS time was 62(1-171) months, and the median LFS time was 15(0-171) months. The 2-year OS rate was 65.7%（17/27）, and the 2-year LFS rate was 47.4%（12/27） . The complete response rate of 27 patients treated with MST was 48.1% (13/27). 8 patients relapsed during MST treatment, including 7 patients after the completion of the first MST course and 1 patient after the completion of the second MST course. 2 patients relapsed after the end of the course of MST. 13 patients died, including 10 patients because of disease progression, two patients from severe infection, and one patient from cardiac damage. CONCLUSION MST has the advantages of small toxic side effects, complete compatibility of HLA matching is not required, effective avoidance of GVHD and rapid hematopoietic recovery, which can improve OS and LFS in elderly AML and young AML patients, and is one of the treatment options for patients without HLA matching.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cytarabine ; Decitabine/therapeutic use* ; Female ; Graft vs Host Disease/drug therapy* ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Male ; Middle Aged ; Remission Induction ; Retrospective Studies ; Survival Analysis ; Treatment Outcome

Objectives: To evaluate the effects of steatotic donor livers on the safety of donors and the prognosis of donors and recipients in pediatric living donor liver transplantation. Methods: A total of 814 pediatric living donor liver transplantations were performed between January 2013 and December 2020 at Department of Pediatric Organ Transplantation,Tianjin First Central Hospital.The clinical data were collected and a retrospective study was conducted.The recipients and the donors were divided into non-steatotic donor liver group(n=733) and steatotic donor liver group(n=81) according to whether the donor graft had steatosis. The recipients and the donors in the steatotic donor liver group were further divided into mild and moderate steatosis groups based on the degree of liver steatosis.Among the donors of non-steatosis donor group,there were 307 males and 426 females,with a median age of 30 years(range:18 to 57 years);the recipients included 351 males and 382 females,with a median age of 7 months(range:4 month to 14 years).Among the donors of steatosis donor group,there were 41 males and 40 females,with a median age of 31 years(range:22 to 51 years);the recipients included 34 males and 47 females,with a median age of 8 months(range:5 months to 11 years).The donors and the recipients were followed up regularly by means of outpatient reexamination and questionnaire survey after operation.Statistical analysis of data between groups was performed using t-test,Wilcoxon rank-sum test,repeated measures ANOVA,χ² test,or Fisher's exact test,respectively.The survival curves of recipients and grafts in different groups were created by Kaplan-Meier method,and the survival rates of the steatotic donor liver group and the non-steatotic donor liver group were compared by Log-rank method. Results: There was no significant difference in the gender of donors in both groups (P=0.132).There were significant differences in the age and blood type distribution as well as body weight and body mass index(all P<0.05) between the two groups.No significant difference was seen in the recovery of liver function markers ALT and AST at 1,2,5 days and 1 month after operation (all P>0.05) between the two groups.The steatotic donor liver group showed longer operation time ((294±75) minutes vs. (264±81) minutes; t=3.149,P=0.002),increased incidence of postoperative biliary leakage (3.7%(3/81) vs. 0.5% (4/733); P=0.025) and delayed incision healing (7.4%(6/81) vs. 2.0%(15/733); P=0.013).There were no significant differences in gender,age,blood type distribution,height,weight and pediatric end-stage liver disease score of recipients between the two groups (all P>0.05).As compared to the non-steatotic donor liver group,the steatotic donor liver group showed similar levels of ALT, AST and total bilirubin within 2 weeks after operation(all P>0.05). The cumulative recipient survival rates in both groups were both 96.3%,the cumulative graft survival rates were 96.3% and 95.5%,respectively,without significant difference(both P>0.05). No statistical difference was observed in the incidence of major complications between the two groups (all P>0.05). There was no significant difference in the recovery of liver function markers of donors and recipients between mild and moderate steatosis groups(all P>0.05).The cumulative recipient survival rates were both 95.9% and the cumulative graft survival rates were both 100% in mild and moderate steatosis groups,without significant difference(P=0.592). Conclusions: The application of mild to moderate steatotic donor livers in pediatric living donor liver transplantation may prolong the operation time of donors,increase the incidence of complications such as biliary leakage and delayed incision healing. But there is no significant impact of mild to moderate steatotic donor livers on the overall postoperative recovery of donors and recipients,and the prognosis is ideal.
Adolescent ; Adult ; Bilirubin ; Child ; End Stage Liver Disease/surgery* ; Fatty Liver/surgery* ; Female ; Graft Survival ; Humans ; Infant ; Infant, Newborn ; Liver ; Liver Transplantation/methods* ; Living Donors ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Tissue Donors ; Young Adult

Objective: To evaluate the short-and mid-term efficacy of pediatric kidney transplantation and the risk factors for kidney graft and recipient. Methods: The baseline data and postoperative complications of pediatric donors and recipients of 284 kidney transplants were retrospectively analyzed in the Department of Kidney Transplantation in the First Affiliated Hospital of Zhengzhou University from August 2010 to May 2021 and all subjects were followed up until December 31, 2021. According to the survival status of donors and recipients, they were divided into the graft-loss group and the graft-survival group, and the recipient death group and survival group, respectively. Univariate comparison between groups was performed by Log-rank test, and Cox proportional risk model was used to explore the independent risk factors for the graft and recipient survival. Results: Among the 284 children recipients, 184 cases (64.8%) were male and 100 cases(35.2%) were female, and 19 cases (6.7%) were living relative donor renal transplantation, 19 cases (6.7%) were preemptive transplantation, and 8 cases were secondary transplantation. The age of 284 recipients at the time of transplantation was 13.0 (9.0, 15.0) years, among whom 29 cases aged 0-6 years, 96 cases aged 7-11 years old, and 159 cases aged 12-18 years. The 1, 3, and 5 year survival rates were 92.3%, 88.9% and 84.8% for the kidney grafts, and were 97.1%, 95.6% and 94.4% for the recipients, respectively. Multivariate analysis showed postoperative acute rejection (HR=3.14, 95%CI 1.38-7.15, P=0.006) and perioperative vascular complications (HR=4.73, 95%CI 2.03-11.06, P<0.001) were independent risk factors for the survival of kidney graft. Postoperative infection (HR=14.23, 95%CI 3.45-58.72, P<0.001) was an independent risk factor for the postoperative mortality of recipients. Conclusions: Pediatric kidney transplantation shows a good short-and mid-term prognosis. Postoperative acute rejection and perioperative vascular complications are the risk factors for the survival of kidney graft, and postoperative infection is the risk factor affecting the survival of recipient.
Child ; Female ; Graft Rejection ; Graft Survival ; Humans ; Kidney Transplantation/adverse effects* ; Living Donors ; Male ; Postoperative Complications ; Prognosis ; Retrospective Studies ; Risk Factors

BACKGROUND: Delayed graft function (DGF) is the main cause of renal function failure after kidney transplantation. This study aims at investigating the value of hypothermic machine perfusion (HMP) parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor (DD) kidney transplantation. METHODS: HMP parameters, perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1, 2019 to August 31, 2019 in the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis. RESULTS: In this study, the DGF incidence was 17.7% (20/113); The multivariate logistic regression results showed that terminal resistance (OR: 1.879, 95% CI 1.145-3.56) and glutathione S-transferase (GST)(OR = 1.62, 95% CI 1.23-2.46) were risk factors for DGF; The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time (HR = 0.823, 95% CI 0.735-0.981). The model combining terminal resistance and GST (AUC = 0.888, 95% CI: 0.842-0.933) significantly improved the DGF predictability compared with the use of terminal resistance (AUC = 0.756, 95% CI 0.693-0.818) or GST alone (AUC = 0.729, 95% CI 0.591-0.806). CONCLUSION According to the factors analyzed in this study, the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.
Biomarkers ; Delayed Graft Function ; Graft Survival ; Humans ; Kidney/physiology* ; Kidney Transplantation/adverse effects* ; Organ Preservation ; Perfusion ; Retrospective Studies ; Tissue Donors

Antibody-mediated rejection (AMR) is a rare and serious complication after lung transplantation, with no characteristic of pathological manifestation, no systematic standard treatment, and the poor efficacy and prognosis. We reported a case of early AMR after lung transplantation and the relevant literature has been reviewed. A male patient presented with symptoms of cold 99 days after transplantation and resolved after symptomatic treatment. He admitted to the hospital 14 days later because of a sudden dyspnea and fever. Anti-bacteria, anti-fungi, anti-virus, and anti-pneumocystis carinii treatment were ineffective, and a dose of 1 000 mg methylprednisolone did not work too. The patient's condition deteriorated rapidly and tracheal intubation was done to maintain breathing. Serum panel reactive antibody and donor specific antibody showed postive in humen leukocyte antigen (HLA) II antibody. Pathological examination after transbronchial transplantation lung biopsy showed acute rejection. Clinical AMR was diagnosed combined the donor-specific antibody with the pathological result. The patient was functionally recovered after combined treatment with thymoglobuline, rituximab, plasmapheresis, and immunoglobulin. No chronic lung allograft dysfunction was found after 3 years follow up. We should alert the occurrence of AMR in lung transplantation recipient who admitted to hospital with a sudden dyspnea and fever while showed no effect after common anti-infection and anti-rejection treatment. Transbronchial transplantation lung biopsy and the presence of serum donor-specific antibody are helpful to the diagnosis. The treatment should be preemptive and a comprehensive approach should be adopted.
Graft Rejection ; Graft Survival ; HLA Antigens ; Humans ; Isoantibodies ; Lung Transplantation/adverse effects* ; Male

OBJECTIVE: To investigate the optimal dose range of immunosuppressants in patients with autosomal dominant polycystic kidney disease (ADPKD) after renal transplantation. METHODS: A cohort of 68 patients with ADPKD who received their first renal transplantation between March, 2000 and January, 2018 in our institute were retrospectively analyzed, with 68 non-ADPKD renal transplant recipients matched for gender, age and date of transplant as the control group. We analyzed the differences in patient and renal survival rates, postoperative complications and concentrations of immunosuppressive agents between the two groups at different time points within 1 year after kidney transplantation. The concentrations of the immunosuppressants were also compared between the ADPKD patients with urinary tract infections (UTI) and those without UTI after the transplantation. RESULTS: The recipients with ADPKD and the control recipients showed no significantly difference in the overall 1-, 5-, and 10- year patient survival rates (96.6% 96.0%, 94.1% 93.9%, and 90.6% 93.9%, respectively; > 0.05), 1-, 5-, and 10-year graft survival rates (95.2% 96.0%, 90.8% 87.2%, and 79.0% 82.3%, respectively; > 0.05), or the incidences of other post- transplant complications including acute rejection, gastrointestinal symptoms, cardiovascular events, pneumonia, and neoplasms ( > 0.05). The plasma concentrations of both tacrolimus and mycophenolate mofetil (MPA) in ADPKD group were significantly lower than those in the control group at 9 months after operation ( < 0.05). The incidence of UTI was significantly higher in ADPKD patients than in the control group ( < 0.05). In patients with ADPKD, those with UTI after transplantation had a significantly higher MPA plasma concentration ( < 0.05). CONCLUSIONS In patients with ADPKD after renal transplant, a higher dose of MPA is associated with a increased risk of UTI, and their plasma concentrations of immunosuppressants for long-term maintenance of immunosuppression regimen can be lower than those in other kidney transplantation recipients.
Graft Survival ; Humans ; Immunosuppressive Agents ; Kidney Transplantation ; Polycystic Kidney, Autosomal Dominant ; Retrospective Studies

Death ; Fatty Liver ; Graft Survival ; Humans ; Liver ; Liver Transplantation ; Living Donors ; Obesity ; Tissue Donors