Renal allograft rejection and its detection are challenging problems for transplant clinicians.Transplant physicians rely on serum creatinine,estimated glomerular filtration rate,proteinuria,donor-specific antibodies,...Renal allograft rejection and its detection are challenging problems for transplant clinicians.Transplant physicians rely on serum creatinine,estimated glomerular filtration rate,proteinuria,donor-specific antibodies,and graft biopsy to detect rejection.The sensitivity and specificity in these blood and urine tests are low,and the invasiveness of graft biopsy has led transplant clinicians to seek alternative diagnostic tools.Cell-free DNA(cfDNA)is a fragment of DNA released from cell death due to necrosis and apoptosis.Donor-derived cfDNA(dd-cfDNA)has been proposed as a potential non-invasive biomarker for detecting rejection.However,one must interpret it cautiously in conditions such as ischemia-reperfusion injury,delayed graft function,BK virus nephropathy,post-kidney biopsy,and dual kidney transplantation,which may cause dd-cfDNA elevation.There is a lack of standardized cutoff values for diagnosing various types of rejections.Low specificity,higher cost,and lack of universal availability are the multiple obstacles to using this tool.There is a need to establish clinical guidelines for its future utility in early rejection detection,graft surveillance,and tailoring of immunosuppression.展开更多
In recent years, the use of new biomarkers in different phases of the diagnosis andtreatment of several diseases has allowed substantial improvement in clinicalpractice. The use of donor-derived cell-free DNA (dd-cfDN...In recent years, the use of new biomarkers in different phases of the diagnosis andtreatment of several diseases has allowed substantial improvement in clinicalpractice. The use of donor-derived cell-free DNA (dd-cfDNA) in organ transplantationhas led to significant progress in the treatment of post-transplantoutcomes, particularly after kidney transplantation. In addition, the use of ddcfDNAin organ transplantation has led to significant advancements in posttransplantoutcome monitoring. The aim of this study is to review many of therecent studies on the use of this biomarker and to evaluate its most relevantadvantages and limitations. dd-cfDNA is released from several types of cells ofthe transplanted organ, most often from endothelial cells and this happens in thecase of organ damage, most often rejection. Its presence in the bloodstream of therecipients is an important sign of graft damage;its principal advantage is in theavoidance of invasive tools such as renal biopsy. Additionally, several studiesreported that the finding of dd-cfDNA in the serum may precede histologicalabnormalities;its utility in the diagnosis of subclinical rejection is extremelyimportant. Among the principal limitations of this tool are the difficulty in distinguishingdifferent forms of graft damage. According to several studies this toolhas several limitations in diagnosing T-cell mediated rejection. In addition,particular care should be taken in distinguishing dd-cfDNA from recipientderivedcfDNA.展开更多
Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after ...Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.展开更多
BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining...BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining is negative,because of the similarities in histopathology.This study investigated whether donor-derived cell-free DNA(ddcfDNA)can be used to differentiate BKPyVAN.Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function,22 with type I TCMR,21 with proven BKPy VAN,and 5 with possible Py VAN.We found that urinary ddcfDNA levels were upregulated in recipients with graft injury,whereas plasma ddcfDNA levels were comparable for all groups.The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients(10.4 vs.6.1 ng/mL,P<0.001 and 68.4%vs.55.3%,P=0.013,respectively).Urinary ddcfDNA fractions(not concentrations)were higher in the BKPyVAN-pure subgroup than in the BKPyVAN-rejection-like subgroup(81.30%vs.56.64%,P=0.025).With a cut-off value of 7.81 ng/m L,urinary ddcf DNA concentrations distinguished proven BKPyVAN from type I TCMR(area under the curve(AUC)=0.848,95%confidence interval(95%CI):0.734 to 0.963).These findings suggest that urinary ddcf DNA is a non-invasive biomarker which can reliably differentiate BKPy VAN from type I TCMR.展开更多
Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell ac...Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.展开更多
Objective Donor-derived carbapenem-resistant Klebsiella pneumoniae(CRKP)infection has recently emerged as a critical early complication after renal transplantation.Although CRKP is usually sensitive to tigecycline,mon...Objective Donor-derived carbapenem-resistant Klebsiella pneumoniae(CRKP)infection has recently emerged as a critical early complication after renal transplantation.Although CRKP is usually sensitive to tigecycline,monotherapy with this drug is often less than effective.We investigated the efficacy of a combined regimen of tigecycline with high-dose,extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation.Methods From Jan.2016 to Dec.2017,a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute.Probable or possible donor-derived infection(DDI)was identified in 8 transplant recipients.Clinical data were retrospectively analyzed.Results Klebsiella pneumoniae carbapenemase-2(KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation,leading to surgical site(n=3),urinary tract(n=4),and/or bloodstream(n=2)infections in 8 recipients.The drug susceptibility tests showed that CRKP was sensitive to tigecycline,but resistant to meropenem.In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem,DDIs were successfully cured.The length of hospital stay was 31(18–129)days,and the serum creatinine at discharge was 105.8±16.7µmol/L.The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock.A median follow-up of 43 months(33–55)showed no recurrence of new CRKP infection in the 7 surviving recipients.Conclusion It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.展开更多
Donor-derived infection(DDI)associated with Scedosporium spp is extremely rare,and results in a very poor prognosis.The present study reports a probable DDI due to Scedosporium boydii(S.boydii)from a donor with neurop...Donor-derived infection(DDI)associated with Scedosporium spp is extremely rare,and results in a very poor prognosis.The present study reports a probable DDI due to Scedosporium boydii(S.boydii)from a donor with neuropsychiatric systemic lupus erythematosus.Two recipients developed Scedosporiosis after kidney transplantation from the same donor.Recipient 1 died of central nervous system infection due to S.boydii based on the clinical presentations,and the positive metagenomic next-generation sequencing(mNGS)and culture results for the cerebrospinal fluid.The other recipient with urinary tract obstruction due to S.boydii,which was identified through the positive culture and mNGS results of the removed stents,was successfully treated by stent replacement and voriconazole administration.Undiagnosed disseminated donor infection and the transmission of S.boydii should be given attention,particularly when the donor and recipients have primary immunodeficiency disease.The screening of donors and recipients for S.boydii using mNGS may be helpful in guiding antifungal prophylaxis and treatment recipients,due to its higher sensitivity and shorter diagnostic time relative to other traditional techniques.展开更多
Traditional monitoring of kidney transplant recipients for allograft dysfunction caused by rejection involves serial checks of serum creatinine with biopsy of the renal allograft if dysfunction is suspected.This appro...Traditional monitoring of kidney transplant recipients for allograft dysfunction caused by rejection involves serial checks of serum creatinine with biopsy of the renal allograft if dysfunction is suspected.This approach is labor-intensive,invasive and costly.In addition,because this approach relies on a rise in serum creatinine above historical baselines,injury to the allograft can be extensive before this rise occurs.In an effort to address this,donor-derived cell-free DNA(dd-cf DNA)is being used with increasing frequency in the clinical setting as a means of diagnosing a rejection of the renal allograft early in the course.This can poten-tially allow for early intervention to minimize not only injury,but the intensity of antirejection therapy needed and the avoidance of side effects.Here,we will review the available methodology for the determination and quantification of dd-cf DNA,the data supporting its use in clinical practice and the limitations of this technology.展开更多
Monitoring kidney transplants for rejection conventionally includes serum creatinine,immunosuppressive drug levels,proteinuria,and donor-specific antibody(DSA).Serum creatinine is a late marker of allograft injury,and...Monitoring kidney transplants for rejection conventionally includes serum creatinine,immunosuppressive drug levels,proteinuria,and donor-specific antibody(DSA).Serum creatinine is a late marker of allograft injury,and the predictive ability of DSA regarding risk of rejection is variable.Histological analysis of an allograft biopsy is the standard method for diagnosing rejection but is invasive,inconvenient,and carries risk of complications.There has been a long quest to find a perfect biomarker that noninvasively predicts tissue injury caused by rejection at an early stage,so that diagnosis and treatment could be pursued without delay in order to minimize irreversible damage to the allograft.In this review,we discuss relatively novel research on identifying biomarkers of tissue injury,specifically elaborating on donor-derived cell-free DNA,and its clinical utility.展开更多
Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leu...Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n=11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n=9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.展开更多
In January 2019,the fourth rabies case caused by organ transplantation was noticed in China,with the conditions of one per year for the recent four years.Different from the previous cases,there were no definite epidem...In January 2019,the fourth rabies case caused by organ transplantation was noticed in China,with the conditions of one per year for the recent four years.Different from the previous cases,there were no definite epidemiological histories of exposure or rabies-related symptoms from this patient.This case strongly supports the call for the legislation of establishing a national-level management that will incorporate the screening programs on donors prior to the practice of organ transplantation to reduce the risks on rabies caused by organ transplantation.展开更多
Compared with patients who undergo renal and islet transplantation sequentially,simultaneous omentum intraomental bio-scaf-fold islet-kidney transplantation in patients with type 1 diabetes complicated by renal failur...Compared with patients who undergo renal and islet transplantation sequentially,simultaneous omentum intraomental bio-scaf-fold islet-kidney transplantation in patients with type 1 diabetes complicated by renal failure has the advantages of donor homolo-gation,less trauma,lower cost,and easier acceptance by patients.Omentum intraomental bio-scaffold islet has been gradually applied in clinical practice,and rare clinical complications have been reported.Here we report a case of abdominal abscess associated with extended-spectrum β-lactamase in a patient who underwent simultaneous omentum intraomental bio-scaffold islet-kidney transplantation;the islet grafts remained partially functional after appropriate anti-infective treatment.展开更多
文摘Renal allograft rejection and its detection are challenging problems for transplant clinicians.Transplant physicians rely on serum creatinine,estimated glomerular filtration rate,proteinuria,donor-specific antibodies,and graft biopsy to detect rejection.The sensitivity and specificity in these blood and urine tests are low,and the invasiveness of graft biopsy has led transplant clinicians to seek alternative diagnostic tools.Cell-free DNA(cfDNA)is a fragment of DNA released from cell death due to necrosis and apoptosis.Donor-derived cfDNA(dd-cfDNA)has been proposed as a potential non-invasive biomarker for detecting rejection.However,one must interpret it cautiously in conditions such as ischemia-reperfusion injury,delayed graft function,BK virus nephropathy,post-kidney biopsy,and dual kidney transplantation,which may cause dd-cfDNA elevation.There is a lack of standardized cutoff values for diagnosing various types of rejections.Low specificity,higher cost,and lack of universal availability are the multiple obstacles to using this tool.There is a need to establish clinical guidelines for its future utility in early rejection detection,graft surveillance,and tailoring of immunosuppression.
文摘In recent years, the use of new biomarkers in different phases of the diagnosis andtreatment of several diseases has allowed substantial improvement in clinicalpractice. The use of donor-derived cell-free DNA (dd-cfDNA) in organ transplantationhas led to significant progress in the treatment of post-transplantoutcomes, particularly after kidney transplantation. In addition, the use of ddcfDNAin organ transplantation has led to significant advancements in posttransplantoutcome monitoring. The aim of this study is to review many of therecent studies on the use of this biomarker and to evaluate its most relevantadvantages and limitations. dd-cfDNA is released from several types of cells ofthe transplanted organ, most often from endothelial cells and this happens in thecase of organ damage, most often rejection. Its presence in the bloodstream of therecipients is an important sign of graft damage;its principal advantage is in theavoidance of invasive tools such as renal biopsy. Additionally, several studiesreported that the finding of dd-cfDNA in the serum may precede histologicalabnormalities;its utility in the diagnosis of subclinical rejection is extremelyimportant. Among the principal limitations of this tool are the difficulty in distinguishingdifferent forms of graft damage. According to several studies this toolhas several limitations in diagnosing T-cell mediated rejection. In addition,particular care should be taken in distinguishing dd-cfDNA from recipientderivedcfDNA.
文摘Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.
基金the Science and Technology Department of Zhejiang Province(No.2019C03029)the Bethune Charitable Foundation(No.G-X-2019-0101-12)+1 种基金the National Natural Science Foundation of China(Nos.81870510,81770719,81770752,and 81370851)the Zhejiang Provincial Natural Science Foundation of China(No.LQ18H050002)。
文摘BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining is negative,because of the similarities in histopathology.This study investigated whether donor-derived cell-free DNA(ddcfDNA)can be used to differentiate BKPyVAN.Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function,22 with type I TCMR,21 with proven BKPy VAN,and 5 with possible Py VAN.We found that urinary ddcfDNA levels were upregulated in recipients with graft injury,whereas plasma ddcfDNA levels were comparable for all groups.The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients(10.4 vs.6.1 ng/mL,P<0.001 and 68.4%vs.55.3%,P=0.013,respectively).Urinary ddcfDNA fractions(not concentrations)were higher in the BKPyVAN-pure subgroup than in the BKPyVAN-rejection-like subgroup(81.30%vs.56.64%,P=0.025).With a cut-off value of 7.81 ng/m L,urinary ddcf DNA concentrations distinguished proven BKPyVAN from type I TCMR(area under the curve(AUC)=0.848,95%confidence interval(95%CI):0.734 to 0.963).These findings suggest that urinary ddcf DNA is a non-invasive biomarker which can reliably differentiate BKPy VAN from type I TCMR.
基金supported by grants from the National Natural Science Foundation of China(No.82020108004)the Hospital-level Clinical Innovation Military-Civilian Special Project of Army Medical University(No.2018JSLC0020)+1 种基金Chongqing Science and Technology Innovation Leading Talent(No.CSTCCXLJRC201718)Natural Science Foundation of Chongqing Innovation Group Science Program(No.cstc2021jcyj-cxttX0001).
文摘Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.
基金supported by grants from Non-Profit Central Research Institute Fund of Chinese Academy of Medical Science(No.2018PT32018)Hubei Science and Technology Plan(No.2017ACA096).
文摘Objective Donor-derived carbapenem-resistant Klebsiella pneumoniae(CRKP)infection has recently emerged as a critical early complication after renal transplantation.Although CRKP is usually sensitive to tigecycline,monotherapy with this drug is often less than effective.We investigated the efficacy of a combined regimen of tigecycline with high-dose,extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation.Methods From Jan.2016 to Dec.2017,a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute.Probable or possible donor-derived infection(DDI)was identified in 8 transplant recipients.Clinical data were retrospectively analyzed.Results Klebsiella pneumoniae carbapenemase-2(KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation,leading to surgical site(n=3),urinary tract(n=4),and/or bloodstream(n=2)infections in 8 recipients.The drug susceptibility tests showed that CRKP was sensitive to tigecycline,but resistant to meropenem.In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem,DDIs were successfully cured.The length of hospital stay was 31(18–129)days,and the serum creatinine at discharge was 105.8±16.7µmol/L.The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock.A median follow-up of 43 months(33–55)showed no recurrence of new CRKP infection in the 7 surviving recipients.Conclusion It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.
基金supported by National Key Clinical Specialty Construction Project(General Surgery).
文摘Donor-derived infection(DDI)associated with Scedosporium spp is extremely rare,and results in a very poor prognosis.The present study reports a probable DDI due to Scedosporium boydii(S.boydii)from a donor with neuropsychiatric systemic lupus erythematosus.Two recipients developed Scedosporiosis after kidney transplantation from the same donor.Recipient 1 died of central nervous system infection due to S.boydii based on the clinical presentations,and the positive metagenomic next-generation sequencing(mNGS)and culture results for the cerebrospinal fluid.The other recipient with urinary tract obstruction due to S.boydii,which was identified through the positive culture and mNGS results of the removed stents,was successfully treated by stent replacement and voriconazole administration.Undiagnosed disseminated donor infection and the transmission of S.boydii should be given attention,particularly when the donor and recipients have primary immunodeficiency disease.The screening of donors and recipients for S.boydii using mNGS may be helpful in guiding antifungal prophylaxis and treatment recipients,due to its higher sensitivity and shorter diagnostic time relative to other traditional techniques.
文摘Traditional monitoring of kidney transplant recipients for allograft dysfunction caused by rejection involves serial checks of serum creatinine with biopsy of the renal allograft if dysfunction is suspected.This approach is labor-intensive,invasive and costly.In addition,because this approach relies on a rise in serum creatinine above historical baselines,injury to the allograft can be extensive before this rise occurs.In an effort to address this,donor-derived cell-free DNA(dd-cf DNA)is being used with increasing frequency in the clinical setting as a means of diagnosing a rejection of the renal allograft early in the course.This can poten-tially allow for early intervention to minimize not only injury,but the intensity of antirejection therapy needed and the avoidance of side effects.Here,we will review the available methodology for the determination and quantification of dd-cf DNA,the data supporting its use in clinical practice and the limitations of this technology.
文摘Monitoring kidney transplants for rejection conventionally includes serum creatinine,immunosuppressive drug levels,proteinuria,and donor-specific antibody(DSA).Serum creatinine is a late marker of allograft injury,and the predictive ability of DSA regarding risk of rejection is variable.Histological analysis of an allograft biopsy is the standard method for diagnosing rejection but is invasive,inconvenient,and carries risk of complications.There has been a long quest to find a perfect biomarker that noninvasively predicts tissue injury caused by rejection at an early stage,so that diagnosis and treatment could be pursued without delay in order to minimize irreversible damage to the allograft.In this review,we discuss relatively novel research on identifying biomarkers of tissue injury,specifically elaborating on donor-derived cell-free DNA,and its clinical utility.
文摘Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n=11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n=9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.
基金supported by the Key Technologies R&D Programof the National Ministry of Science(2017YFC1200503).
文摘In January 2019,the fourth rabies case caused by organ transplantation was noticed in China,with the conditions of one per year for the recent four years.Different from the previous cases,there were no definite epidemiological histories of exposure or rabies-related symptoms from this patient.This case strongly supports the call for the legislation of establishing a national-level management that will incorporate the screening programs on donors prior to the practice of organ transplantation to reduce the risks on rabies caused by organ transplantation.
基金partially supported by the National Key Research and Development Program of China(2020YFA0803704)National Natural Science Found of China(82070805).
文摘Compared with patients who undergo renal and islet transplantation sequentially,simultaneous omentum intraomental bio-scaf-fold islet-kidney transplantation in patients with type 1 diabetes complicated by renal failure has the advantages of donor homolo-gation,less trauma,lower cost,and easier acceptance by patients.Omentum intraomental bio-scaffold islet has been gradually applied in clinical practice,and rare clinical complications have been reported.Here we report a case of abdominal abscess associated with extended-spectrum β-lactamase in a patient who underwent simultaneous omentum intraomental bio-scaffold islet-kidney transplantation;the islet grafts remained partially functional after appropriate anti-infective treatment.
