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Bone Marrow Transplantation Apr 2023Post-transplant lymphoproliferative disorder (PTLD) is a leading cause of cancer death in solid organ transplant recipients (SOTRs). Relapsed or refractory (R/R) PTLD... (Review)
Review
Post-transplant lymphoproliferative disorder (PTLD) is a leading cause of cancer death in solid organ transplant recipients (SOTRs). Relapsed or refractory (R/R) PTLD portends a high risk of death and effective management is not well established. CD19-targeted CAR-T cell therapy has been utilized, but the risks and benefits are unknown. We report the first case of diffuse large B-cell lymphoma (DLBCL) PTLD treated with lisocabtagene maraleucel and present a systematic literature review of SOTRs with PTLD treated with CD19 CAR-T therapy. Our patient achieved a complete response (CR) with limited toxicity but experienced a CD19 relapse 8 months after infusion despite CAR-T persistence. Literature review revealed 14 DLBCL and 2 Burkitt lymphoma PTLD cases treated with CD19 CAR-T cells. Kidney (n = 12), liver (n = 2), heart (n = 2), and pancreas after kidney (n = 1) transplant recipients were analyzed. The objective response rate (ORR) was 82.4% (14/17), with 58.5% (10/17) CRs and a 6.5-month median duration of response. Among kidney transplant recipients, the ORR was 91.7% (11/12). Allograft rejection occurred in 23.5% (4/17). No graft failure occurred. Our analysis suggests that CD19 CAR-T therapy offers short-term effectiveness and manageable toxicity in SOTRs with R/R PTLD. Further investigation through larger datasets and prospective study is needed.
Topics: Humans; Antigens, CD19; Epstein-Barr Virus Infections; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Lymphoproliferative Disorders; Neoplasm Recurrence, Local; Organ Transplantation; Receptors, Chimeric Antigen; Transplant Recipients
PubMed: 36575360
DOI: 10.1038/s41409-022-01907-z -
The Cochrane Database of Systematic... Sep 2022Non-adherence to immunosuppressant therapy is a significant concern following a solid organ transplant, given its association with graft failure. Adherence to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-adherence to immunosuppressant therapy is a significant concern following a solid organ transplant, given its association with graft failure. Adherence to immunosuppressant therapy is a modifiable patient behaviour, and different approaches to increasing adherence have emerged, including multi-component interventions. There has been limited exploration of the effectiveness of interventions to increase adherence to immunosuppressant therapy.
OBJECTIVES
This review aimed to look at the benefits and harms of using interventions for increasing adherence to immunosuppressant therapies in solid organ transplant recipients, including adults and children with a heart, lung, kidney, liver and pancreas transplant.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 14 October 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
All randomised controlled trials (RCTs), quasi-RCTs, and cluster RCTs examining interventions to increase immunosuppressant adherence following a solid organ transplant (heart, lung, kidney, liver, pancreas) were included. There were no restrictions on language or publication type.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles and abstracts of identified records, evaluated study quality and assessed the quality of the evidence using the GRADE approach. The risk of bias was assessed using the Cochrane tool. The ABC taxonomy for measuring medication adherence provided the analysis framework, and the primary outcomes were immunosuppressant medication initiation, implementation (taking adherence, dosing adherence, timing adherence, drug holidays) and persistence. Secondary outcomes were surrogate markers of adherence, including self-reported adherence, trough concentration levels of immunosuppressant medication, acute graft rejection, graft loss, death, hospital readmission and health-related quality of life (HRQoL). Meta-analysis was conducted where possible, and narrative synthesis was carried out for the remainder of the results.
MAIN RESULTS
Forty studies involving 3896 randomised participants (3718 adults and 178 adolescents) were included. Studies were heterogeneous in terms of the type of intervention and outcomes assessed. The majority of studies (80%) were conducted in kidney transplant recipients. Two studies examined paediatric solid organ transplant recipients. The risk of bias was generally high or unclear, leading to lower certainty in the results. Initiation of immunosuppression was not measured by the included studies. There is uncertain evidence of an association between immunosuppressant medication adherence interventions and the proportion of participants classified as adherent to taking immunosuppressant medication (4 studies, 445 participants: RR 1.09, 95% CI 0.95 to 1.20; I² = 78%). There was very marked heterogeneity in treatment effects between the four studies evaluating taking adherence, which may have been due to the different types of interventions used. There was evidence of increasing dosing adherence in the intervention group (8 studies, 713 participants: RR 1.14, 95% CI 1.03 to 1.26, I² = 61%). There was very marked heterogeneity in treatment effects between the eight studies evaluating dosing adherence, which may have been due to the different types of interventions used. It was uncertain if an intervention to increase immunosuppressant adherence had an effect on timing adherence or drug holidays. There was limited evidence that an intervention to increase immunosuppressant adherence had an effect on persistence. There was limited evidence that an intervention to increase immunosuppressant adherence had an effect on secondary outcomes. For self-reported adherence, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the proportion of participants classified as medically adherent to immunosuppressant therapy (9 studies, 755 participants: RR 1.21, 95% CI 0.99 to 1.49; I² = 74%; very low certainty evidence). Similarly, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the mean adherence score on self-reported adherence measures (5 studies, 471 participants: SMD 0.65, 95% CI -0.31 to 1.60; I² = 96%; very low certainty evidence). For immunosuppressant trough concentration levels, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the proportion of participants who reach target immunosuppressant trough concentration levels (4 studies, 348 participants: RR 0.98, 95% CI 0.68 to 1.40; I² = 40%; very low certainty evidence). It is uncertain whether an intervention to increase adherence to immunosuppressant medication may reduce hospitalisations (5 studies, 460 participants: RR 0.67, 95% CI 0.44 to 1.02; I² = 64%; low certainty evidence). There were limited, low certainty effects on patient-reported health outcomes such as HRQoL. There was no clear evidence to determine the effect of interventions on secondary outcomes, including acute graft rejection, graft loss and death. No harms from intervention participation were reported.
AUTHORS' CONCLUSIONS
Interventions to increase taking and dosing adherence to immunosuppressant therapy may be effective; however, our findings suggest that current evidence in support of interventions to increase adherence to immunosuppressant therapy is overall of low methodological quality, attributable to small sample sizes, and heterogeneity identified for the types of interventions. Twenty-four studies are currently ongoing or awaiting assessment (3248 proposed participants); therefore, it is possible that findings may change with the inclusion of these large ongoing studies in future updates.
Topics: Adolescent; Adult; Child; Graft Rejection; Humans; Immunosuppressive Agents; Medication Adherence; Organ Transplantation; Transplant Recipients
PubMed: 36094829
DOI: 10.1002/14651858.CD012854.pub2 -
Transplant International : Official... 2022This guideline, from a European Society of Organ Transplantation (ESOT) working group, concerns the management of kidney transplant patients with HLA antibodies....
This guideline, from a European Society of Organ Transplantation (ESOT) working group, concerns the management of kidney transplant patients with HLA antibodies. Sensitization should be defined using a virtual parameter such as calculated Reaction Frequency (cRF), which assesses HLA antibodies derived from the actual organ donor population. Highly sensitized patients should be prioritized in kidney allocation schemes and linking allocation schemes may increase opportunities. The use of the ENGAGE 5 ((Bestard et al., Transpl Int, 2021, 34: 1005-1018) system and online calculators for assessing risk is recommended. The Eurotransplant Acceptable Mismatch program should be extended. If strategies for finding a compatible kidney are very unlikely to yield a transplant, desensitization may be considered and should be performed with plasma exchange or immunoadsorption, supplemented with IViG and/or anti-CD20 antibody. Newer therapies, such as imlifidase, may offer alternatives. Few studies compare HLA incompatible transplantation with remaining on the waiting list, and comparisons of morbidity or quality of life do not exist. Kidney paired exchange programs (KEP) should be more widely used and should include unspecified and deceased donors, as well as compatible living donor pairs. The use of a KEP is preferred to desensitization, but highly sensitized patients should not be left on a KEP list indefinitely if the option of a direct incompatible transplant exists.
Topics: Antibodies; HLA Antigens; Histocompatibility Testing; Humans; Kidney Transplantation; Living Donors; Quality of Life; Waiting Lists
PubMed: 36033645
DOI: 10.3389/ti.2022.10511 -
Transplantation Reviews (Orlando, Fla.) Dec 2022The number of transplants in the world is growing, although there is a demand that exceeds supply. It is worth mentioning that the costs for obtaining organs are... (Review)
Review
INTRODUCTION
The number of transplants in the world is growing, although there is a demand that exceeds supply. It is worth mentioning that the costs for obtaining organs are considered high. However, few studies have been developed on analyzing the costs of obtaining organs and tissues for transplants in order to support the decision-making of managers and health professionals.
OBJECTIVE
To summarize the studies related to the cost of obtaining organs for transplants from a deceased donor.
METHOD
A systematic literature review was conducted in the following databases: PubMed, Cochrane Library CINAHAL, Virtual Health Library (BVS), SCOPUS, Web of Science and EMBASE, using the following descriptors: Costs and cost analysis; Donor Selection; Tissue and Organ Procurement; Tissue and Organ Harvesting; and Tissue Donors, in studies published until April 2021. The risk of bias assessment was performed using the Joanna Briggs Institute's Checklist for Economic Assessments. It was not possible to perform a meta-analysis due to the heterogeneity of the studies.
RESULTS
A total of 1731 studies were identified, of which 11 were analyzed. The cost of kidneys in US dollars (USD) ranged between USD $1672 and USD $25,058. Obtaining a liver ranged from USD $586 to USD $44,478. Heart procurement ranged from USD $633 to USD $24,264. The combined heart-lung transplant ranged from USD $860 to USD $23,203. Obtaining the pancreas ranged from USD $413 to USD $29,708.
CONCLUSIONS
Cost of obtaining organs for transplants from a deceased donor is substantial and varies widely across different studies. The overall cost of failures to obtain organs is currently unknown. Understanding organ procurement expenses can help clarify areas in which organ and tissue procurement can improve in cost and efficiency.
Topics: Humans; Transplants; Tissue Donors; Tissue and Organ Procurement; Donor Selection; Kidney
PubMed: 36029555
DOI: 10.1016/j.trre.2022.100724 -
Surgery Nov 2022This systematic review and meta-analysis aimed to give an overview on the postoperative outcome after a minimally invasive (ie, laparoscopic and robot-assisted) central... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis aimed to give an overview on the postoperative outcome after a minimally invasive (ie, laparoscopic and robot-assisted) central pancreatectomy and open central pancreatectomy with a specific emphasis on the postoperative pancreatic fistula. For benign and low-grade malignant lesions in the pancreatic neck and body, central pancreatectomy may be an alternative to distal pancreatectomy. Exocrine and endocrine insufficiency occur less often after central pancreatectomy, but the rate of postoperative pancreatic fistula is higher.
METHODS
An electronic search was performed for studies on elective minimally invasive central pancreatectomy and open central pancreatectomy, which reported on major morbidity and postoperative pancreatic fistula in PubMed, Cochrane Register, Embase, and Google Scholar until June 1, 2021. A review protocol was developed a priori and registered in PROSPERO as CRD42021259738. A meta-regression was performed by using a random effects model.
RESULTS
Overall, 41 studies were included involving 1,004 patients, consisting of 158 laparoscopic minimally invasive central pancreatectomies, 80 robot-assisted minimally invasive central pancreatectomies, and 766 open central pancreatectomies. The overall rate of postoperative pancreatic fistula was 14%, major morbidity 14%, and 30-day mortality 1%. The rates of postoperative pancreatic fistula (17% vs 24%, P = .194), major morbidity (17% vs 14%, P = .672), and new-onset diabetes (3% vs 6%, P = .353) did not differ significantly between minimally invasive central pancreatectomy and open central pancreatectomy, respectively. Minimally invasive central pancreatectomy was associated with significantly fewer blood transfusions, less exocrine pancreatic insufficiency, and fewer readmissions compared with open central pancreatectomy. A meta-regression was performed with a random effects model between minimally invasive central pancreatectomy and open central pancreatectomy and showed no significant difference for postoperative pancreatic fistula (random effects model 0.16 [0.10; 0.24] with P = .789), major morbidity (random effects model 0.20 [0.15; 0.25] with P = .410), and new-onset diabetes mellitus (random effects model 0.04 [0.02; 0.07] with P = .651).
CONCLUSION
In selected patients and in experienced hands, minimally invasive central pancreatectomy is a safe alternative to open central pancreatectomy for benign and low-grade malignant lesions of the neck and body. Ideally, further research should confirm this with the main focus on postoperative pancreatic fistula and endocrine and exocrine insufficiency.
Topics: Humans; Laparoscopy; Pancreas; Pancreatectomy; Pancreatic Fistula; Pancreatic Neoplasms; Postoperative Complications; Retrospective Studies; Treatment Outcome
PubMed: 35987787
DOI: 10.1016/j.surg.2022.06.024 -
Transplantation Proceedings Sep 2022The ever-expanding organ supply and demand gap necessitates alternate sources of organ donors. Initially thought to be a contraindication, organ procurement from...
AIM
The ever-expanding organ supply and demand gap necessitates alternate sources of organ donors. Initially thought to be a contraindication, organ procurement from nonsurvivable burns patients is possibly an additional organ donor source. We aimed to conduct a systematic review investigating the prevalence and outcomes of the use of burn victims as a source of organ donation for transplantation.
METHODS
Medline and EMBASE were searched between 1990 and 2020, using the following keywords: organ procurement, organ donation, organ transplantation, and burns. Studies were not excluded based on patient numbers and included both published abstracts/conference proceeding and journal articles. Studies were excluded if specific organs were not identified or if posttransplant outcomes were not recorded. Primary and secondary outcomes of interest were post-transplantation organ function and complications respectively.
RESULTS
Six manuscripts met study inclusion criteria. Fourteen burns donors were identified, including both donation after circulatory death and donation after brain death pathways. The total body surface area of burn ranged from 4% to 90%. A total of 4 hearts, 2 lungs, 8 livers, 1 pancreas, and 24 kidneys were transplanted with varying duration of follow-up and outcomes.
CONCLUSION
A very small number of studies have reported the posttransplant outcomes of organs derived from victims of burn injury, including very limited information regarding graft function in the short or long term. Hence, recommendations for the utilization of organs from victims of burn injury should remain guarded and subject to surveillance.
Topics: Humans; Tissue Donors; Tissue and Organ Procurement; Organ Transplantation; Brain Death; Burns
PubMed: 35985876
DOI: 10.1016/j.transproceed.2022.05.027 -
Transplant Infectious Disease : An... Dec 2022West Nile virus (WNv) is a major cause of viral encephalitis in the United States. WNv infection is usually asymptomatic or a limited febrile illness in the...
UNLABELLED
West Nile virus (WNv) is a major cause of viral encephalitis in the United States. WNv infection is usually asymptomatic or a limited febrile illness in the immunocompetent hosts, although a small percentage can develop neuroinvasive disease. Neuroinvasive disease due to WNv in solid organ transplant recipients occurs at higher rates than observed in the general population and can have long term neurological sequalae.
METHODS
We retrospectively reviewed medical records of all solid organ transplant recipients at our institution who tested positive for WNv from 2010 to 2018. Two reviewers performed electronic searches of Medline, Embase, Cochrane Library of literature of WNv infections in SOT. Descriptive statistics were performed on key variables.
RESULTS
Eight recipients (mean age 54, five males) were diagnosed with neuroinvasive WNv infection at our institution. Distribution of infection was as follows: five kidney transplants, one in each kidney-pancreas, liver, and lung. Diagnoses included meningitis (3), encephalitis (1), meningo-encephalitis (4). Median time from transplant to infection was 49.8 months (2.7-175.4). No infections were considered donor-derived. Five patients received treatment with IVIG. Six patients were alive at median follow-up of 49.5 months (21.7-116.8). We identified 29 studies published from 2002 to 2019. Median time from transplant to infection was 14.2 months, with similar allograft distribution; 53% were donor-derived infections.
CONCLUSION
WNv infections in solid organ transplant recipients can be a consequence of organ donation or can be acquired via the community. Infections can be more severe in SOT recipients and lead to neuroinvasive disease.
Topics: Humans; Male; Middle Aged; Kidney Transplantation; Organ Transplantation; Retrospective Studies; United States; West Nile Fever; West Nile virus
PubMed: 35980220
DOI: 10.1111/tid.13929 -
Transplant Infectious Disease : An... Dec 2022We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk factors involved for an impaired response.
METHODS
We did a systematic review and meta-analysis of studies published up until January 11, 2022, that reported immunogenicity of COVID-19 vaccine among SOT. The study is registered with PROSPERO, number CRD42022300547.
RESULTS
Of the 1527 studies, 112 studies, which involved 15391 SOT and 2844 healthy controls, were included. SOT showed a low humoral response (effect size [ES]: 0.44 [0.40-0.48]) in overall and in control studies (log-Odds-ratio [OR]: -4.46 [-8.10 to -2.35]). The humoral response was highest in liver (ES: 0.67 [0.61-0.74]) followed by heart (ES: 0.45 [0.32-0.59]), kidney (ES: 0.40 [0.36-0.45]), kidney-pancreas (ES: 0.33 [0.13-0.53]), and lung (0.27 [0.17-0.37]). The meta-analysis for standard and booster dose (ES: 0.43 [0.39-0.47] vs. 0.51 [0.43-0.54]) showed a marginal increase of 18% efficacy. SOT with prior infection had higher response (ES: 0.94 [0.92-0.96] vs. ES: 0.40 [0.39-0.41]; p-value < .01). The seroresponse with mRNA-12723 mRNA was highest 0.52 (0.40-0.64). Mycophenolic acid (OR: 1.42 [1.21-1.63]) and Belatacept (OR: 1.89 [1.3-2.49]) had highest risk for nonresponse. SOT had a parallelly decreased cellular response (ES: 0.42 [0.32-0.52]) in overall and control studies (OR: -3.12 [-0.4.12 to -2.13]).
INTERPRETATION
Overall, SOT develops a suboptimal response compared to the general population. Immunosuppression including mycophenolic acid, belatacept, and tacrolimus is associated with decreased response. Booster doses increase the immune response, but further upgradation in vaccination strategy for SOT is required.
Topics: Humans; Abatacept; COVID-19; COVID-19 Vaccines; Mycophenolic Acid; Organ Transplantation; Transplant Recipients
PubMed: 35924679
DOI: 10.1111/tid.13926 -
Gastrointestinal Endoscopy Dec 2022Therapy and prognosis of pancreatic neuroendocrine tumors (PanNETs) are strictly related to the Ki-67 index, which defines tumor grading. The criterion standard for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Therapy and prognosis of pancreatic neuroendocrine tumors (PanNETs) are strictly related to the Ki-67 index, which defines tumor grading. The criterion standard for the assessment of grading of PanNETs is EUS-guided FNA (EUS-FBAFNA) or EUS-guided fine-needle biopsy sampling (EUS-FNB). Because data on diagnostic accuracy of EUS-FNA and EUS-FNB are heterogeneous, we aimed to analyze the variability in concordance between EUS grading and surgical grading.
METHODS
The MEDLINE, SCOPUS, and EMBASE databases were searched until November 2021 to identify studies reporting the concordance rate between EUS grading and surgical grading. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled events were calculated using a random-effects model and expressed in terms of pooled prevalence rates. A multivariate meta-regression was performed to find possible sources of heterogeneity. Where available, individual data were analyzed.
RESULTS
Twenty-six studies with 864 patients undergone EUS-FNA or EUS-FNB and surgical resection for PanNETs were included. The pooled estimate rate for the overall concordance of EUS grading and surgical grading was 80.3% (95% confidence interval, 75.6-85.1). Undergrading (EUS grading < surgical grading) was significantly more frequent with respect to overgrading (14.7% vs 3.5%, P < .001). Individual data analysis showed that among nonconcordant patients, the median Ki-67 difference was 3% (interquartile range, 2-6.15). The type of World Health Organization classification adopted and the median lesion diameter were significantly associated with heterogeneity at meta-regression.
CONCLUSIONS
EUS is an accurate technique in defining grading in patients with PanNETs, but a margin of error still exists, which should be the focus of future studies to minimize the risk of over- and/or undertreatment.
Topics: Humans; Neuroendocrine Tumors; Ki-67 Antigen; Pancreatic Neoplasms; Reproducibility of Results; Endoscopic Ultrasound-Guided Fine Needle Aspiration
PubMed: 35863518
DOI: 10.1016/j.gie.2022.07.014 -
Anticancer Research Jul 2022Minimally invasive pancreaticoduodenectomy (PD) is gaining popularity. The aim of this study was to compare the incidence of postoperative pancreatic fistula (POPF)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIM
Minimally invasive pancreaticoduodenectomy (PD) is gaining popularity. The aim of this study was to compare the incidence of postoperative pancreatic fistula (POPF) after minimally invasive versus open procedures.
MATERIALS AND METHODS
Following the PRISMA statement, literature research was conducted focusing on papers comparing the incidence of POPF after open pancreaticoduodenectomy (OPD) versus minimally invasive pancreaticoduodenectomy (MIPD).
RESULTS
Twenty-one papers were included in this meta-analysis, for a total of 4,448 patients. A total of 2,456 patients (55.2%) underwent OPD, while 1,992 (44.8%) underwent MIPD. Age, ASA score III patients, incidence of pancreatic ductal adenocarcinoma and duct diameter were significantly lower in the MIPD group. No statistically significant differences were found between the OPD and MIPD regarding the incidence of major complications (15.6% vs. 17.0%, respectively, p=0.55), mortality (3.7% vs. 2.4%, p=0.81), and POPF rate (14.3% vs. 12.9%, p=0.25).
CONCLUSION
MIPD and OPD had comparable rates of postoperative complications, postoperative mortality, and POPF.
Topics: Humans; Minimally Invasive Surgical Procedures; Pancreas; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications
PubMed: 35790274
DOI: 10.21873/anticanres.15817