Mesenchymal stromal cells as treatment or prophylaxis for acute or chronic graft-versus-host disease in haematopoietic stem cell transplant (HSCT) recipients with a haematological condition.
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SUBMITTER: Fisher SA
PROVIDER: S-EPMC6353308 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSystematic studies pertaining to the emergence of resistance during therapy of Pseudomonas aeruginosa bloodstream infections (BSIs) in haematopoietic cell transplant (HCT) recipients and haematological malignancy (HM) patients are lacking.ObjectivesTo determine how frequently non-susceptibility emerges during therapy of P. aeruginosa BSIs and to compare these findings with non-HCT/HM patients.Patients and methodsP. aeruginosa BSIs that occurred at our institution between 1 July 2012 and 31 October 2019 in HCT/HM patients and non-HCT/HM patients were identified. Episodes in which bacteraemia persisted while on appropriate therapy ('persistent BSI') were evaluated for emergence of non-susceptibility during therapy.ResultsIn total, 96 BSI episodes among 86 HCT/HM patients were analysed. Eight persistent BSI episodes (8.3%) occurred in eight patients (9.3%). Repeat susceptibility testing was performed in seven (87.5%) of these episodes. Non-susceptibility to the treatment agent emerged in five (71.4%) episodes and to any antipseudomonal agent in seven (100%) episodes. The 21 day mortality rate associated with persistent BSI was 87.5% (seven of eight), and it was 80% (four of five) among persistent BSI episodes in which non-susceptibility to the treatment agent emerged on therapy. Non-susceptibility to any antipseudomonal agent during persistent BSI emerged significantly more frequently in HCT/HM patients compared with non-HCT/HM patients.ConclusionsNon-susceptibility emerges frequently during persistent P. aeruginosa BSIs in HCT/HM patients, and this is associated with a high mortality rate. Our findings have implications for the management of persistent P. aeruginosa BSIs in these patients. Larger studies are needed to confirm and expand on our findings.
| S-EPMC8519295 | biostudies-literature
Project description:Despite excellent short-term graft survival after renal transplantation, the long-term graft outcome remains compromised. It has become evident that a combination of sustained alloreactivity and calcineurin-inhibitor- (CNI-) related nephrotoxicity results in fibrosis and consequently dysfunction of the graft. New immunosuppressive regimens that can minimize or eliminate side effects, while maintaining efficacy, are required to improve long-term graft survival. In this perspective mesenchymal stromal cells (MSCs) are an interesting candidate, since MSCs have immunosuppressive and regenerative properties. The first clinical trials with MSCs in renal transplantation showed safety and feasibility and displayed promising results. Recently, the first phase II studies have been started. One of the most difficult and challenging aspects in those early phase trials is to define accurate endpoints that can measure safety and efficacy of MSC treatment. Since both graft losses and acute rejection rates declined, alternative surrogate markers such as renal function, histological findings, and immunological markers are used to measure efficacy and to provide mechanistic insight. In this review, we will discuss the current status of MSCs in renal transplantation with a focus on the endpoints used in the different experimental and clinical studies.
| S-EPMC4518147 | biostudies-literature
Project description:BackgroundGraft-versus-host disease (GvHD) is the main life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Thirty to 80% of GvHD patients do not respond to first-line treatment and a second-line treatment is not universally established. Based on their immunomodulatory properties, mesenchymal stromal cells (MSC) have been proposed for the prevention and the treatment of GvHD in patients undergoing HSCT. Unfortunately, previous studies reported conflicting results regarding the prophylactic and therapeutic effects of MSC for GvHD. Consequently, we carried out a meta-analysis to clarify whether MSC administration can improve the dismal outcome of these patients.MethodsWe carried out a systematic review and selected studies (2004-2019) reporting data about the administration of allogeneic MSC for the prevention (n = 654 patients) or treatment of acute (n = 943 patients) or chronic (n = 76 patients) GvHD after HSCT. Our primary outcome was overall survival at the last follow-up. The secondary outcomes were the response and development of GvHD. Subgroup analyses included age, MSC dose, first infusion day after HSCT, number of organs and organ-specific involvement, acute GvHD grade (I-IV), and chronic GvHD grade (limited or extensive).ResultsPatients infused with MSC for GvHD prophylaxis showed a 17% increased overall survival (95% CI, 1.02-1.33) and a reduced incidence of acute GvHD grade IV (RR = 0.22; 95% CI, 0.06-0.81) and chronic GvHD (RR = 0.64; 95% CI, 0.47-0.88) compared with controls. Overall survival of acute GvHD patients (0.50; 95% CI, 0.41-0.59) was positively correlated with MSC dose (P = 0.0214). The overall response was achieved in 67% (95% CI, 0.61-0.74) and was complete in 39% (95% CI, 0.31-0.48) of acute patients. Organ-specific response was higher for the skin. Twenty-two percent (95% CI, 0.16-0.29) of acute patients infused with MSC developed chronic GvHD. Sixty-four percent (95% CI, 0.47-0.80) of chronic patients infused with MSC survived; the overall response was 66% (95% CI, 0.55-0.76) and was complete in 23% (95% CI 0.12-0.34) of patients.ConclusionsOur meta-analysis indicates that allogeneic MSC could be instrumental for the prophylaxis and treatment of GvHD. Future trials should investigate the effect of the administration of MSC as an adjuvant therapy for the treatment of patients with GvHD from the onset of the disease.
| S-EPMC7027118 | biostudies-literature
Project description:Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome that complicates hematopoietic stem cell transplant (HSCT). Morbidity and mortality from TA-TMA remain high, making prevention critical. We describe our retrospective single-center experience of TA-TMA after pediatric allogeneic HSCT and present a novel pre-HSCT risk-stratification system and prophylaxis regimen. From January 2012 through October 2019, 257 patients underwent 292 allogeneic HSCTs. Prospective risk stratification was introduced in December 2016. High-risk (HR) patients were treated with combination prophylaxis with eicosapentaenoic acid and N-acetylcysteine. The 1-year cumulative incidence of TA-TMA was 6.3% (95% confidence interval [CI], 3.2-9.4). Age ≥10 years, myeloablative conditioning with total body irradiation, HLA mismatch, diagnosis of severe aplastic anemia or malignancy, prior calcineurin inhibitor exposure, and recipient cytomegalovirus seropositivity were found to be pre-HSCT risk factors for development of TA-TMA. Before routine prophylaxis, TA-TMA rates were significantly different between the HR and standard-risk groups, at 28.2% (95% CI, 0-12.7) vs 3.2% (0.1-6.3), respectively (P < .001). After introduction of prophylaxis, the 1-year cumulative incidence of TA-TMA in the HR group decreased to 4.5% (95% CI, 0-13.1; P = .062, compared with the incidence before prophylaxis). Multicenter pediatric studies are needed to validate these risk criteria and to confirm the efficacy of the prophylactic regimen.
| S-EPMC8095147 | biostudies-literature
Project description:Guidelines recommend targeted antifungal prophylaxis for liver transplant (LT) recipients based on tiers of risk, rather than universal prophylaxis. The feasibility and efficacy of tiered, targeted prophylaxis is not well established. We performed a retrospective study of LT recipients who received targeted prophylaxis (n = 145; voriconazole [VORI; 54%], fluconazole [8%], no antifungal [38%]) versus universal VORI prophylaxis (n = 237). Median durations of targeted and universal prophylaxis were 11 and 6 days, respectively (p < 0.0001). The incidence of invasive fungal infections (IFIs) in targeted and universal groups was 6.9% and 4.2% (p = 0.34). Overall, intra-abdominal candidiasis (73%) was the most common IFI. Posttransplant bile leaks (p = 0.001) and living donor transplants (p = 0.04) were independent risk factors for IFI. IFIs occurred in 6% of high-risk transplants who received prophylaxis and 4% of low-risk transplants who did not receive prophylaxis (p = 1.0). Mortality rates (100 days) were 10% (targeted) and 7% (universal) (p = 0.26); attributable mortality due to IFI was 10%. Compliance with prophylaxis recommendations was 97%. Prophylaxis was discontinued for toxicity in 2% of patients. Targeted antifungal prophylaxis in LT recipients was feasible and safe, effectively prevented IFIs and reduced the number of patients exposed to antifungals. Bile leaks and living donor transplants should be considered high-risk indications for prophylaxis.
| S-EPMC4365781 | biostudies-literature
Project description:Recipients of a haematopoietic stem cell transplantation (HSCT) may experience issues in medication adherence (MA) when discharged. The primary aim of this review was to describe the oral MA prevalence and the tools used to evaluate it among these patients; the secondary aims were to summarise factors affecting medication non-adherence (MNA), interventions promoting MA, and outcomes of MNA. A systematic review (PROSPERO no. CRD42022315298) was performed by searching the Cumulative Index of Nursing and Allied Health (CINAHL), Cochrane Library, Excerpta Medica dataBASE (EMBASE), PsycINFO, PubMed and Scopus databases, and grey literature up to May 2022 by including (a) adult recipients of allogeneic HSCT, taking oral medications up to 4 years after HSCT; (b) primary studies published in any year and written in any language; (c) with an experimental, quasi-experimental, observational, correlational, and cross-sectional design; and (d) with a low risk of bias. We provide a qualitative narrative synthesis of the extracted data. We included 14 studies with 1049 patients. The median prevalence of MA was 61.8% and it has not decreased over time (immunosuppressors 61.5% [range 31.3-88.8%] and non-immunosuppressors 65.2% [range 48-100%]). Subjective measures of MA have been used most frequently (78.6%) to date. Factors affecting MNA are younger age, higher psychosocial risk, distress, daily immunosuppressors, decreased concomitant therapies, and experiencing more side effects. Four studies reported findings about interventions, all led by pharmacists, with positive effects on MA. Two studies showed an association between MNA and chronic graft-versus-host disease. The variability in adherence rates suggests that the issues are relevant and should be carefully considered in daily practice. MNA has a multifactorial nature and thus requires multidisciplinary care models.
| S-EPMC10177142 | biostudies-literature
Project description:Mesenchymal stromal cells (MSC) may serve as an attractive therapy in renal transplantation due to their immunosuppressive and reparative properties. While most studies have used autologous MSCs, allogeneic MSCs offer the advantage of immediate availability for clinical use. This is of major importance for indications where instant treatment is needed, for example allograft rejection or calcineurin inhibitor toxicity. Clinical studies using allogeneic MSCs are limited in number. Although these studies showed no adverse reactions, allogeneic MSCs could possibly elicit an anti-donor immune response, which may increase the incidence of rejection and impact the allograft survival in the long term. These safety issues should be addressed before further studies are planned with allogeneic MSCs in the solid organ transplant setting.10 renal allograft recipients, 18-75 years old, will be included in this clinical phase Ib, open label, single center study. Patients will receive two doses of 1.5 × 10(6) per/kg body weight allogeneic bone marrow derived MSCs intravenously, at 25 and 26 weeks after transplantation, when immune suppression levels are reduced. The primary end point of this study is safety by assessing biopsy proven acute rejection (BPAR)/graft loss after MSC treatment. Secondary end points, all measured before and after MSC infusions, include: comparison of fibrosis in renal biopsy by quantitative Sirius Red scoring; de novo HLA antibody development and extensive immune monitoring; renal function measured by cGFR and iohexol clearance; CMV and BK infection and other opportunistic infections.This study will provide information on the safety of allogeneic MSC infusion and its effect on the incidence of BPAR/graft loss.NCT02387151.
| S-EPMC4632480 | biostudies-literature
Project description:IntroductionPatients receiving a haematopoietic stem cell transplant (HSCT) are subjected to complex oral medications based on prophylactic and immunosuppressive treatments. Adherence to medication plays a role in survival, and medication non-adherence (MNA) is closely associated with graft-versus-host disease and other complications. The aim of this systematic review is to summarise the available evidence regarding prevalence rates of medication adherence, the risk factors of MNA, the effectiveness of interventions to increase medication adherence and the outcomes associated with MNA.Methods and analysisWe designed a systematic review according to the Joanna Briggs Institute methodology. We will search the Cochrane Library and the CINAHL, EMBASE, MEDLINE via PubMed, PsycINFO and Scopus databases. We will include published and unpublished primary studies: (a) on humans, from inception until 10 May 2022; (b) written in any language; (c) experimental (randomised and non-randomised), observational (prospective, retrospective cohort and case-control), correlational, cross-sectional and longitudinal; and (d) with a low risk of bias, according to the quality assessment we perform. We will exclude secondary and qualitative studies, protocols, publications without original data, including paediatrics or related to autologous HSCT. The primary outcome will be the prevalence of oral medication adherence; the secondary outcomes will be the risk factors of MNA, the interventions aimed at increasing medication adherence and the outcomes of MNA. Two researchers will independently screen the eligible studies, then extract and describe the data. Disagreements will be resolved by a third researcher. We will provide a qualitative narrative synthesis of the findings.Ethics and disseminationEthical approval is not required given that previously published studies will be used. We will disseminate the findings through conference presentations and publications in international peer-reviewed scientific journals.Prospero registration numberCRD42022315298.
| S-EPMC9717329 | biostudies-literature
Project description:High-density lipoprotein (HDL) particles are involved in the protection against cardiovascular disease by promoting cholesterol efflux, in which accumulated cholesterol is removed from macrophage foam cells. We investigated whether HDL cholesterol efflux capacity is associated with cardiovascular mortality, all-cause mortality, and graft failure in a cohort of renal transplant recipients (n=495, median follow-up 7.0 years). Cholesterol efflux capacity at baseline was quantified using incubation of human macrophage foam cells with apolipoprotein B-depleted plasma. Baseline efflux capacity was not different in deceased patients and survivors (P=0.60 or P=0.50 for cardiovascular or all-cause mortality, respectively), whereas recipients developing graft failure had lower efflux capacity than those with functioning grafts (P<0.001). Kaplan-Meier analysis demonstrated a lower risk for graft failure (P=0.004) but not cardiovascular (P=0.30) or all-cause mortality (P=0.31) with increasing gender-stratified tertiles of efflux capacity. Cox regression analyses adjusted for age and gender showed that efflux capacity was not associated with cardiovascular mortality (hazard ratio [HR], 0.89; 95% confidence interval [95% CI], 0.67 to 1.19; P=0.43). Furthermore, the association between efflux capacity and all-cause mortality (HR, .79; 95% CI, 0.63 to 0.98; P=0.031) disappeared after further adjustment for potential confounders. However, efflux capacity at baseline significantly predicted graft failure (HR, 0.43; 95% CI, 0.29 to 0.64; P<0.001) independent of apolipoprotein A-I, HDL cholesterol, or creatinine clearance. In conclusion, this prospective study shows that cholesterol efflux capacity from macrophage foam cells is not associated with cardiovascular or all-cause mortality but is a strong predictor of graft failure independent of plasma HDL cholesterol levels in renal transplant recipients.
| S-EPMC4731105 | biostudies-literature
Project description:Delayed graft function (DGF) complicates kidney allograft outcomes in the immediate post-transplantation period. We hypothesized that in hemodialysis patients more severe anemia, iron deficiency, the requirement for higher doses of erythropoietin-stimulating agents (ESA), or blood transfusions prior to transplantation are associated with higher risk of DGF.Linking five-yr hemodialysis patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 11 836 hemodialysis patients. Using logistic regression analyses we examined the association between pre-transplant parameters and post-transplant DGF.Patients were 49 ± 14 (mean ± SD) yr old and included 38% women, 27% blacks, and 26% diabetics. After adjusting for relevant covariates, pre-transplant blood transfusion was associated with 33% higher DGF risk (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 1.19-1.48); and each 5000 U/wk increase of pre-transplant ESA dose with 5% higher DGF (OR = 1.05; 95% CI: 1.02-1.09). Compared to pre-transplant blood hemoglobin of 12-12.99 g/dL, there was 25% higher risk of DGF with blood hemoglobin 10-10.99 g/dL (OR = 1.25; 95% CI: 1.01-1.55), whereas blood hemoglobin ?13 g/dL exhibited 15% higher risk of DGF (OR = 1.15; 95% CI: 0.98-1.34).Pre-transplant blood transfusion, higher ESA dose, and either high or low blood hemoglobin but not iron markers are associated with higher risk of DGF.
| S-EPMC4571494 | biostudies-literature