Everolimus Plus Mycophenolate Mofetil as Initial Immunosuppression in Liver Transplantation

Jiménez‐Pérez, Miguel; Grande, Rocío González; Muñoz, F.J. Rando; Lombardo, J. de la Cruz; Suárez, Miguel Ángel; Aguilar, José Luis Fernández; Daga, J.A. Pérez; Santoyo-Santoyo, Julio; Gonzalez, Rafael; López, J.M. Rodrigo

doi:10.1016/j.transproceed.2014.11.005

Cited by 14 publications

(26 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, novel immunosuppressive regimens such as CSA/RAD and RAD/MMF were evaluated for the first time in multivariate analyses for their potential to reduce graft rejection in a nonmyeloablative/RIC HSCT model. In accordance with previous results from solid organ transplantations, our findings reveal a similar rejection rate with CSA/RAD and a nonsignificantly increased rejection rate with RAD/MMF compared with standard immunosuppression (ie, CSA/MMF) [39,40].…”

Section: Discussionsupporting

confidence: 92%

Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model

Lange

Steder

Glass

et al. 2016

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P < .001) and low TNC cell count (P = .044) were identified as significant independent risk factors for graft rejection. Peripheral blood mononuclear cell chimerism ≥30% (P = .008) and granulocyte chimerism ≥70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of blood chimerism at 4 weeks post-HSCT was predictive of long-term engraftment in the canine HSCT model.

show abstract

Section: Discussionsupporting

confidence: 92%

Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model

Lange

Steder

Glass

et al. 2016

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

show abstract

“…The use of EVR with mycophenolic acid derivatives without CNIs may be another renal-protective strategy used in liver transplant recipients. 21 Fourth, there were high rates of discontinuation in both the EVR + rTAC and TAC-C groups (49.2% vs 32.1%). The higher discontinuation rate in the EVR + rTAC arm might be attributable to the fact that this is the experimental arm and so clinicians would have been less familiar with this treatment in comparison to the standard treatment.…”

Section: Discussionmentioning

confidence: 90%

Effect of Early Everolimus-Facilitated Reduction of Tacrolimus on Efficacy and Renal Function in De Novo Liver Transplant Recipients

et al. 2017

View full text Add to dashboard Cite

BackgroundA recent randomized phase III study of 719 de novo liver transplant recipients showed that early everolimus plus reduced-dose tacrolimus (EVR + rTAC) led to significantly better kidney function than standard TAC (TAC-C), without compromising efficacy. In that study, patients from North America (n = 211) had increased risk factors for posttransplant renal insufficiency at study start, relative to patients from Europe and rest of world (eg, worse renal function, more diabetes, older age).MethodsA post hoc analysis was performed to assess whether these regional disparities affected study outcomes in North American patients.ResultsIn this subpopulation, estimated glomerular filtration rates at randomization were higher in TAC-C over EVR + rTAC (76.4 vs 69.3 mL/min per 1.73 m2). Mean changes in estimated glomerular filtration rate values (mL/min per 1.73 m2) favored EVR + rTAC over TAC-C at months 12 (+3.7 vs −4.5; P = 0.032), 24 (+2.7 vs −6.6; P = 0.042), and 36 (+4.3 vs −8.1; P = 0.059). The composite efficacy endpoint of treated biopsy-proven acute rejection, graft loss, or death was 10.9%, 14.1%, and 14.1% for EVR + rTAC and 13.1%, 17.2%, and 19.3% for TAC-C at months 12, 24, and 36, respectively.ConclusionsAlthough the North American cohort had more comorbidities, results were consistent with the overall population for efficacy and renal function.

show abstract

“… 3 As the potency of MMF for IS is not high enough, 2 MMF monotherapy was rarely attempted within the first year of LT at our institution. Recently, the combination of MMF and everolimus together with very low-dose tacrolimus has been selectively attempted in recipients showing progressive renal dysfunction during the first year of LT. 19 20 21 22 An analysis of high-volume data from the Scientific Registry of Transplant Recipients has revealed that mTOR inhibitor-based IS therapy is associated with improved survival after LT in recipients with HCC; however, it has also revealed a trend toward lower survival rates in non-HCC recipients. 23 …”

Section: Discussionmentioning

confidence: 99%

A cross-sectional analysis of long-term immunosuppressive regimens after liver transplantation at Asan Medical Center: Increased preference for mycophenolate mofetil

Hwang

Ahn

Kim

et al. 2018

Ann Hepatobiliary Pancreat Surg

View full text Add to dashboard Cite

Backgrounds/AimsLong-term immunosuppression regimens after liver transplantation (LT) are rarely reported in detail. We aimed to provide information on actual long-term immunosuppression regimens through this cross-sectional study.MethodsOur institutional LT database was searched for adult patients who underwent primary LT operation from 2000 to 2016. We identified 3620 live recipients with actual information on immunosuppressive agent use for 1–17 years.ResultsThe study cohort was divided into 7 groups according to posttransplantation period. The immunosuppressive agents used at the cross-sectional review period were tacrolimus in 2884 (79.7%), cyclosporine in 445 (12.3%), mycophenolate mofetil in 2007 (55.4%), and everolimus in 138 (3.8%) recipients. There was no marked difference in immunosuppressive agent use according to pretransplantation liver malignancy or type of LT operation. Tacrolimus, cyclosporine, mycophenolate mofetil, and everolimus were used in 97.4%, 1.8%, 60.9%, and 9.2%, respectively, in the year 2 group; 94.1%, 3.9%, 51.6%, and 8.3%, respectively, in the year 3 group; 87.3%, 8.4%, 68.9%, and 4.8%, respectively, in the year 4–5 group; 78.2%, 12.9%, 64.6%, and 3.0%, respectively, in the year 6–7 group; 76.9%, 10.8%, 58.8%, and 2.4%, respectively, in the year 8–10 group; 66.7%, 22.4%, 43.4%, and 1.5%, respectively, in the year 11–15 group; and 73.8%, 15.4%, 32.9%, and 1.7%, respectively, in the year ≥15 group.ConclusionsTacrolimus and mycophenolate mofetil are the primary immunosuppressive agents after LT, and the indications for everolimus have started to increase at our institution. We believe our results will help establish tailored long-term immunosuppression regimens.

show abstract

Everolimus Plus Mycophenolate Mofetil as Initial Immunosuppression in Liver Transplantation

Cited by 14 publications

References 14 publications

Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model

Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model

Effect of Early Everolimus-Facilitated Reduction of Tacrolimus on Efficacy and Renal Function in De Novo Liver Transplant Recipients

A cross-sectional analysis of long-term immunosuppressive regimens after liver transplantation at Asan Medical Center: Increased preference for mycophenolate mofetil

Contact Info

Product

Resources

About