Conversion to Mycophenolate Mofetil Monotherapy in Liver Recipients: Calcineurin Inhibitor Levels are Key

Abstract: The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow- up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.

Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor / Tratamiento de la enfermedad linfoproliferativa post-trasplante renal con Rituximab y conversión a inhibidor m-TOR

Abstract Background: Post-transplantation lymphoproliferative disorders are serious complications of organ transplantation which treatment is not yet standardized. Objective: To describe the clinical response, overall and graft survival of patients in our center with this complication after kidney transplantation, which received rituximab as part of their treatment as well as conversion to m-TOR. Methods: Retrospective study, which included patients, diagnosed with post-transplant lymphoproliferative disorders after kidney transplantation from January 2011 to July 2014. Results: Eight cases were found with a wide spectrum of clinical presentations. Most had monomorphic histology, 85% were associated with Epstein-Barr virus, 25% of patients had tumor involvement of the renal graft, and 12.5% ​​had primary central nervous system lymphoma. All patients were managed with reduction of immunosuppression, conversion to m-TOR (except one who lost the graft at diagnosis) and rituximab-based therapy. The overall response rate was 87.5% (62.5% complete response, 25% partial response). Survival was 87.5% with a median follow-up of 34 months. An additional patient lost the graft, with chronic nephropathy already known. All the remaining patients had stable renal function. Conclusions: There are no standardized treatment regimens for lymphoproliferative disorders after kidney transplantation, but these patients can be managed successfully with reduction of immunosuppression, conversion to m-TOR and rituximab-based schemes.

Resumen Antecedente: La enfermedad linfoproliferativa post-trasplante es una complicación grave del trasplante de órganos cuyo tratamiento aún no se encuentra estandarizado. Objetivo: Describir la respuesta clínica, supervivencia global y del injerto en pacientes con esta complicación post trasplante renal en nuestro centro y que recibieron rituximab como parte de su tratamiento y la conversión a m-TOR. Métodos: Estudio retrospectivo que incluyó pacientes con diagnóstico de enfermedad linfoproliferativa postrasplante renal entre enero de 2011 y julio de 2014. Resultados: Se encontraron ocho casos, con presentaciones clínicas variables. La mayoría correspondieron a histología monomórfica, en 85% se asoció con virus de Epstein-Barr, 25% de los pacientes tenían compromiso tumoral del injerto renal y 12.5% linfoma primario de sistema nervioso central. Todos los pacientes se manejaron con reducción de inmunosupresión, conversión a m-TOR (excepto uno que perdió el injerto al diagnóstico) y tratamiento basado en rituximab. La tasa de respuesta global fue del 87.5% (62.5% respuesta completa, 25% respuesta parcial). La supervivencia fue del 87.5% con una mediana de seguimiento de 34 meses. Un paciente adicional perdió el injerto renal, con nefropatía crónica ya conocida. Los pacientes restantes con función renal estable. Conclusiones: No existen esquemas estandarizados de tratamiento para la enfermedad linfoproliferativa post-trasplante renal, pero estos pacientes pueden ser manejados de forma exitosa con reducción de la inmunosupresión, conversión a m-TOR y esquemas basados en rituximab.

Prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation

OBJECTIVE: Chronic rejection remains a major cause of graft failure with indication for re-transplantation. The incidence of chronic rejection remains high in the pediatric population. Although several risk factors have been implicated in adults, the prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation are not known. Hence, the current study aimed to determine the factors involved in the progression or reversibility of pediatric chronic rejection by evaluating a series of chronic rejection cases following liver transplantation. METHODS: Chronic rejection cases were identified by performing liver biopsies on patients based on clinical suspicion. Treatment included maintaining high levels of tacrolimus and the introduction of mofetil mycophenolate. The children were divided into 2 groups: those with favorable outcomes and those with adverse outcomes. Multivariate analysis was performed to identify potential risk factors in these groups. RESULTS: Among 537 children subjected to liver transplantation, chronic rejection occurred in 29 patients (5.4%). In 10 patients (10/29, 34.5%), remission of chronic rejection was achieved with immunosuppression (favorable outcomes group). In the remaining 19 patients (19/29, 65.5%), rejection could not be controlled (adverse outcomes group) and resulted in re-transplantation (7 patients, 24.1%) or death (12 patients, 41.4%). Statistical analysis showed that the presence of ductopenia was associated with worse outcomes (risk ratio=2.08, p=0.01). CONCLUSION: The presence of ductopenia is associated with poor prognosis in pediatric patients with chronic graft rejection.