Delayed introduction of sirolimus in paediatric intestinal transplant recipients: indications and long‐term benefits

Abstract

To review our experience using sirolimus in a single centre paediatric intestinal transplantation cohort. Intestinal transplant patients with more than 3 months follow-up were divided into two groups according to their immunosuppression regimen: tacrolimus, (TAC group, n = 45 grafts) or sirolimus (SRL group, n = 38 grafts), which included those partially or completely converted from tacrolimus to sirolimus. The indications to switch were tacrolimus side effects and immunological complications. Survival and complications were retrospectively analysed comparing both groups. SRL was introduced 9 months (0 months-16.9 years) after transplant. The main cause for conversion was worsening renal function (45%), followed by haemolytic anaemia (21%) and graft-versus-host-disease (16%). Both groups showed a similar overall patient/graft survival (P = 0.76/0.08) and occurrence of rejection (24%/17%, P = 0.36). Immunological complications did not recur after conversion. Renal function significantly improved in most SRL patients. After a median follow-up of 65.17 months, 28/46 survivors were on SRL, 26 with monotherapy, with good graft function. Over one-third of our patients eventually required SRL conversion that allowed to improve their kidney function and immunological events, without entailing additional complications or survival impairment. Further trials are warranted to clarify the potential improvement of the standard tacrolimus maintenance by sirolimus conversion or addition.

Antibody-removal therapies for de novo DSA in pediatric intestinal recipients: Why, when, and how? A single-center experience

“…Different induction protocols were used as previously reported ( 12 ) ( Table 1 ). Maintenance immunosuppression was based on tacrolimus (blood levels of 10–15 ng/ml until the 3rd month and 5–10 ng/ml from the 3rd month onward).…”

“…When induction was made with basiliximab, corticosteroids were also required as part of maintenance therapy. Sirolimus (2 mg/m 2 daily with blood levels in the 5–10 ng/ml range) was used according to what was previously reported by our group ( 12 ) in 40 transplants (8 combined with tacrolimus and 32 in monotherapy).…”

Update on immunosuppressive strategies in intestinal transplantation

“…Recently, the mammalian target of rapamycin (mTOR) inhibitor sirolimus and the antimetabolite mycophenolate mofetil (MMF) have been added to some protocols. Sirolimus is increasingly used at later posttransplant timepoints, especially because of concern for early wound complications, and has recently shown advantages for controlling rejection with lower risk of renal injury, hemolytic anemia, neuroroxicity, thrombotic microangiopathy, and potentially GVHD [19 ▪ ]. MMF has also been employed to reduce nephrotoxicity associated with long-term use of calcineurin inhibitors.…”

Precision sirolimus dosing in children: The potential for model-informed dosing and novel drug monitoring

“…In addition, the European Medicines Agency (EMA) approved Rapamune ® for prophylaxis of organ rejection in adults at low to moderate immunological risk receiving a renal transplant and for treatment of patients with sporadic lymphangioleiomyomatosis with moderate lung disease or declining lung function ( EMA, 2022 ). Over the past 20 years since these initial approvals, sirolimus has expanded to treat children undergoing heart ( Rossano et al, 2017 ), hematopoietic cell ( Monagel et al, 2021 ), intestine ( Andres et al, 2021 ), liver ( Hendrickson et al, 2019 ), or lung transplant ( Hayes et al, 2014 ). Furthermore, children with vascular anomalies are treated with sirolimus ( Mizuno et al, 2017c ).…”