Efficacy and Tolerability of Sirolimus in Lymphangioleiomyomatosis Patients after Lung Transplantation: Single-Center Experience in Japan

Abstract

<h3>Purpose</h3> Lung transplantation (LTx) is an effective treatment for patients with end-stage pulmonary lymphangioleiomyomatosis (LAM). However, native lung-related complications, such as chylothorax, chylous sputum, and native lung hyperinflation, can develop after a single LTx. LAM lesion recurrence in transplanted lungs and abdominal LAM lesions may also occur post-LTx. Further, while sirolimus therapy can be used to treat these complications, its efficacy and tolerability in patients with LAM after LTx remain unclear. This study aimed to evaluate the effect of sirolimus on post-LTx LAM complications. <h3>Methods</h3> We retrospectively reviewed the records of LTx recipients who received sirolimus for treating post-LTx LAM complications from March 2000 to December 2019. <h3>Results</h3> Of the 40 patients who underwent LTx for LAM treatment, eight underwent sirolimus treatment for post-LTx LAM complications. Two patients exhibited chylous sputum; two, chylous ascites; one, chylothorax; one, native lung hyperinflation; one, LAM recurrence in the transplanted lung; and one, angiomyolipoma. Patients' immunosuppressive regimen consisting of tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids was not changed, but the target trough level of TAC was reduced with the baseline levels of TAC and sirolimus being 5 ng/mL each. Sirolimus was discontinued for one patient because nausea occurred soon after the first dose. LAM lesions improved or were suppressed in six patients (Figure 1). The forced expiratory volume at 1 s post-sirolimus administration was stable (Figure 2). Acute rejection and infection were not observed, but one patient underwent a second LTx on the contralateral side due to chronic lung allograft dysfunction. <h3>Conclusion</h3> Providing sirolimus immunosuppressive therapy after LTx for LAM treatment can be effective in managing post-LTx LAM complications and may be acceptable when combined with TAC, MMF, and steroids.