Lung Transplantation for Lymphangioleiomyomatosis in Japan

Abstract

Background: Lung transplantation has been established as the definitive treatment option for patients with advanced lymphangioleiomyomatosis (LAM). However, the prognosis after registration and the circumstances of lung transplantation with sirolimus therapy have never been reported.

Methods: In this national survey, we analyzed data from 98 LAM patients registered for lung transplantation in the Japan Organ Transplantation Network.

Results: Transplantation was performed in 57 patients as of March 2014. Survival rate was 86.7% at 1 year, 82.5% at 3 years, 73.7% at 5 years, and 73.7% at 10 years. Of the 98 patients, 21 had an inactive status and received sirolimus more frequently than those with an active history (67% vs. 5%, p<0.001). Nine of twelve patients who remained inactive as of March 2014 initiated sirolimus before or while on a waiting list, and remained on sirolimus thereafter. Although the statistical analysis showed no statistically significant difference, the survival rate after registration tended to be better for lung transplant recipients than for those who awaited transplantation (p = 0.053).

Conclusions: Lung transplantation is a satisfactory therapeutic option for advanced LAM, but the circumstances for pre-transplantation LAM patients are likely to alter with the use of sirolimus.

Fig 1. Kaplan-Meier calculated survival rate after lung transplantation for 57 patients with LAM.

The median follow-up period was 1,085 days. The probability of survival at 1, 3, 5 and 10 years after lung transplantation was 86.7%, 82.5%, 73.7% and 73.7%, respectively.

Fig 2. Illustration of the periods of inactive status and sirolimus treatment while on the transplantation waiting list.

A. Eight of 21 LAM patients with a history of inactive status had received lung transplants. Five of eight patients had a period during which they had been on the sirolimus treatment (we could not confirm the period of time in case 3*). The reason why a patient had been inactive is indicated at the right end of each illustration by: A, anxiety and fear about transplantation; C, comorbidity (cases 6 and 8, psychiatric disorder and case 3, thyroid tumor); F, family matter; M, participated in the MILES trial; NA, not available; and S, on sirolimus treatment. Although the cases 1 and 7 participated in the MILES trial, they were in the placebo group; the case 7 took sirolimus after the MILES trial. The clinical courses of cases 2, 4, 5, and 7 who took sirolimus, but their clinical courses were not stabilized sufficiently. B. Of twelve patients who were in an inactive status as of March 2014, nine initiated sirolimus treatment before registration (cases 2 and 6) or while on a waiting list (cases 3, 4, 5, 8, 9, 11, and 12). The reason for being inactive is presented with the same manner as in Fig 2A (A and M); S(S) indicates that a patient has been on sirolimus treatment and respiratory condition has improved or been stabilized.