Favorable survival even with high disease‐specific complication rates in lymphangioleiomyomatosis after lung transplantation—long‐term follow‐up of a Japanese center

Abstract

Background: Lung transplantation (LT) is a reliable therapeutic option for end-stage pulmonary lymphangioleiomyomatosis (LAM). Long-term outcome of LAM recipients after LT remains unknown. The aim of this study was to describe the outcomes of LT for LAM with a long-term follow-up, comparing those for other diseases in the same period. Methods: We retrospectively reviewed consecutive 145 LT recipients between 1998 and 2015 at Okayama University Hospital with minimum 3-year follow-up. Results: Twelve LAM recipients including nine sporadic-LAM and three tuberous sclerosis complex -LAM were identified. Nine of 12 underwent bilateral LT including four living-donor lobar LT. There was no significant difference in overall survival between the two groups. (P = 0.15). Chronic lung allograft dysfunction free survival rate in LAM compared with other diseases tended to be better (P = 0.058). However, the rate of requiring hemodialysis was significantly higher in LAM recipients than in the recipients of other diseases (P = 0.047). Notably, 8 of 12 (67%) LAM patients encountered LAM-related complication including chylothorax and pneumothorax, seven (58%) had proliferative diseases consisting of renal angiomyolipoma and recurrent LAM. Nine patients required mTOR inhibitors for LAM-related problems, contributing to improved control of LAM-related problems. While all nine recipients of bilateral LT have still survived, two patients died of diseases in their native lungs and one required re-LT among three recipients of single LT. Conclusion: Although the rates of LAM-related complications were unexpectedly high in the long term, LT is a feasible therapeutic option for patients with advanced pulmonary LAM. K E Y W O R D S lung transplantation, lymphangioleiomyomatosis, mTOR inhibitor | 117 KUROSAKI et Al.

Ultra-rare cystic disease

“…Positive outcomes were also reported by two retrospective studies in a German and a Japanese centre even if the latter found a high rate of LAM-related complications in long-term follow-up (e.g. chylothorax, pneumothorax and LAM recurrence) [71,72].…”

Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation

“…Lung transplant for LAM is relatively rare; however, it is associated with better post-transplant survival compared to other advanced lung diseases. (1,(303)(304)(305)(306)(307) Fewer patients with LAM have required lung transplant since the standardized use of mTOR inhibitors as treatment, but it remains an indication for those with severely abnormal lung function (FEV 1 < 30%), exertional dyspnea (NYHA class III or IV), or hypoxemia at rest. (303)(304)(305)(306)(308)(309)(310)(311)(312)(313)(314)(315) While disease recurrence does occur post-transplant, it does not appear to limit survival.…”

“…(1,(303)(304)(305)(306)(307) Fewer patients with LAM have required lung transplant since the standardized use of mTOR inhibitors as treatment, but it remains an indication for those with severely abnormal lung function (FEV 1 < 30%), exertional dyspnea (NYHA class III or IV), or hypoxemia at rest. (303)(304)(305)(306)(308)(309)(310)(311)(312)(313)(314)(315) While disease recurrence does occur post-transplant, it does not appear to limit survival. (303,304,309,311,(316)(317)(318) Where organ availability allows, bilateral lung transplant may be favored given the risk of post-transplant pneumothorax in the native lung; however, single lung transplant confers similar overall survival based on limited data.…”

“…(303,304,309,311,(316)(317)(318) Where organ availability allows, bilateral lung transplant may be favored given the risk of post-transplant pneumothorax in the native lung; however, single lung transplant confers similar overall survival based on limited data. (306,312,314,319). Lung transplant for LAM may be challenging surgically due to the high prevalence of adhesions resulting from the management of pleural complications prior to transplant.…”

Indications for Lung Transplantation and Patient Selection

“…An important issue to consider is that these patients usually have had a prior pleural procedure, which can cause a large amount of bleeding during transplantation. The use of mTOR inhibitors in patients being considered for transplantation remains a matter of debate, but the current consensus is that they should be used until transplantation is considered, and the patient should be thoroughly educated about the risks involved [ 63 - 65 ].…”