- •Lymphangioleiomyomatosis is a rare indication for lung transplantation.
- •Use of mTOR inhibitors in LAM patients on the waiting list is controversial.
- •Our survey results suggest excellent outcomes in patients using mTOR inhibitor while on the waitlist.
- •Guidelines regarding use of mTOR inhibitors in LAM patients on the waitlist should be reconsidered.
Lymphangioleiomyomatosis (LAM) is an uncommon indication for lung transplantation. The use of mechanistic target of rapamycin (mTOR) inhibitors, which are the mainstay of treatment in progressive LAM, in patients awaiting lung transplant is controversial. We sought to examine worldwide practice patterns in use of mTOR inhibitors in LAM patients on the lung transplant waiting list.
We designed and disseminated an online survey about institution-specific practice patterns, particularly regarding listing LAM patients for lung transplant and use of mTOR inhibitors in those patients on the transplant waitlist.
Of the 49 unique respondent programs, 83.6% had previously listed a LAM patient for lung transplant. Thirteen centers allowed patients to continue on mTOR inhibitor until time of lung transplant. None of those centers reported any complications or deaths attributable to mTOR inhibitor adverse effects.
There exists significant variability in practice patterns concerning the use of mTOR inhibitors in LAM patients on the lung transplant waiting list. Our survey suggests favorable outcomes for those patients that did continue mTOR inhibitor up to time of transplant. Further data regarding the risk of anastomotic complication with use of mTOR inhibitors in the pre-transplant period would help provide clarity in this debate.
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- Lymphangioleiomyomatosis: clinical features, management and basic mechanisms.Thorax. 1999; 54: 254-264
- Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex.Am. J. Respir. Crit. Care Med. 2001; 164: 669-671
- Pulmonary lymphangioleiomyomatosis. A study of 69 patients. Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P).Medicine (Baltim.). 1999; 78: 321-337
- High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex.Mayo Clin. Proc. 2000; 75: 591-594
- Pulmonary lymphangioleiomyomatosis in a man.Am. J. Respir. Crit. Care Med. 2000; 162: 749-752
- Pulmonary lymphangioleiomyomatosis in a karyotypically normal man without tuberous sclerosis complex.Am. J. Respir. Crit. Care Med. 2007; 176: 96-98
- Decline in lung function in patients with lymphangioleiomyomatosis treated with or without progesterone.Chest. 2004; 126: 1867-1874
- The international thoracic organ transplant registry of the international society for heart and lung transplantation: thirty-sixth adult lung and heart-lung transplantation report-2019; focus theme: donor and recipient size match.J. Heart Lung Transplant. 2019; 38: 1042-1055
- Pulmonary lymphangiomyomatosis. A review.Am. J. Pathol. 1975; 79: 348-382
- Lymphangioleiomyomatosis. Physiologic-pathologic-radiologic correlations.Am. Rev. Respir. Dis. 1977; 116: 977-995
- Lymphangioleiomyomatosis (LAM): a review of clinical and morphological features.J. Nippon Med. Sch. 2000; 67: 311-329
- Clinical utility of diagnostic guidelines and putative biomarkers in lymphangioleiomyomatosis.Respir. Res. 2012; 13: 34
- Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis.Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 17462-17467
- Lymphangioleiomyomatosis.Clin. Chest Med. 2016; 37: 389-403
- Integration of mTOR and estrogen-ERK2 signaling in lymphangioleiomyomatosis pathogenesis.Proc. Natl. Acad. Sci. U.S.A. 2013; 110: 14960-14965
- Downregulation of estrogen and progesterone receptors in the abnormal smooth muscle cells in pulmonary lymphangioleiomyomatosis following therapy. An immunohistochemical study.Am. J. Respir. Crit. Care Med. 2000; 161: 1002-1009
- Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis.Proc. Natl. Acad. Sci. U.S.A. 2000; 97: 6085-6090
- Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis.N. Engl. J. Med. 2008; 358: 200-203
- Efficacy and safety of sirolimus in lymphangioleiomyomatosis.N. Engl. J. Med. 2011; 364: 1595-1606
- Everolimus for the treatment of lymphangioleiomyomatosis: a phase II study.Eur. Respir. J. 2015; 46: 783-794
- Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial.Lancet. 2013; 381: 817-824
- Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis.N. Engl. J. Med. 2008; 358: 140-151
- Dose-level response rates of mTor inhibition in tuberous sclerosis complex (TSC) related subependymal giant cell astrocytoma (SEGA).Pediatr. Blood Cancer. 2015; 62: 1754-1760
- Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial.Lancet. 2013; 381: 125-132
- Official American thoracic society/Japanese respiratory society clinical practice guidelines: lymphangioleiomyomatosis diagnosis and management.Am. J. Respir. Crit. Care Med. 2016; 194: 748-761
- Organ procurement and transplantation Network website.September 16, 2020https://optn.transplant.hrsa.gov/data/Date accessed: January 3, 2022
- Combined heart-and-lung transplantation for lymphangioleiomyomatosis.Lancet. 1984; 1: 275
- The US experience with lung transplantation for pulmonary lymphangioleiomyomatosis.J. Heart Lung Transplant. 2005; 24: 1247-1253
- Clinical outcomes and survival following lung transplantation in patients with lymphangioleiomyomatosis.J. Heart Lung Transplant. 2019; 38: 949-955
- Development of the new lung allocation system in the United States.Am. J. Transplant. 2006; 6: 1212-1227
- Airway anastomotic dehiscence associated with use of sirolimus immediately after lung transplantation.Transplantation. 2003; 75: 1437-1443
- Airway anastomosis complications in de novo lung transplantation with sirolimus-based immunosuppression.J. Heart Lung Transplant. 2004; 23: 632-638
- European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis.Eur. Respir. J. 2010; 35: 14-26
- An investigator-driven study of everolimus in surgical lung biopsy confirmed idiopathic pulmonary fibrosis.Respirology. 2011; 16: 776-783
- Should mammalian target of rapamycin inhibitors be stopped in women with lymphangioleiomyomatosis awaiting lung transplantation?.Expet Rev. Respir. Med. 2014; 8: 657-660
- United States Food and drug Administration.July 2011https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021083s059,021110s076lbl.pdfDate accessed: February 15, 2021
- A retrospective study of lung transplantation in patients with lymphangioleiomyomatosis: challenges and outcomes.Front. Med. 2021; 8: 584826
- Experience of lung transplantation in patients with lymphangioleiomyomatosis at a Brazilian reference centre.Lung. 2017; 195: 699-705
- Favorable survival even with high disease-specific complication rates in lymphangioleiomyomatosis after lung transplantation-long-term follow-up of a Japanese center.Clin. Res. J. 2020; 14: 116-123
- Three-year results of an investigator-driven multicenter, international, randomized open-label de novo trial to prevent BOS after lung transplantation.J. Heart Lung Transplant. 2015; 34: 16-25
- Effects of prophylactic use of sirolimus on bronchiolitis obliterans syndrome development in lung transplant recipients.Ann. Thorac. Surg. 2014; 97: 268-274
Published online: March 04, 2022
Accepted: February 17, 2022
Received in revised form: January 6, 2022
Received: November 9, 2021
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