Sirolimus Ameliorated Post Lung Transplant Chylothorax in Lymphangioleiomyomatosis

doi:10.1016/j.athoracsur.2008.07.062

The Annals of Thoracic Surgery

Volume 86, Issue 6, December 2008, Pages e7-e8

https://doi.org/10.1016/j.athoracsur.2008.07.062 Get rights and content

We report a successful case of sirolimus treatment for chylous pleural and peritoneal effusions of lymphangioleiomyomatosis after lung transplantation. A 32-year-old woman underwent living donor lung transplantation. Persistent chylous pleural and peritoneal effusions were seen postoperatively. Pleurodesis by intrathoracic injection of OK-432, minomycin, and somatostatine analog failed to control chylous effusions. However, sirolimus treatment reduced the amount of chylous drainage and improved both chylous pleural and peritoneal effusions.

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Lymphangioleiomyomatosis is a rare disease associated with loss of function of the tumor suppressor gene tuberous sclerosis (TSC)1 and TSC2, resulting in constitutive activation of the mammalian target of rapamycin [6, 7]. Loss of TSC2 GTPase Activating Protein activity or disruption of the TSC1/TSC2 complex deregulates ribosomal protein S6 kinase 1 activation, which leads to abnormal cell proliferation [6].

Recently, sirolimus, a specific S6 kinase 1 inhibitor that blocks growth factor-driven

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Cited by (38)

Common Noninfectious Complications Following Lung Transplantation
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Recommendations of the Spanish Society of Cardiorespiratory Rehabilitation on lung transplantation
2016, Rehabilitacion
Desde que se realizó el primer trasplante pulmonar en 1963, el procedimiento se ha extendido gradualmente. Tras la primera intervención con éxito en 1983, la técnica ha evolucionado y se ha perfeccionado, consiguiéndose un incremento de la supervivencia en los pacientes trasplantados. A este incremento en la supervivencia contribuye indudablemente la correcta evaluación, selección y preparación de candidatos a trasplante pulmonar realizada desde la Medicina Física y Rehabilitación. Actualmente la evaluación y optimización funcional pre y postrasplante aportada desde esta especialidad es clave en el éxito del trasplante pulmonar. Dada la importancia de este hecho, se nombró un grupo de expertos por la Sociedad Española de Rehabilitación Cardio-Respiratoria (SORECAR) para realizar una revisión de la evidencia actual al respecto y redactar un documento consenso de actuación en el trasplante pulmonar.
Since the first lung transplant was carried out in 1963, this procedure has gradually spread. After the first successful lung transplant in 1983, the technique has evolved and has been perfected, leading to an increase in survival among transplant recipients. Factors that have undoubtedly contributed to this increased survival are thorough evaluation, selection and preparation of lung transplant candidates by specialists in physical medicine and rehabilitation. At present, the assessment and functional optimization both pre- and post-transplant provided by this specialty are crucial to lung transplant success. A group of experts was therefore appointed by the Spanish Society of Cardiorespiratory Rehabilitation to review the current evidence on this topic and to produce a consensus document on interventions in lung transplantation.
Therapeutic effect of sirolimus for lymphangioleiomyomatosis remaining in the abdominopelvic region after lung transplantation: A case report
2016, Transplantation Proceedings
Sirolimus (SRL) is used to treat pulmonary lymphangioleiomyomatosis (P-LAM). There is limited evidence that SRL has systemic efficacy for the patients with extrapulmonary lymphangioleiomyomatosis (E-LAM) remaining after lung transplantation (LT) for P-LAM. This report examines the efficacy of SRL treatment for the patient with E-LAM remaining after an LT for P-LAM.
The course of the patient's recovery from an LT for P-LAM was complicated by lymphedema in the left femoral region that was caused by two E-LAM lesions remaining in the left pelvic cavity and in the retroperitoneal area. After the LT was performed, the patient started SRL treatment to reduce the E-LAM lesions. The daily SRL dose, selected based on the standard SRL dose for P-LAM, was initiated at 1 mg/d and was maintained at 2 mg/d. The remaining E-LAM lesions and lymphedema in the left femoral region improved in approximately 9 months after the LT with the administration of both SRL and the standard immunosuppressive therapy used by Okayama University Hospital, including tacrolimus, mycophenolate mofetil, and prednisolone. The SRL and tacrolimus trough concentrations in whole blood were maintained within the therapeutic window for the next 1.5 years after initiation of SRL treatment. The patient experienced no severe adverse events that required discontinuation of the SRL treatment during this time.
The patients with remaining E-LAM lesions may receive SRL treatment to improve the quality of life after LT for P-LAM as effective therapy in cases where the patient's recovery is complicated by E-LAM lesions.
The efficacy and safety of low-dose sirolimus for treatment of lymphangioleiomyomatosis
2013, Respiratory Investigation
Citation Excerpt :
In that trial, sirolimus was administered to maintain blood trough level of 5–15 ng/mL, which was chosen on the basis of results of the CAST. However, it remains unclear whether this is the optimal level for the treatment of LAM, especially as other recent case reports have shown that a lower dose was also effective [12,13]. Therefore, to determine the efficacy and safety of sirolimus at a concentration lower than the currently recommended trough level, we conducted an observational study of Japanese patients with LAM who took sirolimus at doses that maintained blood trough levels lower than the currently recommended target of 5–15 ng/mL.
Lymphangioleiomyomatosis (LAM) is a rare disease caused by dysregulated activation of the mammalian target of rapamycin (mTOR). Sirolimus, an inhibitor of mTOR, has been reported to decrease the size of angiomyolipomas and stabilize pulmonary function in patients with LAM. However, the optimal dose for the treatment of LAM remains unclear.
We conducted a retrospective, observational study of 15 patients with LAM who underwent sirolimus therapy for more than 6 months. The efficacy was evaluated by reviewing the patients' clinical courses, pulmonary function and chest radiologic findings before and after the initiation of sirolimus treatment.
All patients had blood trough levels of sirolimus lower than 5 ng/mL. Sirolimus treatment improved the annual rates of change in FVC and FEV₁ in the 9 patients who were free from chylous effusion (FVC, −101.0 vs. +190.0 mL/y, p=0.046 and FEV₁, −115.4 vs. +127.8 mL/y, p=0.015). The remaining 7 patients had chylous effusion at the start of sirolimus treatment; the chylothorax resolved completely within 1−5 months of treatment in 6 of these cases. These results resembled those of previous studies in which blood trough levels of sirolimus ranged from 5 to 15 ng/mL.
Low-dose sirolimus (trough level, 5 ng/mL or less) performed as well as the higher doses used previously for improving pulmonary function and decreasing chylous effusion in patients with LAM.
Peritoneovenous shunt for chylous ascites after lung transplantation for lymphangioleiomyomatosis
2012, Transplantation Proceedings
Citation Excerpt :
However, frequent paracenteses should be avoided after lung transplantation due to the risk of infection. Several studies suggest that sirolimus treatment can reduce chylous ascites.5,6 However, the accumulation of ascitic fluid was refractory to sirolimus in our patient.
A 37-year-old woman with lymphangioleiomyomatosis (LAM) who underwent right single-lung transplantation from a cadaveric donor developed persistent chylous ascites. Despite use of diuretics and sirolimus to reduce ascites-associated symptoms and to prevent gastroesophageal reflex triggered by increased abdominal pressure, the ascites were refractory, and periodic paracenteses were required. With placement of a peritoneovenous shunt (Denver shunt), the patient's abdominal circumference decreased, and her symptoms abated. Thus, placement of a peritoneovenous shunt can be an effective management strategy for refractory chylous ascites in patients with LAM, even after lung transplantation.
Progress in the treatment of lymphangioleiomyomatosis: From bench to bedside
2012, Revista Portuguesa de Pneumologia (English Edition)

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Case reportSirolimus Ameliorated Post Lung Transplant Chylothorax in Lymphangioleiomyomatosis

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Chest

Chest

Chest

Curr Opin Genet Dev

J Heart Lung Transplant

Case report
Sirolimus Ameliorated Post Lung Transplant Chylothorax in Lymphangioleiomyomatosis