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Use of sirolimus in the treatment of lymphangioleiomyomatosis: favorable responses in patients with different extrapulmonary manifestations.

Freitas CS, Baldi BG, Araújo MS, Heiden GI, Kairalla RA, Carvalho CR - J Bras Pneumol (2015 May-Jun)

Bottom Line: The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day).After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement.However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

View Article: PubMed Central - PubMed

Affiliation: Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.

ABSTRACT

Objective: Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day).

Methods: We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus.

Results: After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma.

Conclusions: Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

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Related in: MedlinePlus

Chest X-rays taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing resolution of chylothorax.
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f01: Chest X-rays taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing resolution of chylothorax.

Mentions: A 48-year-old smoker (with a smoking history of 15 pack-years) was admitted with a two-year history of dyspnea, which had worsened one week prior. She reported no other diseases. The patient reported that she had undergone oophorectomy nine years prior because of a benign tumor and right nephrectomy six months prior because of renal angiomyolipoma. She had no relevant exposure history. Physical examination revealed that the patient had lost weight, breath sounds being absent in the right hemithorax and her SpO2 being 92% on room air. A chest X-ray showed a large right pleural effusion (Figure 1). The patient underwent thoracentesis, and a diagnosis of chylothorax was established. A pulmonary function test performed after chest tube drainage showed an FVC of 3.12 L (100% of predicted), an FEV1 of 1.95 L (75% of predicted), an FEV1/FVC ratio of 0.62, a TLC of 5.27 L (92% of predicted), and a DLCO of 15.41 mL/min/mmHg (65% of predicted; Table 1). A chest CT scan showed diffuse, well-defined lung cysts. Her dyspnea worsened, and she presented with difficult-to-manage chylothorax, with a high output from the chest tube despite treatment with total parenteral nutrition. A decision was made to treat her with sirolimus (at 1 mg/day). Resolution of the chylothorax and functional stability were observed after 12 months of treatment (Figure 1 and Table 1).


Use of sirolimus in the treatment of lymphangioleiomyomatosis: favorable responses in patients with different extrapulmonary manifestations.

Freitas CS, Baldi BG, Araújo MS, Heiden GI, Kairalla RA, Carvalho CR - J Bras Pneumol (2015 May-Jun)

Chest X-rays taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing resolution of chylothorax.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4541764&req=5

f01: Chest X-rays taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing resolution of chylothorax.
Mentions: A 48-year-old smoker (with a smoking history of 15 pack-years) was admitted with a two-year history of dyspnea, which had worsened one week prior. She reported no other diseases. The patient reported that she had undergone oophorectomy nine years prior because of a benign tumor and right nephrectomy six months prior because of renal angiomyolipoma. She had no relevant exposure history. Physical examination revealed that the patient had lost weight, breath sounds being absent in the right hemithorax and her SpO2 being 92% on room air. A chest X-ray showed a large right pleural effusion (Figure 1). The patient underwent thoracentesis, and a diagnosis of chylothorax was established. A pulmonary function test performed after chest tube drainage showed an FVC of 3.12 L (100% of predicted), an FEV1 of 1.95 L (75% of predicted), an FEV1/FVC ratio of 0.62, a TLC of 5.27 L (92% of predicted), and a DLCO of 15.41 mL/min/mmHg (65% of predicted; Table 1). A chest CT scan showed diffuse, well-defined lung cysts. Her dyspnea worsened, and she presented with difficult-to-manage chylothorax, with a high output from the chest tube despite treatment with total parenteral nutrition. A decision was made to treat her with sirolimus (at 1 mg/day). Resolution of the chylothorax and functional stability were observed after 12 months of treatment (Figure 1 and Table 1).

Bottom Line: The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day).After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement.However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

View Article: PubMed Central - PubMed

Affiliation: Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.

ABSTRACT

Objective: Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day).

Methods: We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus.

Results: After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma.

Conclusions: Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

Show MeSH
Related in: MedlinePlus