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Case Reports
. 2015 May-Jun;41(3):275-80.
doi: 10.1590/S1806-37132015000004553.

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

[Article in English, Portuguese]
Carolina Salim Gonçalves Freitas  1 , Bruno Guedes Baldi  1 , Mariana Sponholz Araújo  1 , Glaucia Itamaro Heiden  1 , Ronaldo Adib Kairalla  1 , Carlos Roberto Ribeiro Carvalho  1
Affiliations
Case Reports

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

[Article in English, Portuguese]
Carolina Salim Gonçalves Freitas et al. J Bras Pneumol. 2015 May-Jun.

Abstract
in English, Portuguese

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.

OBJETIVO:: A linfangioleiomiomatose (LAM) é uma doença rara que é atualmente considerada uma neoplasia de baixo grau com potencial metastático e evolução variável. Os inibidores de mammalian target of rapamycin (mTOR), como o sirolimo e o everolimo, recentemente se tornaram uma opção para o tratamento de pacientes com LAM, especialmente daqueles com manifestações extrapulmonares. O objetivo deste estudo foi descrever quatro casos de pacientes com LAM no Brasil que apresentaram melhora, especialmente das manifestações extrapulmonares, após tratamento com sirolimo (em doses de 1-4 mg/dia).

MÉTODOS:: Descrevemos quatro casos de pacientes com LAM e diferentes manifestações extrapulmonares tratados com sirolimo.

RESULTADOS:: Após o tratamento com sirolimo por 12 meses, um paciente apresentou resolução do quilotórax de difícil manejo, um paciente teve redução significativa do volume do angiomiolipoma renal, e uma paciente apresentou regressão importante de linfangioleiomiomas retroperitoneais e linfonodomegalias abdominais. Após tratamento com sirolimo por 6 meses, um paciente apresentou redução significativa de volumoso linfangioleiomioma retroperitoneal.

CONCLUSÕES:: Nossos achados confirmam que os inibidores de mTOR são benéficos para pacientes com LAM, especialmente para aqueles com manifestações extrapulmonares, tais como angiomiolipomas renais, linfangioleiomiomas e derrames de origem quilosa. Entretanto, alguns pontos, tais como a dose ideal, a duração do tratamento e os efeitos adversos em longo prazo, ainda precisam ser esclarecidos para que os inibidores de mTOR possam ser incorporados na abordagem da LAM.

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Figures

Figure 1.
Figure 1.. 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.
Figure 2.
Figure 2.. Abdominal CT scans taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing a reduction in bilateral renal angiomyolipoma volume.
Figure 3.
Figure 3.. Abdominal CT scans taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing a significant reduction in retroperitoneal lymphangioleiomyoma volume (white arrow).
Figure 4.
Figure 4.. Abdominal CT scans taken before treatment with sirolimus (in A) and after 6 months of treatment with the drug (in B), showing resolution of an abdominal lymphangioleiomyoma (white arrow).
Figura 1.
Figura 1.. Radiografia de tórax antes do tratamento com sirolimo (em A) e após 12 meses de tratamento com o medicamento (em B), mostrando a resolução do quilotórax.
Figura 2.
Figura 2.. TC de abdome antes do tratamento com sirolimo (em A) e após 12 meses de tratamento com o medicamento (em B), mostrando diminuição do volume dos angiomiolipomas renais bilaterais.
Figura 3.
Figura 3.. TC de abdome antes do tratamento com sirolimo (em A) e após 12 meses de tratamento com o medicamento (em B), mostrando diminuição importante do volume dos linfangioleiomiomas retroperitoneais (seta branca).
Figura 4.
Figura 4.. TC de abdome antes do tratamento com sirolimo (em A) e após 6 meses de tratamento com o medicamento (em B), mostrando resolução de linfangioleiomioma abdominal (seta branca).
See this image and copyright information in PMC

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