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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

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).
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f07: 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).

Mentions: Uma paciente de 26 anos, não tabagista, com dispneia aos esforços havia três anos, apresentou piora aguda do quadro. Em 2011, foi identificado quilotórax volumoso, que não foi investigado na época. Após um ano, a paciente foi internada para investigação. As TCs de tórax e de abdome evidenciaram cistos difusos no parênquima pulmonar, além de volumosos linfangioleiomiomas retroperitoneais e linfonodomegalias abdominais. Confirmou-se o diagnóstico de LAM, e a prova de função pulmonar inicial apresentou os seguintes resultados: CVF de 2,36 l (61% do previsto), VEF1 de 1,49 l (46% do previsto) e VEF1/CVF de 0,63. Foi iniciado o tratamento com sirolimo (2 mg/dia) e, após 12 meses de tratamento, a paciente apresentou regressão significativa das massas retroperitoneais e abdominais (Figura 3), além de melhora da função pulmonar (Tabela 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)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f07: 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).
Mentions: Uma paciente de 26 anos, não tabagista, com dispneia aos esforços havia três anos, apresentou piora aguda do quadro. Em 2011, foi identificado quilotórax volumoso, que não foi investigado na época. Após um ano, a paciente foi internada para investigação. As TCs de tórax e de abdome evidenciaram cistos difusos no parênquima pulmonar, além de volumosos linfangioleiomiomas retroperitoneais e linfonodomegalias abdominais. Confirmou-se o diagnóstico de LAM, e a prova de função pulmonar inicial apresentou os seguintes resultados: CVF de 2,36 l (61% do previsto), VEF1 de 1,49 l (46% do previsto) e VEF1/CVF de 0,63. Foi iniciado o tratamento com sirolimo (2 mg/dia) e, após 12 meses de tratamento, a paciente apresentou regressão significativa das massas retroperitoneais e abdominais (Figura 3), além de melhora da função pulmonar (Tabela 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