LIGHT CHAIN AMYLOIDOSIS
Light chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic lights chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment...
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PAGEPress Publications
2018-03-01
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Series: | Mediterranean Journal of Hematology and Infectious Diseases |
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doaj-bca67fd478654adfa2f42114f52f93792020-11-24T23:07:50ZengPAGEPress PublicationsMediterranean Journal of Hematology and Infectious Diseases2035-30062018-03-01101e2018022e201802210.4084/mjhid.2018.0221746LIGHT CHAIN AMYLOIDOSISPaolo Milani0Giampaolo Merlini1Giovanni Palladini2Amyloidosis Research and Treatment Center, Foundation “Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo” and Department of Molecular Medicine, University of Pavia, Pavia, ItalyAmyloidosis Research and Treatment Center, Foundation “Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo” and Department of Molecular Medicine, University of Pavia, Pavia, ItalyAmyloidosis Research and Treatment Center, Foundation “Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo” and Department of Molecular Medicine, University of Pavia, Pavia, ItalyLight chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic lights chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by response to therapy. The specific treatment is chemotherapy targeting the underlying plasma-cell clone. This needs be risk adapted, according to the severity of cardiac and/or multi-organ involvement. Autologous stem cell transplant (preceded by induction and/or followed by consolidation with bortezomib-based regimens) can be considered for low-risk patients (~20%). Bortezomib combined with alkylators is used in the majority of intermediate-risk patients, and with possible dose escalation in high-risk subjects. Novel, powerful anti-plasma cell agents were investigated in the relapsed/refractory setting, and are being moved to upfront therapy in clinical trials. In addition, the use of novel approaches based on antibodies targeting the amyloid deposits or small molecules interfering with the amyloidogenic process gave promising results in preliminary studies. Some of them are under evaluation in controlled trials. These molecules will probably add powerful complements to standard chemotherapy. The understanding of the specific molecular mechanisms of cardiac damage and the characteristics of the amyloidogenic clone are unveiling novel potential treatment approaches, moving towards a cure for this dreadful disease.https://www.mjhid.org/index.php/mjhid/article/view/3292 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Paolo Milani Giampaolo Merlini Giovanni Palladini |
spellingShingle |
Paolo Milani Giampaolo Merlini Giovanni Palladini LIGHT CHAIN AMYLOIDOSIS Mediterranean Journal of Hematology and Infectious Diseases |
author_facet |
Paolo Milani Giampaolo Merlini Giovanni Palladini |
author_sort |
Paolo Milani |
title |
LIGHT CHAIN AMYLOIDOSIS |
title_short |
LIGHT CHAIN AMYLOIDOSIS |
title_full |
LIGHT CHAIN AMYLOIDOSIS |
title_fullStr |
LIGHT CHAIN AMYLOIDOSIS |
title_full_unstemmed |
LIGHT CHAIN AMYLOIDOSIS |
title_sort |
light chain amyloidosis |
publisher |
PAGEPress Publications |
series |
Mediterranean Journal of Hematology and Infectious Diseases |
issn |
2035-3006 |
publishDate |
2018-03-01 |
description |
Light chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic lights chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by response to therapy. The specific treatment is chemotherapy targeting the underlying plasma-cell clone. This needs be risk adapted, according to the severity of cardiac and/or multi-organ involvement. Autologous stem cell transplant (preceded by induction and/or followed by consolidation with bortezomib-based regimens) can be considered for low-risk patients (~20%). Bortezomib combined with alkylators is used in the majority of intermediate-risk patients, and with possible dose escalation in high-risk subjects. Novel, powerful anti-plasma cell agents were investigated in the relapsed/refractory setting, and are being moved to upfront therapy in clinical trials. In addition, the use of novel approaches based on antibodies targeting the amyloid deposits or small molecules interfering with the amyloidogenic process gave promising results in preliminary studies. Some of them are under evaluation in controlled trials. These molecules will probably add powerful complements to standard chemotherapy. The understanding of the specific molecular mechanisms of cardiac damage and the characteristics of the amyloidogenic clone are unveiling novel potential treatment approaches, moving towards a cure for this dreadful disease. |
url |
https://www.mjhid.org/index.php/mjhid/article/view/3292 |
work_keys_str_mv |
AT paolomilani lightchainamyloidosis AT giampaolomerlini lightchainamyloidosis AT giovannipalladini lightchainamyloidosis |
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