Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement.
<h4>Background</h4>Cardiac light chain amyloidosis (AL-CA) patients often die within three months of starting chemotherapy. Chemotherapy for non-immunoglobulin M gammopathy with AL-CA frequently includes bortezomib (Bor), cyclophosphamide (Cy), and dexamethasone (D). We previously report...
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oai:doaj.org-article:bbbf2a9e4d304b4583602af0c7c9d90b2021-12-02T20:06:16ZDexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement.1932-620310.1371/journal.pone.0257189https://doaj.org/article/bbbf2a9e4d304b4583602af0c7c9d90b2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257189https://doaj.org/toc/1932-6203<h4>Background</h4>Cardiac light chain amyloidosis (AL-CA) patients often die within three months of starting chemotherapy. Chemotherapy for non-immunoglobulin M gammopathy with AL-CA frequently includes bortezomib (Bor), cyclophosphamide (Cy), and dexamethasone (D). We previously reported that NT-ProBNP levels can double within 24h of dexamethasone administration, suggesting a deleterious impact on cardiac function. In this study, we evaluate the role of dexamethasone in early cardiovascular mortality during treatment.<h4>Methods and findings</h4>We retrospectively assessed 100 de novo cardiac AL patients (62% male, mean age 68 years) treated at our institute between 2009 and 2018 following three chemotherapy regimens: CyBorDComb (all initiated on day 1; 34 patients), DCyBorSeq (D, day 1; Cy, day 8; Bor, day 15; 17 patients), and CyBorDSeq (Cy, day 1; Bor, day 8; D, day 15; 49 patients). The primary endpoint was cardiovascular mortality and cardiac transplantation at days 22 and 455. At day 22, mortality was 20.6% with CyBorDComb, 23.5% with DCyBorSeq, and 0% with CyBorDSeq (p = 0.003). At day 455, mortality was not significantly different between regimens (p = 0.195). Acute toxicity of dexamethasone was evaluated on myocardial function using a rat model of isolated perfused heart. Administration of dexamethasone induced a decrease in left ventricular myocardium contractility and relaxation (p<0.05), supporting a potential negative inotropic effect of dexamethasone in AL-CA patients with severe cardiac involvement.<h4>Conclusion</h4>Delaying dexamethasone during the first chemotherapy cycle reduces the number of early deaths without extending survival. It is clear that dexamethasone is beneficial in the long-term treatment of patients with AL-CA. However, the initial introduction of dexamethasone during treatment is critical, but may be associated with early cardiac deaths in severe CA. Thus, it is important to consider the dosage and timing of dexamethasone introduction on a patient-severity basis. The impact of dexamethasone in the treatment of AL-CA needs further investigation.Mélanie BézardSilvia OghinaDamien VitielloMounira KharoubiEkaterini KordeliArnault GalatAmira ZarouiSoulef GuendouzFloriane GillesJason ShourickDavid HamonVincent AudardEmmanuel TeigerElsa PoullotValérie Molinier-FrenkelFrançois LemonnierOnnik AgbulutFabien Le BrasThibaud DamyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257189 (2021) |
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Medicine R Science Q Mélanie Bézard Silvia Oghina Damien Vitiello Mounira Kharoubi Ekaterini Kordeli Arnault Galat Amira Zaroui Soulef Guendouz Floriane Gilles Jason Shourick David Hamon Vincent Audard Emmanuel Teiger Elsa Poullot Valérie Molinier-Frenkel François Lemonnier Onnik Agbulut Fabien Le Bras Thibaud Damy Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement. |
| description |
<h4>Background</h4>Cardiac light chain amyloidosis (AL-CA) patients often die within three months of starting chemotherapy. Chemotherapy for non-immunoglobulin M gammopathy with AL-CA frequently includes bortezomib (Bor), cyclophosphamide (Cy), and dexamethasone (D). We previously reported that NT-ProBNP levels can double within 24h of dexamethasone administration, suggesting a deleterious impact on cardiac function. In this study, we evaluate the role of dexamethasone in early cardiovascular mortality during treatment.<h4>Methods and findings</h4>We retrospectively assessed 100 de novo cardiac AL patients (62% male, mean age 68 years) treated at our institute between 2009 and 2018 following three chemotherapy regimens: CyBorDComb (all initiated on day 1; 34 patients), DCyBorSeq (D, day 1; Cy, day 8; Bor, day 15; 17 patients), and CyBorDSeq (Cy, day 1; Bor, day 8; D, day 15; 49 patients). The primary endpoint was cardiovascular mortality and cardiac transplantation at days 22 and 455. At day 22, mortality was 20.6% with CyBorDComb, 23.5% with DCyBorSeq, and 0% with CyBorDSeq (p = 0.003). At day 455, mortality was not significantly different between regimens (p = 0.195). Acute toxicity of dexamethasone was evaluated on myocardial function using a rat model of isolated perfused heart. Administration of dexamethasone induced a decrease in left ventricular myocardium contractility and relaxation (p<0.05), supporting a potential negative inotropic effect of dexamethasone in AL-CA patients with severe cardiac involvement.<h4>Conclusion</h4>Delaying dexamethasone during the first chemotherapy cycle reduces the number of early deaths without extending survival. It is clear that dexamethasone is beneficial in the long-term treatment of patients with AL-CA. However, the initial introduction of dexamethasone during treatment is critical, but may be associated with early cardiac deaths in severe CA. Thus, it is important to consider the dosage and timing of dexamethasone introduction on a patient-severity basis. The impact of dexamethasone in the treatment of AL-CA needs further investigation. |
| format |
article |
| author |
Mélanie Bézard Silvia Oghina Damien Vitiello Mounira Kharoubi Ekaterini Kordeli Arnault Galat Amira Zaroui Soulef Guendouz Floriane Gilles Jason Shourick David Hamon Vincent Audard Emmanuel Teiger Elsa Poullot Valérie Molinier-Frenkel François Lemonnier Onnik Agbulut Fabien Le Bras Thibaud Damy |
| author_facet |
Mélanie Bézard Silvia Oghina Damien Vitiello Mounira Kharoubi Ekaterini Kordeli Arnault Galat Amira Zaroui Soulef Guendouz Floriane Gilles Jason Shourick David Hamon Vincent Audard Emmanuel Teiger Elsa Poullot Valérie Molinier-Frenkel François Lemonnier Onnik Agbulut Fabien Le Bras Thibaud Damy |
| author_sort |
Mélanie Bézard |
| title |
Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement. |
| title_short |
Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement. |
| title_full |
Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement. |
| title_fullStr |
Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement. |
| title_full_unstemmed |
Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement. |
| title_sort |
dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/bbbf2a9e4d304b4583602af0c7c9d90b |
| work_keys_str_mv |
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