失调
肠道菌群
免疫学
殖民抵抗
生物
阿糖胞苷
柔红霉素
移植
免疫系统
髓样
造血干细胞移植
白血病
医学
微生物学
抗生素
内科学
作者
Giorgia Renga,Emilia Nunzi,Claudia Stincardini,Marilena Pariano,Matteo Puccetti,Giuseppe Pieraccini,Claudia Di Serio,Maurizio Fraziano,Noemi Poerio,Vasileios Oikonomou,Paolo Mosci,Enrico Garaci,Luana Fianchi,Livio Pagano,Luigina Romani
出处
期刊:Blood
[American Society of Hematology]
日期:2024-01-16
卷期号:143 (16): 1628-1645
被引量:3
标识
DOI:10.1182/blood.2023021380
摘要
Abstract CPX-351, a liposomal combination of cytarabine plus daunorubicin, has been approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes, because it improves survival and outcome of patients who received hematopoietic stem cell transplant compared with the continuous infusion of cytarabine plus daunorubicin (referred to as “7 + 3” combination). Because gut dysbiosis occurring in patients with AML during induction chemotherapy heavily affects the subsequent phases of therapy, we have assessed whether the superior activity of CPX-351 vs “7 + 3” combination in the real-life setting implicates an action on and by the intestinal microbiota. To this purpose, we have evaluated the impact of CPX-351 and “7 + 3” combination on mucosal barrier function, gut microbial composition and function, and antifungal colonization resistance in preclinical models of intestinal damage in vitro and in vivo and fecal microbiota transplantation. We found that CPX-351, at variance with “7 + 3” combination, protected from gut dysbiosis, mucosal damage, and gut morbidity while increasing antifungal resistance. Mechanistically, the protective effect of CPX-351 occurred through pathways involving both the host and the intestinal microbiota, namely via the activation of the aryl hydrocarbon receptor–interleukin-22 (IL-22)–IL-10 host pathway and the production of immunomodulatory metabolites by anaerobes. This study reveals how the gut microbiota may contribute to the good safety profile, with a low infection-related mortality, of CPX-351 and highlights how a better understanding of the host-microbiota dialogue may contribute to pave the way for precision medicine in AML.
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