RESUMO
Background: Pediatric acute myeloid leukemia (AML) therapy is associated with substantial short- and long-term treatment-related cardiotoxicity mainly due to high-dose anthracycline exposure. Early left ventricular systolic dysfunction (LVSD) compromises anthracycline delivery and is associated with inferior event-free and overall survival in de novo pediatric AML. Thus, effective cardioprotective strategies and cardiotoxicity risk predictors are critical to optimize cancer therapy delivery and enable early interventions to prevent progressive LVSD. While dexrazoxane-based cardioprotection reduces short-term cardiotoxicity without compromising cancer survival, liposomal anthracycline formulations have the potential to mitigate cardiotoxicity while improving antitumor efficacy. This overview summarizes the rationale and methodology of cardiac substudies within AAML1831, a randomized Children's Oncology Group Phase 3 study of CPX-351, a liposomal formulation of daunorubicin and cytarabine, in comparison with standard daunorubicin/cytarabine with dexrazoxane in the treatment of de novo pediatric AML. Methods/design: Children (age <22 years) with newly diagnosed AML were enrolled and randomized to CPX-351-containing induction 1 and 2 (Arm A) or standard daunorubicin and dexrazoxane-containing induction (Arm B). Embedded cardiac correlative studies aim to compare the efficacy of this liposomal anthracycline formulation to dexrazoxane for primary prevention of cardiotoxicity by detailed core lab analysis of standardized echocardiograms and serial cardiac biomarkers throughout AML therapy and in follow-up. In addition, AAML1831 will assess the ability of early changes in sensitive echo indices (e.g., global longitudinal strain) and cardiac biomarkers (e.g., troponin and natriuretic peptides) to predict subsequent LVSD. Finally, AAML1831 establishes expert consensus-based strategies in cardiac monitoring and anthracycline dose modification to balance the potentially competing priorities of cardiotoxicity reduction with optimal leukemia therapy. Discussion: This study will inform diagnostic, prognostic, preventative, and treatment strategies regarding cardiotoxicity during pediatric AML therapy. Together, these measures have the potential to improve leukemia-free and overall survival and long-term cardiovascular health in children with AML. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04293562.
RESUMO
BACKGROUND: Systematic characterization of heart failure in adults in Ethiopia is lacking currently. In this review, we sought to summarize the available scientific evidence on the epidemiology, treatment and prognosis of heart failure in adults in Ethiopia. METHODS: A systematic review of PUBMED, EMBASE and SCOPUS was conducted for studies published between January 1990 and July 2017. Studies reporting on incidence, prevalence, treatment or prognosis of heart failure in individuals older than 14 years of age were included. RESULTS: The search yielded 66 articles, out of which nine were found to be eligible for inclusion in this review. There are no studies reporting the incidence or prevalence of heart failure in the adult population in Ethiopia. There are, however, indications that heart failure might be a significant burden in the country, and typically affects middle-aged adults. Valvular heart disease, predominantly related to rheumatic heart disease, is the most commonly identified heart failure cause across the included studies. There are very limited data on treatment and prognosis. CONCLUSION: There is limited scientific evidence on the epidemiology, treatment and prognosis of heart failure in adults in Ethiopia. Further studies are needed for the better understanding of the burden and treatment of heart failure in the adult population in Ethiopia.
