Purpose This retrospective cohort study aimed to determine the predictive relevance of clinical characteristics, additional cytogenetic aberrations, and cKIT and RAS mutations, as well as to evaluate whether specific treatment elements were associated with outcomes in pediatric t(8;21)-positive patients with acute myeloid leukemia (AML). Patients and Methods Karyotypes of 916 pediatric patients with t(8;21)-AML were reviewed for the presence of additional cytogenetic aberrations, and 228 samples were screened for presence of cKIT and RAS mutations. Multivariable regression models were used to assess the relevance of anthracyclines, cytarabine, and etoposide during induction and overall treatment. End points were the probability of achieving complete remission, cumulative incidence of relapse (CIR), probability of event-free survival, and probability of overall survival. Results Of 838 patients included in final analyses, 92% achieved complete remission. The 5-year overall survival, event-free survival, and CIR were 74%, 58%, and 26%, respectively. cKIT mutations and RAS mutations were not significantly associated with outcome. Patients with deletions of chromosome arm 9q [del(9q); n = 104] had a lower probability of complete remission (P = .01). Gain of chromosome 4 (+4; n = 21) was associated with inferior CIR and survival (P < .01). Anthracycline doses greater than 150 mg/m2 and etoposide doses greater than 500 mg/m2 in the first induction course and high-dose cytarabine 3 g/m2 during induction were associated with better outcomes on various end points. Cumulative doses of cytarabine greater than 30 g/m2 and etoposide greater than 1,500 mg/m2 were associated with lower CIR rates and better probability of event-free survival. Conclusion Pediatric patients with t(8;21)-AML and additional del(9q) or additional +4 might not be considered at good risk. Patients with t(8;21)-AML likely benefit from protocols that have high doses of anthracyclines, etoposide, and cytarabine during induction, as well as from protocols comprising cumulative high doses of cytarabine and etoposide.
The growing use of silver nanoparticles (Ag-NP) triggered an increasing interest in their environmental fate and possible ecotoxicological impacts. To investigate the potential risk of Ag-NP to soil organisms, the springtail Folsomia candida was exposed to Ag-NP (reported diameter size 3-8 nm) and AgNO3 in Lufa 2.2 natural soil for 28 days to determine effects on survival and reproduction. Also, the kinetics of uptake and elimination of Ag were studied for F. candida exposed in Lufa 2.2 soil to Ag-NP (at 168 mg Ag/kg dry soil) and AgNO3 (at 30 and 60 mg Ag/kg dry soil). AgNO3 was toxic with an LC50 was 284 mg Ag/kg dry soil for effects on survival and EC10 and EC50 values of 47.6 and 99.5 mg Ag/kg dry soil, respectively for the effect on reproduction. These values did correspond with porewater concentrations of 0.801, 0.042 and 0.082 mg Ag/l, respectively. No effects on survival and reproduction of Ag-NP were observed up to 673 mg Ag/kg dry soil, although porewater concentration was similar to the EC50 for AgNO3. Exposure to both Ag forms caused a fast uptake of Ag, but the Ag elimination rate was significantly higher for Ag-NP than for AgNO3. Bioaccumulation factor was higher for AgNO3 (on average 5.64) than for Ag-NP (1.12). These findings indicate that silver ions are more toxic than Ag-NP and have a higher potential to accumulate in F. candida.
Although the prognosis of pediatric acute myeloid leukemia (pAML) has improved, with current survival rates up to 75%, relapse rates remain high. Areas covered: The low number of patients, the heterogeneous genomic landscape of AML, novel diagnostic techniques, divergent available treatment protocols, and dose-limiting toxicity of conventional agents all contribute to the complexity of AML treatment. This review gives an overview of the current clinical challenges with respect to diagnostics, treatment, and supportive care in pAML. Expert commentary: Due to intensified treatment regimens and improved supportive care measures, the outcome for pAML patients has improved substantially over the past years. However, most treatment protocols still rely on conventional chemotherapeutic agents with significant toxicity. Although targeted therapies promise to reduce the need for high doses of conventional agents with a subsequent decrease in toxicity, the effectiveness of these strategies remains unsatisfactory today. International collaborations are needed in order to address the ongoing therapeutic challenges of reducing toxicity while increasing effectivity. Consensus on risk-group classification, a common chemotherapy backbone and evidence-based supportive care guidelines are necessary in this context, at the same time enabling intergroup studies on new agents in subgroups.
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