Background: Prompt response to induction chemotherapy is a prognostic factor in pediatric acute myeloid leukemia. In this study, we aimed to evaluate the prognostic significance of multiparametric flow cytometry-minimal residual disease (MFC-MRD), assessed at the end of the first and second induction courses. Methods: MFC-MRD was performed at the end of the first induction (TP1) in 524 patients and second induction (TP2) in 467 patients who were treated according to the modified Medical Research Council (UK) acute myeloid leukemia 15 protocol. Results: Using a 0.1% cutoff level, patients with MFC-MRD at the two time points had lower event-free survival and overall survival. Only the TP2 MFC-MRD level could predict the outcome in a separate analysis of high and intermediate risks based on European LeukemiaNet risk stratification and KMT2A rearrangement. The TP2 MFC-MRD level could further differentiate the prognosis of patients into complete remission or non-complete remission based on morphological evaluation. Multivariate analysis indicated the TP2 MFC-MRD level as an independent adverse prognostic factor for event-free survival and overall survival. When comparing patients with MFC-MRD ≥ 0.1%, those who underwent hematopoietic stem cell transplant during the first complete remission had significantly higher 5-year event-free survival and overall survival and lower cumulative incidence of relapse than those who only received consolidation chemotherapy. Conclusions: The TP2 MFC-MRD level can predict the outcomes in pediatric patients with acute myeloid leukemia and help stratify post-remission treatment.

Background: A high ecotropic viral integration site 1 (EVI1) expression (EVI1^high) is an independent prognostic factor in adult acute myeloid leukemia (AML). However, little is known of the prognostic value of EVI1^high in pediatric AML. This study aimed to examine the biological and prognostic significance of EVI1^high in uniformly treated pediatric patients with AML from a large cohort of seven centers in China.Methods: A diagnostic assay was developed to determine the relative EVI1 expression using a single real-time quantitative polymerase chain reaction in 421 newly diagnosed pediatric AML patients younger than 14 years from seven centers in southern China. All patients were treated with a uniform protocol, but only 383 patients were evaluated for their treatment response. The survival data were included in the subsequent analysis (n = 35 for EVI1^high, n = 348 for EVI1^low).Results: EVI1^high was found in 9.0% of all 421 pediatric patients with de novo AML. EVI1^high was predominantly found in acute megakaryoblastic leukemia (FAB M7), MLL rearrangements, and unfavorable cytogenetic aberrance, whereas it was mutually exclusive with t (8; 21), inv (16)/t (16; 16), CEBPA, NPM1, or C-KIT mutations. In the univariate Cox regression analysis, EVI1^high had a significantly adverse 5-year event-free survival (EFS) and overall survival (OS) [hazard ratio (HR) = 1.821 and 2.401, p = 0.036 and 0.005, respectively]. In the multivariate Cox regression analysis, EVI1^high was an independent prognostic factor for the OS (HR = 2.447, p = 0.015) but not EFS (HR = 1.556, p = 0.174). Furthermore, EVI1^high was an independent adverse predictor of the OS and EFS of patients with MLL rearrangements (univariate analysis: HR = 9.921 and 7.253, both p < 0.001; multivariate analysis: HR = 7.186 and 7.315, p = 0.005 and 0.001, respectively). Hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) provided EVI1^high patients with a tendential survival benefit when compared with chemotherapy as a consolidation (5-year EFS: 68.4% vs. 50.8%, p = 0.26; 5-year OS: 65.9% vs. 54.8%, p = 0.45).Conclusion: It could be concluded that EVI1^high can be detected in approximately 10% of pediatric AML cases. It is predominantly present in unfavorable cytogenetic subtypes and predicts adverse outcomes. Whether pediatric patients with EVI1^high AML can benefit from HSCT in CR1 needs to be researched further.

Summary: Studies on asparaginase enzyme activity (AEA) monitoring in Chinese patients receiving PEG‐asparaginase remain limited. We monitored AEA in paediatric patients diagnosed with acute lymphoblastic leukaemia (ALL) and treated according to the Chinese Children's Cancer Group study protocols, CCCG‐ALL‐2015/CCCG‐ALL‐2020 protocols. We measured the AEA at days 7 ± 1 and 14 ± 1 and analysed their association with patient characteristics and PEG‐asparaginase‐related adverse effects (AEs). We measured 2147 samples from 329 patients. Mean AEA levels (interquartile range) were 931 iu/L (654–1174 iu/L) at day 7 ± 1 and 664 iu/L (463–860 iu/L) at day 14 ± 1. The AEA levels were higher in younger children and increased with the cumulative dose numbers. PEG‐asparaginase inactivation rate was 19.1%, and the silent inactivation (SI) rate was 12.5%. Nine patients were identified with allergic‐like reactions. Hypofibrinogenaemia, hypertriglyceridaemia, pancreatitis and thrombosis were associated with older age, whereas hypoglycaemia was associated with younger age. The risk of hypertriglyceridaemia and hypoglycaemia increased with cumulative dose numbers of PEG‐asparaginase. Except for hypofibrinogenaemia, elevated AEA levels did not increase the risk of PEG‐asparaginase‐related AEs. Drug monitoring can be utilized as guidance for treatment decision‐making. Individualizing asparaginase doses do not reduce toxicities. The treatment target of PEG‐asparaginase remains to achieve sustained and adequate activity.

The present study aimed to investigate the real-world results of childhood acute lymphoblastic leukemia (cALL) cases in Fujian, China. The clinical data of 1414 patients with newly diagnosed cALL in Fujian were retrospectively analyzed. Patients were treated according to the Chinese Children Leukemia Group 2008 protocol (CCLG-ALL 2008 group) or Chinese Children's Cancer Group 2015 protocol (CCCG-ALL 2015 group). Cumulative incidence of treatment abandonment (TA) at 5 years was 4.2% +/- 0.6% and significantly associated with treatment period and risk stratification. The 5-OS and EFS were significantly higher in the CCCG-ALL 2015 group than in the CCLG-ALL 2008 group. Patients treated with CCCG-ALL 2015 from Fujian Medical Union Hospital had a significantly higher 4-year OS and EFS than did those from the other four hospitals. Real-world TA of cALL greatly decreased, and its long-term survival significantly increased in Fujian, which may be related to optimizing programs, multi-center collaboration, and improving treatment compliance.