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Children with acute myeloid leukemia (AML) commonly develop extramedullary disease (EMD), which comprises central nervous system (CNS) lesions and myeloid sarcoma (MS). In this retrospective analysis, we aimed to determine the effect of EMD on the outcomes of allogeneic hematopoietic cell transplantation (HCT) in 678 pediatric patients with de novo AML (median age, 7 years; range, 0.3-15 years) between 2006 and 2016. We compared the outcomes between patients with (EMD group, n = 158; CNS lesion, n = 47, CNS lesion + MS, n = 9, and MS, n = 102) and without EMD at diagnosis (non-EMD group, n = 520). Survivors were followed for a median of 4.5 years, and the 4-year overall survival (OS) rates were 60.6% and 56.4% in the EMD and non-EMD groups, respectively (P = 0.60). No significant differences in OS were observed with respect to the EMD site, except bone lesions, which were associated with poor OS after HCT in a non-remission status. A multivariate analysis revealed that EMD did not affect the outcomes of HCT. In conclusion, the study findings suggest that EMD should not be considered a poor prognostic factor in HCT for children with AML.

Although the 5-year survival rates in pediatric acute myeloid leukemia (AML) have improved over the last decades, there is a high relapse rate for Pediatric AML patients. In the present study, we mainly combine PCA with the LASSO technique to identify prognostic markers for Pediatric AML patients coming from the NCI TARGET database. Three key genes (EEF1A1, RPLP2, RPL19) associated with poor prognosis of pediatric AML has been screened by both PCA and LASSO Cox regression analysis. Simultaneously, we developed a risk score model to predict the prognosis of pediatric AML, according to risk scores, the patients were divided into high‐ and low‐risk groups based on the median risk score. Kaplan–Meier survival analysis indicated that Pediatric AML patients with the high-risk group have a poorer survival rate than those with a low‐risk group (p

Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0–18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996–December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008–2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996–2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1–RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008–2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008–2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008–2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents’ use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.

Background microRNA-381 is dysregulated in a variety of cancers. However, its clinical significance in pediatric acute myeloid leukemia (AML) is still unclear. The purpose of this study was to detect the expression level of miR-381 in pediatric AML patients and to explore its potential clinical significance. Methods The levels of miR-381 in bone marrow and serum of 102 pediatric AML patients were measured by quantitative real-time polymorperase chain reaction (qRT-PCR). The diagnostic value of serum miR-381 in pediatric AML patients was evaluated by the receiver operating characteristic (ROC) curve. A Chi square test was used to analyze the relationship between serum miR-381 and the clinical characteristics of patients. Cox regression analysis and Kaplan–Meier evaluated the prognostic value of serum miR-381 in patients. Finally, the proliferation of the cells was analyzed by the CCK-8 assay. Results Compared with healthy controls, the levels of miR-381 in serum and bone marrow of pediatric AML patients were significantly decreased (P P P = 0.011) and poor relapse-free survival (log-rank test, P = 0.004). Cox regression analysis confirmed that reduced serum miR-381 was an independent predictor of poor prognosis in AML (HR = 3.794, 95% CI 1.3633–10.559, P = 0.011). In addition, low expression of miR-381 significantly reduced the proliferation of cells (P Conclusion All experimental results confirm that miR-381 has reduced bone marrow and serum expression in pediatric AML, and low levels of serum miR-381 have certain diagnostic and prognostic value in pediatric AML and may be a potential therapeutic target for AML.

Pediatric patients with acute myeloid leukemia (AML) are at high risk of invasive fungal infection (IFI). In adult patients, the D-index, which reflects the duration and intensity of neutropenia, was reported as a predictive factor of IFI after induction therapy for AML. The aim of this study was to assess whether the D-index is a predictive factor for IFI in pediatric AML. We define the D-index as the area over the neutrophil curve during neutropenia. Ninety-two courses of chemotherapy performed for 24 consecutive patients with AML undergoing chemotherapy at Sapporo Hokuyu Hospital between April 2007 and March 2017 were analyzed. We also evaluated the utility of the cumulative D-index (c-D-index) from the start of neutropenia until the clinical manifestation of IFI in these patients. The D-index and c-D-index were compared between courses with and without IFI episodes. The median D-index and c-D-index in 6 courses with IFI episodes were 12,816 (range 9500-27,412) and 7250 (range 3987-16,273), respectively, which was not statistically higher than the median D-index [10,127 (range 3788-20,897)] in 86 courses without IFI episodes (P = 0.081 and P = 0.108, respectively). Unlike in adult cases, neither the D-index nor c-D-index reflected the risk of IFI in pediatric AML.

A Children's Oncology Group study of nearly 1,000 pediatric acute myeloid leukemia (AML) cases reveals marked differences between the genomic landscapes of pediatric and adult AML and offers directions for future work.

There is paucity of data in pediatric Acute Myeloid Leukemia (AML) from developing countries. We analyzed the outcomes of 65 consecutive patients with pediatric AML treated at our centre from January-2008 to May-2013. The median event free survival (EFS) and overall survival (OS) were 12.6 and 14.6 months respectively. Patients with good-risk cytogenetics had a better EFS (p = 0.004) and OS (p = 0.01). Overall, these results are not comparable to that observed in other centres globally and leaves scope for further improvement. This includes implementing allogeneic bone marrow transplantation as a treatment for all children with high-risk AML.

Background Since the early 1990s, three consecutive pediatric acute myeloid leukemia (AML) trials have been performed in Austria (AML-Berlin-Frankfurt-Münster (BFM) 93, AML-BFM 98, and AML-BFM 2004) in close cooperation with the international BFM study center. Herein, we review the pertinent patient characteristics, therapy, and outcome data. Patients and methods From January 1993 to April 2013, 249 children and adolescents (193 protocol patients) diagnosed with AML were enrolled in the three BFM studies. Patients were mainly treated in one of five pediatric hematology/oncology centers distributed over Austria. Results Many characteristics and outcome parameters were not statistically different between the three trials. Almost similar proportions of patients were stratified into two risk groups: standard risk (SR) (approximately 37 % overall) and high-risk (HR) (61 %). MLL rearrangements were found in 23 % of patients overall as the most frequent genetic aberration subtype. Complete remission (CR) was achieved by 84–95 % of patients. The most important type of event was leukemic relapse (5-year cumulative incidence 40 ± 8 %, 21 ± 5 %, and 39 ± 6 %; p = 0.058), with a trend to a higher rate specifically in SR patients of study AML-BFM 2004 compared with AML-BFM 98. Importantly, the frequency of death from causes other than relapse sequelae declined over the years (AML-BFM 93: 5/42 12 %, AML-BFM 98: 5/57 9 %, and AML-BFM 2004: 5/94 5 %). Altogether, event-free survival at 5 years varied insignificantly (48 ± 8 %, 61 ± 7 %, and 50 ± 6 %; p = 0.406). Nevertheless, survival (pSU) apparently improved from BFM 93 to subsequent studies, both overall (57 ± 8 %, 75 ± 6 %, and 62 ± 6 %; p = 0.046) and regarding the HR group (5-year-probability of survival (pSU) 40 ± 10 %, 66 ± 8 %, and 52 ± 8 %; p = 0.039). Conclusion Treatment of pediatric AML in Austria renders survival rates in the range of international best practice. However, unambiguous statistical comparison of treatment periods is eventually hampered by small numbers and inequalities of recruitment. Hence, only internationally collaborative trials will allow developing treatment further to achieve higher cure rates with fewer events.

Childhood acute myeloid leukemia (AML) represents about 20 % of acute childhood leukemias. Today, the 5-year overall survival rates are close to 70 %. The outcome of childhood AML has significantly improved in the last few decades, secondary to: a better understanding of etiology and risk factors; identification of prognostic factors and their incorporation in treatment protocols; the development of novel therapeutic agents based on cytogenetic and molecular information; implementation of supportive care using evidence-based medicine; and an emphasis on the importance of close follow-up and management of late effects. Further advances in AML management can only occur through continued efforts to understand the disease, and the design of international clinical trials with larger patient groups where novel therapies and treatment protocols can be evaluated.

Stable and reproducible engraftment of primary adult and pediatric acute myeloid leukemia in NSG mice

Extensive mutational status of genes and clinical outcome in pediatric acute myeloid leukemia

Acute myelocytic leukemia (AML) is a heterogeneous disease that accounts for nearly a quarter of the pediatric leukemias. Despite near myeloablative therapy, half of patients relapse and die from their disease. Identification of patients at high risk of relapse early in the course of treatment may allow for treatment modification to improve their outcome. In addition, patients at lower risk of relapse may benefit from treatment de-escalation, sparing them adverse side effects. This review describes prognostic factors that play a major role in the outcome of children with AML and their potential use for treatment stratification in pediatric AML trials.

Impact of genetic variation in FKBP5 on clinical response in pediatric acute myeloid leukemia patients: a pilot study

N822 mutation of KIT gene was frequent in pediatric acute myeloid leukemia patients with t(8;21) in Japan: a study of the Japanese childhood AML cooperative study group

No nucleophosmin mutations in pediatric acute myeloid leukemia with normal karyotype: a study of the Japanese Childhood AML Cooperative Study Group