Epidemiological evaluation and survival of children with acute myeloid leukemia

Morais, Rahuany Velleda de; Souza, Meriene Viquetti de; Silva, Klerize Anecely de Souza; Santiago, Pablo; Lorenzoni, Marcelo Cunha; Lorea, Cecília Fernandes; Castro, Cláudio Galvão de; Taniguchi, Adriano Nori Rodrigues; Scherer, Fernanda; Michalowski, Mariana Bohns; Daudt, Liane Esteves

doi:10.1016/j.jped.2020.02.003

Cited by 8 publications

(12 citation statements)

References 29 publications

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“…A high WBC count at initial diagnosis ( > 100×10 9 /L) is generally associated with a worse prognosis. 3,10,11 Some cytogenetic findings including t(8;21), t(15;17), inv( 16), AML1-ETO, CEBPA, NPM1, and trisomy 21 are associated with favorable prognosis, 8,15 whereas MLL rearrangements and c-kit mutation are related with poor prognosis. 2,3,11,13 Although its association with clinical outcome unknown, EMI is known to be related with genetic abnormalities such as c-kit mutation, 11q23 abnormalities involving MLL gene, t(8;21), inv (16), and NPM1, in addition to several other factors such as <1 year, male sex, and central nervous system disease, whereas inconsistent relationship is seen between EMI and the recognized prognostic factors of AML including WBC counts at diagnosis and FLT3-ITD.…”

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

“…Pediatric acute myeloid leukemia (AML) accounts for about 5% of pediatric malignancies1 and 15% to 25% of pediatric acute leukemia 2–4. The reported cure rates range from 60% to 70% in the developed countries,2,3 and the disease causes more than half of the leukemic deaths in children 4. Although the prognosis of pediatric AML has been improved by risk group classification based on cytogenetics and early treatment response,2,4 further investigations on risk factors to achieve better clinical outcomes are still ongoing 1…”

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confidence: 99%

“…6 The incidence of EMI in adults with AML is reported as 2% to 5%, while it is significantly more frequently found, about 7% to 49% in pediatric AML patients. 3,[9][10][11]13 The definition in terms of accepted inclusion criteria and prognostic role of EMI is still controversial, 7,10,14,15 and there is even more limited information in the pediatric population. 2 There is a lack of consensus in various studies whether hepatosplenomegaly and lymph node involvement should be considered as EMI, 3,15,16 some arguing that those findings should not be regarded as EMI since they are a manifestation of organ infiltration by myeloblasts rather than discrete mass formation.…”

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confidence: 99%

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Extramedullary Infiltration in Pediatric Acute Myeloid Leukemia on Surveillance Magnetic Resonance Imaging and its Relationship With Established Risk Factors

Kim

Im²,

Lee

et al. 2021

Journal of Pediatric Hematology/Oncology

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Purpose: Extramedullary infiltration (EMI) is a rare condition defined by the accumulation of myeloid tumor cells beyond the bone marrow. The clinical significance is still controversial. This study was aimed to evaluate the incidence, characteristics, and prognostic significance of EMI on complete magnetic resonance imaging (MRI) investigation in newly diagnosed pediatric acute myeloid leukemia (AML) patients who are asymptomatic without clinical evidence to suspect EMI.Materials and Methods: Retrospective clinical and radiologic review of 121 patients with MRI examination at the time of initial diagnosis of AML without any clinical evidence suggestive of EMI was performed. Patients were divided into 2 groups according to the presence or absence of EMI, and the relationship between EMI and established risk factors was analyzed. Initial white blood cell count, the occurrence of an event (including relapse, death, and primary refractory disease), survival status, and detailed information on cytogenetic/molecular status was performed by a thorough review of electronic medical records system. All patients underwent full imaging evaluation with the contrast-enhanced whole body and some regional MRI at the time of initial diagnosis. Results:The median age at diagnosis was 10.77 years (range, 0.37 to 18.83 y). Based on the risk stratification system of AML, 36, 45, and 40 patients are classified as low-risk, intermediate-risk, and high-risk groups, respectively. MRI at the time of the initial diagnosis of AML revealed 35 of 121 patients (28.9%) with EMI. The most common site of EMI was a skull, followed by the lower extremity bone and meninges of the brain. The median age at diagnosis was significantly younger in patients with EMI (7.87 vs. 11.08 y, P = 0.0212). Low incidence of FLT3/ITD mutation, low incidence of AML-ETO gene rearrangement, and the larger extent and more severe degree of bone marrow involvement was related with EMI. However, there was no significant prognostic difference in eventfree survival and overall survival regardless of the presence of EMI in the overall patient population and each risk group. The location of EMI occurrence was also not related to prognosis.Conclusions: Even if EMI symptoms are not evident, surveillance MRI scans at the initial diagnosis of pediatric AML patients are very helpful in detecting a significant number of EMIs. Younger age, some molecular features, and more severe bone marrow involvement of AML patients were related with EMI. However, there was no significant prognostic difference between patients with or without EMI regardless of risk group. Further prospective investigation is necessary to validate the prognostic effect of EMI in a larger group of patients with different risk groups.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Extramedullary Infiltration in Pediatric Acute Myeloid Leukemia on Surveillance Magnetic Resonance Imaging and its Relationship With Established Risk Factors

Kim

Im²,

Lee

et al. 2021

Journal of Pediatric Hematology/Oncology

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“…Acute myeloid leukemia (AML) is a molecularly heterogeneous disease that is defined by the uncontrolled rapid expansion of immature myeloid blast cells. AML is the deadliest acute leukemia in children, with an overall survival rate of only 70%, which has not substantially improved for decades [1]. Multiple rounds of chemotherapy remain the gold standard treatment option for AML, although current therapies lack specificity against leukaemic cells and severely affect healthy tissues [2].…”

Section: Introductionmentioning

confidence: 99%

Development of siRNA-Loaded Lipid Nanoparticles Targeting Long Non-Coding RNA LINC01257 as a Novel and Safe Therapeutic Approach for t(8;21) Pediatric Acute Myeloid Leukemia

et al. 2021

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Standard of care therapies for children with acute myeloid leukemia (AML) cause potent off-target toxicity to healthy cells, highlighting the need to develop new therapeutic approaches that are safe and specific for leukemia cells. Long non-coding RNAs (lncRNAs) are an emerging and highly attractive therapeutic target in the treatment of cancer due to their oncogenic functions and selective expression in cancer cells. However, lncRNAs have historically been considered ‘undruggable’ targets because they do not encode for a protein product. Here, we describe the development of a new siRNA-loaded lipid nanoparticle for the therapeutic silencing of the novel oncogenic lncRNA LINC01257. Transcriptomic analysis of children with AML identified LINC01257 as specifically expressed in t(8;21) AML and absent in healthy patients. Using NxGen microfluidic technology, we efficiently and reproducibly packaged anti-LINC01257 siRNA (LNP-si-LINC01257) into lipid nanoparticles based on the FDA-approved Patisiran (Onpattro®) formulation. LNP-si-LINC01257 size and ζ-potential were determined by dynamic light scattering using a Malvern Zetasizer Ultra. LNP-si-LINC01257 internalization and siRNA delivery were verified by fluorescence microscopy and flow cytometry analysis. lncRNA knockdown was determined by RT-qPCR and cell viability was characterized by flow cytometry-based apoptosis assay. LNP-siRNA production yielded a mean LNP size of ~65 nm with PDI ≤0.22 along with a >85% siRNA encapsulation rate. LNP-siRNAs were efficiently taken up by Kasumi-1 cells (>95% of cells) and LNP-si-LINC01257 treatment was able to successfully ablate LINC01257 expression which was accompanied by a significant 55% reduction in total cell count following 48 h of treatment. In contrast, healthy peripheral blood mononuclear cells (PBMCs), which do not express LINC01257, were unaffected by LNP-si-LINC01257 treatment despite comparable levels of LNP-siRNA uptake. This is the first report demonstrating the use of LNP-assisted RNA interference modalities for the silencing of cancer-driving lncRNAs as a therapeutically viable and non-toxic approach in the management of AML.

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Screening and validating circular RNAs that estimate disease risk and treatment response of pediatric acute myeloid leukemia: a microarray-based analyses and RT-qPCR validation

Ye,

Fan,

Peng

et al. 2023

J Cancer Res Clin Oncol

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Epidemiological evaluation and survival of children with acute myeloid leukemia

Cited by 8 publications

References 29 publications

Extramedullary Infiltration in Pediatric Acute Myeloid Leukemia on Surveillance Magnetic Resonance Imaging and its Relationship With Established Risk Factors

Extramedullary Infiltration in Pediatric Acute Myeloid Leukemia on Surveillance Magnetic Resonance Imaging and its Relationship With Established Risk Factors

Development of siRNA-Loaded Lipid Nanoparticles Targeting Long Non-Coding RNA LINC01257 as a Novel and Safe Therapeutic Approach for t(8;21) Pediatric Acute Myeloid Leukemia

Screening and validating circular RNAs that estimate disease risk and treatment response of pediatric acute myeloid leukemia: a microarray-based analyses and RT-qPCR validation

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