A clinical report on high­dose cytarabine therapy for children with acute myeloid leukemia.

Despite improvement in the long-term survival rate following pediatric acute myeloid leukemia (AML), the rate remains low, even with optimal treatment. The present study reports the long-term outcome of a small patient group treated with a single drug, high-dose chemotherapy (HDCT) with cytarabine, including consolidation and maintenance therapy. RT-PCR was conducted to assess 43 fusion genes, and after treatment, all cases have been followed up for 20 years (June 2002-December 2020). With an 80% 5-year survival rate, the results of this study highlight the possibility that pediatric AML can be reasonably effectively treated with relatively simple chemotherapy when necessary. HDCT is clinically safe, effective and relatively inexpensive. We propose that in the context of limited resources, HDCT should be considered as an alternative therapy for pediatric AML.

Eukaryotic initiation factor-2, gamma subunit, suppresses proliferation and regulates the cell cycle via the MAPK/ERK signaling pathway in acute myeloid leukemia.

PURPOSE: The expression of eukaryotic translation initiation factor-2 subunit 3 (EIF2S3) in patients with non-small cell lung and colorectal cancer is lower than that in healthy individuals. However, the functions of EIF2S3 remain unclear, and its study in leukemia has not been reported. The article aims to explore the role of EIF2S3 in AML (acute myeloid leukemia) and its underlying mechanism. METHODS: Reverse transcription-quantitative PCR was performed to evaluate the expression levels of EIF2S3, and its association with patient prognosis was determined. Inducible HEL-EIF2S3 and HL-60-EIF2S3 cell lines were established by retrovirus infection. Cellular proliferation and the cell cycle were analyzed using Cell Counting Kit-8 and flow cytometric analyses. Tumorigenic ability was evaluated using xenograft nude mouse model. Gene expression profiles were analyzed in HL-60-EIF2S3 cells by next-generation sequencing, and WB analysis was performed to detect the expression of related proteins. RESULTS: The expression of EIF2S3 in patients with AML was lower than that experiencing CR (P = 0.02). Furthermore, EIF2S3 overexpression inhibited cellular proliferation, halted G0/1 to S phase cell cycle progression, and inhibited tumorigenicity (P = 0.015). 479 differentially expressed genes were identified between HL60-EIF2S3 DOX (-) and HL60-EIF2S3 DOX ( +) cells via NGS and several of them involved in MAPK/ERK signaling pathway. The phosphorylation levels of ERK decreased when EIF2S3 was overexpressed (P < 0.050). CONCLUSION: EIF2S3 overexpression may result in a decrease in cellular proliferation, cell cycle arrest, and tumorigenic inhibition via the MAPK/ERK signaling pathway in AML cells.

Effects of programmed death ligand 1 on the prognosis of neuroblastoma: A protocol for systematic review and meta analysis.

BACKGROUND: Previous studies have investigated the prognostic role of programmed death ligand 1 (PD-L1) expression in patients with neuroblastoma, while the results are still controversial. Therefore, we conducted a meta-analysis to clarify the relationship between the expression of PD-L1 and the prognosis of neuroblastoma. METHODS: Search electronic databases include PubMed, Cochrane, Embase, Scopus and Web of Science, and the search time is set to build the database until January 2021. Hazard ratio (HR) and 95% confidence interval (CI) were used to analyze the included results. Meta-analysis was performed using Stata 15.0 software. RESULTS: This review will be disseminated in print by peer-review. CONCLUSION: The study will provide updated evidence for the evaluation of whether the expression of PD-L1 is associated with poor prognosis in patients with neuroblastoma. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/FBCY6.

Status and prognostic nomogram of patients with Burkitt lymphoma.

The purpose of the present study was to evaluate the newest status of patients diagnosed Burkitt lymphoma (BL), an aggressive lymphoma subset with a high cure rate. Furthermore, the study aimed to create prognostic nomograms to consider various prognostic factors and estimate patient survival, paving the way for clinical decision-making. A total of 4,600 patients diagnosed with BL between 1983 and 2015 were investigated, via data collected from the SEER database. The overall status of the patients was analyzed through several aspects, including incidence and survival analysis of the previous three decades using the log-rank test and the Kaplan-Meier method. In order to construct and validate the nomograms, the patient diagnosed during 2005-2015 were randomly assigned to the training cohort and validation cohort. Univariate and multivariate analyses were applied to identify independent factors that were further included in the nomograms, predicting 3- and 5-year overall survival (OS) and cancer-specific survival (CSS). The data of the training cohort were used for internal validation and validation cohort used to external validation. C-index and calibration plots were used to validate the nomograms, comparing predicted values with actual outcomes. The incidence of BL was gradually increased from 1984 and reached its peak in 2009, at a rate of 0.491 per 100,000 [95% confidence interval (CI), 0.412-0.581]. From 2009, the incidence slowly declined year by year and dropped to 0.280 per 100,000 (95% CI, 0.224-0.346). The OS and CSS rates of patients diagnosed between 2005 and 2015 were increased, in contrast with those of patients diagnosed from 1983-1993 and 1994-2004. A total of five variables, including age, race, chemotherapy, primary site and stage, proved to be the prognostic factors of BL and were used to construct the nomograms predicting 3- and 5-year OS and CSS. The internal and external calibration plots for the probability of 3- and 5-year OS and CSS were consistent between nomogram prediction and observed outcomes. The slow decline in incidence and the significantly improved cure rate make BL a disease that is no longer an urgent problem. Effective nomograms were developed to predict the OS and CSS of patients with BL.

A Literature Review of Blood-Disseminated P. marneffei Infection and a Case Study of this Infection in an HIV-Negative Child with Comorbid Eosinophilia.

BACKGROUND: The typical manifestations of Penicillium marneffei (nowadays Talaromyces marneffei) infection in children without human immunodeficiency virus (HIV) remain unclear. The current work presents the case of a child without an underlying disease who was infected with P. marneffei comorbid with eosinophilia. CASE PRESENTATION: A 2-year-old male was infected with P. marneffei. A physical examination revealed a high-grade fever, ulcerated lesions in the oral mucosa, anemia, pruritic erythematous papules on the sac and thigh and watery diarrhea. A chest enhanced computed tomography scan showed multiple small, nodular, high-density shadows in the lungs, multiple lymphadenectasis in the hilum of the lungs and mediastinum, and liquid in the right pleural cavity. The patient's plasma was negative for HIV. Routine blood tests initially indicated that the patient had leucopenia; however, later tests indicated that he had leukocytosis. This peak was caused by a significant increase in eosinophils. The total IgE and specific allergen levels were normal. The stool was negative for parasite eggs. Aspergillus antigen (galactomannan, GM) levels were significantly increased and were present in the serum for a relatively long period. CONCLUSIONS: Eosinophilia can occur during P. marneffei infection, and this finding might provide additional information on the activity of this intracellular parasite. In addition, GM detection might be useful for monitoring the effect of antifungal treatments; however, this theory requires more data for verification.

[Effects of acute lymphoblastic leukemia children bone marrow mesenchymal stem cells on drug resistance of K562/A02 cell line].

The aim of study was to investigate the effect of acute lymphoblastic leukemia (ALL) children bone marrow mesenchymal stem cells (MSC) on resistance of K562/A02 cells and its mechanism. MSC obtained from bone marrow of AL children were cultured and identified. The co-culture of MSC and K562/A02 and the culture of K562/A02 cell suspension alone was performed, of which 2 kinds of cells were treated with same concentration of adriamycin (ADM), and the rate of apoptosis was detected by flow cytometry, bcl-2 and bax of K562/A02 were detected by RT-PCR, while mdr1 gene level was detected by FQ-PCR. The results indicated that the MSC separation and proliferation were viable and steady. The apoptosis rate of the K562/A02 cells co-cultured with MSC was 1.97 ± 0.11%, while apoptosis rate of the K562/A02 cells cultured alone was 8.38 ± 0.29%, there was significant difference (p < 0.05). As compared with the K562/A02 cells cultured alone, the bcl-2 gene expression in K562/A02 cells co-cultured with MSC obviously increased; ratio of bcl-2/bax was obviously enhanced. The mdr1 gene level in K562/A02 co-cultured with MSC was no statistical different from K562/A02 cultured alone (p > 0.05), which suggested that adhesion co-cultured with MSC did not induce mdr1 expression higher than the culture of suspension. It is concluded that the MSC of ALL children can escape the leukemia cells from proapoptotic effect of drugs, the resistance of K562/A02 to ADM may be involved in enhancement of bcl-2 gene expression of K562/A02 cells co-cultured with MSC, but not in relation to mdr1 gene in K562/A02 cells themselves.

[Preliminary study on the safety and pharmacodynamic action of low dose L-asparaginase].

OBJECTIVE: To investigate the safety and therapeutic effect of low dose (1000 U/m(2)) L-asparaginase (L-Asp) in the treatment of children with acute lymphoblastic leukemia (ALL). METHODS: Six patients were treated with low dose L-Asp after previously suffered severe side effects from standard dose L-Asp (5000 - 10,000 U/m(2)). Twenty-eight blood samples were obtained randomly from 5 of them. Plasma asparagine concentration was detected by reverse phase-high performance liquid chromatography (RP-HPLC). RESULTS: All the patients treated with low dose L-Asp showed no any toxic symptoms. The plasma asparagine levels in the patients were all above 5 micromol/L except case 4 (4.91 micromol/L) before receiving L-Asp, and were all decreased below 0.5 micromol/L five days after receiving low dose L-Asp, except case 3 (3.70 micromol/L), the results being like that of receiving standard dose L-Asp. CONCLUSION: Low dose L-Asp has definite efficacy for childhood ALL, while avoids serious side effects from standard dose L-Asp.

[Detection of mdr1 gene by real-time fluorescence quantitative polymerase chain reaction using Taq Man-MGB probe].

OBJECTIVE: Primer Express 2.0 software was used to design the primers and the MGB probe. With the plasmid pHaMDR1/A containing mdr1 cDNA as the template, we established a real-time fluorescent quantitative polymerase chain reaction system, which, at the template concentration of 3.061 x 10(3) to 3.061 x 10(9) cps/ml, had a correlation coefficient of 0.988243 between template concentration and threshold cycle value. This PCR method allows sensitive, specific and quantitative detection of human mdr1 gene.

[Research on the pharmacokinetics and pharmacodynamics of L-asparaginase during its treatment of childhood acute lymphoblastic leukemia].

OBJECTIVE: To investigate the changes in the activity of Escherichia coli asparaginase (L-asp) and the concentration of asparagines (ASN) in the plasma of the acute lymphoblastic leukemia (ALL) children receiving L-asp containing chemotherapeutic protocol to explore more reasonable usage of L-asp in the treatment of childhood ALL. METHODS: L-asp containing hemotherapy regimen of VDLP was used, in which L-asp (10,000 U/m(2)) was administered intravenously every other day for 10 doses in 15 children with ALL. A total of 340 peripheral blood samples were collected at scheduled time points during the therapy and plasma L-asp activity (by spectrophotometric assay) and asparagines concentration (by RP-HPLC) were measured. RESULTS: During the administration of L-asp, the plasma L-asp activity was increasing gradually peaked after eight doses and then decreased gradually, while the plasma concentration of asparagines maintained in complete or nearly complete depletion status. After the therapy courses finished, a plasma L-asp activity above 100 U/L with asparagines almost complete depletion status was lasting for about seven days. CONCLUSION: The current L-asp containing chemotherapeutic protocols in which L-asp was administered in a dose of 10 000/m(2) intravenously every other day, are efficient enough for the depletion of plasma ASN.