A Retrospective Analysis of the Therapeutic Outcomes of 117 Neuroblastoma Patients Treated at a Single Pediatric Oncology Center in China.

OBJECTIVE: Recent therapeutic advances have greatly enhanced the survival rates of patients with neuroblastoma (NB). However, the outcomes of neuroblastoma patients in China, particularly those with high-risk (HR) NB, remain limited. METHOD: We retrospectively analyzed the clinical data and outcomes of NB patients who were treated at a tertiary pediatric cancer facility in China between January 2013 and October 2021. RESULTS: A total of 117 NB patients were recruited. Patients with very low-risk (VLR), low-risk (LR), intermediate-risk (IR), and HR-NB patients made up 4%, 27%, 15%, and 54% of total patient population, respectively. Patients diagnosed between 2013 and 2018 were treated according to the protocol of Sun Yat-Sen University Cancer Center and those diagnosed between 2019 and 2021 were treated according to the COG ANBL0531 or ANBL0532 protocol with or without autologous stem cell transplantation (ASCT). The 5-year EFS and OS of all risk groups of patients were 67.29% and 77.90%, respectively. EFS and OS were significantly decreased in patients with higher risk classifications (EFS: VLR/LR vs IR vs HR: 97.22% vs 67.28% vs 51.83%; ***P = .001; OS: VLR/LR vs IR vs HR: 97.06% vs 94.12% vs 64.38%; *P = .046). In HR-NB patients treated according to the COG protocol between 2019 and 2021, the 3-year OS of patients who received tandem ASCT was significantly greater than those who did not receive ASCT (93.33% % vs 47.41%; *P = .046; log-rank test). EFS was not significantly different between patients with and without ASCT (72.16% vs 60.32%). CONCLUSION: Our findings show that patients with lower risk classification have a positive prognosis for survival. The prognosis of patients with HR-NB remains in need of improvement. ASCT may enhance OS in HR-NB patients; however, protocol adjustment may be necessary to increase EFS in these patients.

Retracted: WNT974 Inhibits Proliferation, Induces Apoptosis, and Enhances Chemosensitivity to Doxorubicin in Lymphoma Cells by Inhibiting Wnt/b-Catenin Signaling.

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Senmin Chen, Xiuli Yuan, Huanli Xu, Meng Yi, Sixi Liu, Feiqiu Wen. WNT974 Inhibits Proliferation, Induces Apoptosis, and Enhances Chemosensitivity to Doxorubicin in Lymphoma Cells by Inhibiting Wnt/b-Catenin Signaling. Med Sci Monit, 2020; 26: e923799. DOI: 10.12659/MSM.923799.

[Changes of intestinal flora in children with acute lymphoblastic leukemia before and after chemotherapy]. / å„¿ç«¥æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— åŒ–ç–—å‰åŽè‚ é“èŒç¾¤å˜åŒ–ç‰¹ç‚¹.

OBJECTIVES: To examine the changes of intestinal flora in children newly diagnosed with acute lymphoblastic leukemia (ALL) and the influence of chemotherapy on intestinal flora. METHODS: Fecal samples were collected from 40 children newly diagnosed with ALL before chemotherapy and at 2 weeks, 1 month, and 2 months after chemotherapy. Ten healthy children served as the control group. 16S rDNA sequencing and analysis were performed to compare the differences in intestinal flora between the ALL and control groups and children with ALL before and after chemotherapy. RESULTS: The ALL group had a significant reduction in the abundance of intestinal flora at 1 and 2 months after chemotherapy, with a significant reduction compared with the control group (P<0.05). Compared with the control group, the ALL group had a significant reduction in the diversity of intestinal flora before and after chemotherapy (P<0.05). At the phylum level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Actinobacteria at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05) and a significant increase in the relative abundance of Proteobacteria at 1 and 2 months after chemotherapy (P<0.05). At the genus level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Bifidobacterium at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05); the relative abundance of Klebsiella in the ALL group was significantly higher than that in the control group at 1 and 2 months after chemotherapy and showed a significant increase at 1 month after chemotherapy (P<0.05); the relative abundance of Faecalibacterium in the ALL group was significantly lower than that in the control group before and after chemotherapy and showed a significant reduction at 2 weeks and 1 month after chemotherapy (P<0.05). The relative abundance of Enterococcus increased significantly at 1 and 2 months after chemotherapy in the ALL group (P<0.05), and was significantly higher than that in the control group (P<0.05). CONCLUSIONS: The diversity of intestinal flora in children with ALL is significantly lower than that in healthy children. Chemotherapy significantly reduces the abundance of intestinal flora and can reduce the abundance of some probiotic bacteria (Bifidobacterium and Faecalibacterium) and increase the abundance of pathogenic bacteria (Klebsiella and Enterococcus) in children with ALL.

circKL inhibits the growth and metastasis of kidney cancer by sponging miR­182­5p and upregulating FBXW7.

Circular RNAs (circRNAs) are a type of non­coding RNA with important roles in the regulation of various biological processes involved in malignant progression. However, the potential molecular mechanisms and roles of circRNAs in kidney cancer have remained to be fully elucidated. In a previous study by our group, high­throughput microarray sequencing data were analyzed to determine the differentially expressed circRNAs in kidney cancer. In this analysis, a novel circRNA (hsa_circ_0100312, named circKL) was identified as a frequently downregulated circRNA in kidney cancer cells and tissues by reverse transcription­quantitative PCR. In the present study, Cell Counting Kit­8, colony formation, Transwell, wound­healing and mouse xenograft assays as well as a lung metastasis experiment were performed to confirm the functions of circKL. The experiments confirmed that circKL overexpression significantly inhibited the proliferation, migration, tumor growth and metastasis of kidney cancer both in vitro and in vivo. The potential molecular mechanisms of circKL were investigated by performing dual­luciferase and RNA immunoprecipitation assays. Western blot assays confirmed that overexpression of circKL significantly increased the protein level of F­box and WD repeat domain containing 7 (FBXW7). All results suggested that circKL suppressed the growth and migration of kidney cancer by sponging microRNA (miR)­182­5p and upregulating FBXW7 expression. Overall, the circKL/miR­182­5p/FBXW7 axis was indicated to have a key role in the growth and metastasis of kidney cancer and may be targeted as a novel therapeutic strategy.

Case Report: Myeloid Sarcoma Development During Treatment for B Cell Lymphoblastic Lymphoma in a Boy with KRAS/NRAS Gene Mutations.

Here, we report a rare case of a 12-year-old boy who was initially diagnosed with B cell lymphoblastic lymphoma (BLBL) and developed myeloid sarcoma (MS) eight months after chemotherapy. Next-generation sequencing (NGS) showed mutations of KRAS and NRAS genes in both the bone marrow and lymph node. He presented an abnormal karyotype of 46, XY, -9, der (16) t (9; 16) (q13; q12), +mar. He received chemotherapy according to the South China Children's Leukemia Group 2016 protocol. Complete remission was achieved by the 15th day post-treatment. Eight months later and immediately prior to the start of maintenance therapy, the patient developed fever, skin nodules in both upper arms, and enlargement of bilateral testes. Pathological analysis of skin and testicular biopsies suggested the diagnosis of myeloid sarcoma (MS). Again, NGS examination showed mutations of KRAS and NRAS genes. The patient underwent haploidentical hematopoietic stem cell transplantation but unfortunately did not survive. The interval of eight-month interval between the initial disease onset and MS brings into question whether MS developed as part of the initial onset of disease or as a secondary tumor in association with chemotherapy. Thus, understanding the pathogenesis of MS involving abnormalities of lymphoid progenitors may assist in the prediction of prognosis and development of novel target therapies.

Evaluation of Inflammatory Biomarkers in Pediatric Hematology-Oncology Patients With Bloodstream Infection.

Bloodstream infection (BSI) is a serious complication in pediatric hematology-oncology patients. To evaluate the clinical significance of C-reactive protein (CRP), procalcitonin (PCT), albumin, fibrinogen, and D-dimer as potential biomarkers to differentiate among various subtypes of BSIs in pediatric patients with hematologic and oncologic diseases, we retrieved and analyzed the medical records of pediatric hematology-oncology patients diagnosed with BSI at our hospital between January 2016 and December 2017. The demographic (sex and age) and clinical (primary diseases) characteristics, and laboratory test results (white blood cell and absolute neutrophil counts, and serum CRP, PCT, albumin, fibrinogen, and D-dimer levels) were compared between nosocomial and non-nosocomial; neutropenic and non-neutropenic; and Gram-positive and Gram-negative BSI episodes. A total of 125 BSI episodes were included, including 69 (55.2%) nosocomial cases, 94 (75.2%) neutropenic cases, and 49 (39.2%) Gram-positive episodes. Of the 5 potential biomarkers evaluated (CRP, PCT, albumin, fibrinogen, and D-dimer), PCT levels were significantly lower in neutropenic episodes and Gram-positive BSIs (P=0.008 and P=0.001, respectively). At a cutoff value of 0.67 ng/mL, the diagnostic sensitivity, specificity, and positive/negative predictive values of PCT for the differentiation of Gram-positive and Gram-negative bacterial sepsis were 74.2%, 64.6%, 70.8%, and 65.2%, respectively. We concluded that PCT might potentially serve as a biomarker to differentiate between Gram-positive and Gram-negative BSIs in pediatric hematology-oncology patients.

WNT974 Inhibits Proliferation, Induces Apoptosis, and Enhances Chemosensitivity to Doxorubicin in Lymphoma Cells by Inhibiting Wnt/ß-Catenin Signaling.

BACKGROUND Upregulation of the Wnt/ß-catenin pathway has been demonstrated to promote tumor proliferation and chemoresistance in lymphoma. Our objective was to evaluate the effect of the Wnt/ß-catenin pathway inhibitor WNT974 in lymphoma cells. MATERIAL AND METHODS Human lymphoma cell lines HUT-78 and BJAB were treated with or without 1 µM WNT974±0.15 µg/L doxorubicin (Dox). Cell viability and proliferation were evaluated by CCK-8 and colony formation assay. Expression of proliferating cell nuclear antigen (PCNA), KI67, and apoptotic-related proteins including Bcl-2, Bax, cleaved-caspase3, and cleaved-caspase9, together with Wnt pathway proteins Wnt, ß-catenin, Axin2, and c-Myc, were detected by Western blot analysis. Flow cytometry was used to calculate the ratio of apoptotic cells. RESULTS In HUT-78 and BJAB cells, 1 µM WNT974 significantly reduced viability and colony formation. The expression of 2 markers of tumor cell proliferation, protein PCNA and KI67, was also reduced by WNT974. Treatment with 1 µM WNT974 for 48 h increased the rate of cell apoptosis, inhibited the expression of anti-apoptotic protein Bcl-2, and enhanced pro-apoptotic proteins Bax, cleaved-caspase3, and cleaved-caspase9 expression in both cell lines. After treatment with WNT974 plus Dox, cell viability was markedly decreased compared with Dox treatment alone. Mechanistically, WNT974 prevented the expression of Wnt, Axin2, ß-catenin, and its target gene c-Myc. CONCLUSIONS WNT974 effectively treats lymphoma by inhibiting cell proliferation, inducing cell apoptosis, and enhancing chemosensitivity to Dox, and these effects are dependent on blocking Wnt/ß-catenin signaling.

Etiology, drug sensitivity profiles and clinical outcome of bloodstream infections: A retrospective study of 784 pediatric patients with hematological and neoplastic diseases.

Bloodstream infections (BSI) represent one of the most serious complications in patients in the hematology-oncology unit. In this study, the prevalence, distribution, drug sensitivity profiles, and clinical outcome of BSI were analyzed in pediatric patients with hematological malignancies. Patients admitted to the pediatric hematology-oncology unit at Shenzhen Children's Hospital (Shenzen, China) between January 2016 and December 2017 were enrolled. Their medical records, including gender, age, primary diseases, and microbiology results of all clinical specimens, were reviewed. The incidence of BSI, microbiology characteristics, and effectiveness of antimicrobial therapy were analyzed. A total of 125 BSI cases in 108 patients (mean age, 5.5 years) were recorded, of which 69 (55.2%) were nosocomial BSI cases. The overall rate of BSI was 18.8% in the hematology-oncology unit, of which 75 (75.2%) episodes were neutropenic patients. Patients with nosocomial BSIs and the neutropenic group were older (p#.02, p#.03). HSCTs and AML were more often observed in nosocomial BSIs, while solid tumors were more found in nonnosocomial and non-neutropenic BSIs. BSIs were dominated by Gram-negative pathogens (49.6%) in the hematology-oncology unit compared with Gram-positive pathogens (39.2%). The most common pathogens were coagulase-negative Staphylococcus (24.2%) followed by Klebsiella pneumonia (15.2%), Escherichia coli (12.5%), viridans streptococci (8.2%), and Candida species (7.8%). The antibiotic therapy success rate in patients was 93.5%. Based on our center's experience, Gram-negative pathogens were commonly observed among pediatric hematology-oncology patients with BSI. Coagulase-negative Staphylococcus and K. pneumoniae predominated and antibiotic therapy was effective in these patients.

Hypermethylation of p15 gene associated with an inferior poor long-term outcome in childhood acute lymphoblastic leukemia.

PURPOSE: To quantitate methylation of the CpG island of the promoter region of the p15 gene in childhood acute lymphoblastic leukemia (ALL) and explore its effect on prognosis. METHODS: We assessed methylation of the CpG island on the p15 gene in bone marrow mononuclear cells in 93 ALL cases and in a control group of 20 children with idiopathic thrombocytopenia (ITP) by restriction enzyme Eco52I digestion combined with polymerase chain reaction techniques. We explored the effect of varying levels of methylation on event-free survival (EFS). RESULTS: The mean methylation level was 25 % in de novo ALL and significantly higher than the control group 2 %, P < 0.01). Forty-two percent of cases (39/93) had hypermethylation (level over 10 %). Fifty-seven percent (12/21) and 38 % (27/72) T- and precursor-B ALL patients had hypermethylation (not significant). For all patients, the 8-year EFS was (83 ± 4) %, standard risk (91 ± 4) %, intermediate risk (IR) (82 ± 5) %, and high risk (HR) (43 ± 19) % (χ(2) = 11.58, P < 0.01). Hypermethylation was associated with a lower 8-year EFS (71 ± 7 vs. 91 ± 4 %, P = 0.02) in univariate analyses. CONCLUSIONS: Children with ALL have higher levels of p15 CpG island methylation than a control group of children with ITP. Among children with ALL, hypermethylation was associated with inferior EFS. Higher levels of p15 CpG island methylation may be a poor prognostic marker in childhood ALL.