Background: Neuroblastoma (NBL) is the most common extra-cranial solid tumour in childhood, with prognosis ranging from spontaneous remission to high risk for rapid and fatal progression. Despite existing therapy approaches, the 5-year event-free survival (EFS) for patients with advanced NBL remains below 30%, emphasizing urgent necessary for novel therapeutic strategies. Studies have shown that epigenetic disorders play an essential role in the pathogenesis of NBL. However, the function and mechanism of N7-methylguanosine (m⁷G) methyltransferase in NBL remains unknown. Methods: The expression levels of m⁷G tRNA methyltransferase Methyltransferase-like 1 (METTL1) were analyzed by querying the Gene Expression Omnibus (GEO) database and further confirmed by immunohistochemistry (IHC) assay. Kaplan-Meier, univariate and multivariate cox hazard analysis were performed to reveal the prognostic role of METTL1. Cell function assays were performed to evaluate how METTL1 works in proliferation, apoptosis and migration in cell lines and xenograft mouse models. The role of METTL1 on mRNA translation activity of NBL cells was measured using puromycin intake assay and polysome profiling assay. The m⁷G modified tRNAs were identified by tRNA reduction and cleavage sequencing (TRAC-seq). Ribosome nascent-chain complex-bound mRNA sequencing (RNC-seq) was utilized to identify the variation of gene translation efficiency (TE). Analyzed the codon frequency decoded by m⁷G tRNA to clarify the translation regulation and mechanism of m⁷G modification in NBL. Results: This study found that METTL1 were significantly up-regulated in advanced NBL, which acted as an independent risk factor and predicted poor prognosis. Further in NBL cell lines and BALB/c-nu female mice, we found METTL1 played a crucial role in promoting NBL progression. Furthermore, m⁷G profiling and translation analysis revealed downregulation of METTL1 would inhibit puromycin intake efficiency of NBL cells, indicating that METTL1 did count crucially in regulation of NBL cell translation. With all tRNAs with m⁷G modification identified in NBL cells, knockdown of METTL1 would significantly reduce the levels of both m⁷G modification and m⁷G tRNAs expressions. Result of RNC-seq shew there were 339 overlapped genes with impaired translation in NBL cells upon METTL1 knockdown. Further analysis revealed these genes contained higher frequency of codons decoded by m⁷G-modified tRNAs and were enriched in oncogenic pathways. Conclusion: This study revealed the critical role and mechanism of METTL1-mediated tRNA m⁷G modification in regulating NBL progression, providing new insights for developing therapeutic approaches for NBL patients.

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As₄S₄), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

Invasive fungal infection (IFI) is life-threatening in children with cancer and hematology disorders, especially when diagnosis and treatment are delayed. Conventional β-D-glucan and galactomannan tests have poor positive predictive values in the diagnosis of IFI in children with cancer. This study aims to access the diagnostic performance of C-reactive protein (CRP) and procalcitonin (PCT) in differentiating IFI from bacterial bloodstream infections in children with malignant and hematology disorders. CRP and PCT levels were measured in samples taken from patients between 12 and 24 h after fever onset, of which 24 and 102 were in the IFI and bacterial groups, respectively. We found that the CRP levels were much higher in the IFI group than the bacterial group (100.57 versus 40.04 mg/L, median, p < 0.001), while the PCT levels remained significantly lower (0.45 versus 1.29 μg/L, median, p = 0.007). Both CRP and PCT showed significant diagnostic utilities with an area under the curve (AUC) of 0.780 (95% CI, 0.664–0.896, p < 0.001) and 0.731 (95% CI, 0.634–0.828, p < 0.001) when using the cut-off values of 94.93 mg/L and 2.00 μg/L, respectively. However, the combined biomarker of CRP and PCT yielded a better diagnostic performance with an AUC of 0.934 (95% confidential interval (CI), 0.881–0.987, p < 0.001), which was significantly higher than that of CRP or PCT (both p < 0.001), with a sensitivity of 87.5% and a specificity of 87.3%. Our study demonstrates high levels of CRP combined with low PCT could differentiate IFI from bacterial bloodstream infections in immunocompromised children.

Background: Treatment outcomes for acute promyelocytic leukemia (APL) have improved with all-trans-retinoic acid and arsenic trioxide, yet relapse remains a concern, especially in pediatric patients. The prognostic value of minimal residual disease (MRD) post-induction and the impact of arsenic levels during induction on MRD are not fully understood. Objectives: To evaluate the relationship between post-induction MRD levels and relapse-free survival (RFS) in pediatric APL patients, and to investigate the correlation between blood arsenic concentration levels during induction therapy and MRD status. Design: A retrospective analysis of pediatric APL patients enrolled in a clinical trial from September 2011 to July 2020. Methods: We assessed the relationship between RFS and post-induction MRD levels using the log-rank test. The optimal MRD cut-off was determined using the “surv_cutpoint” function in the survminer R package. Arsenic concentration levels were monitored in 16 patients on days 7 and 14 of induction therapy, and Spearman correlation was used to analyze the relationship between arsenic concentrations and MRD levels. Results: Among 176 pediatric APL patients, with a median follow-up of 6 years, 4 relapsed. Patients with MRD >3.1% had significantly lower RFS compared to those with MRD ⩽3.1% (94.6% vs 100%, p = 0.023). In addition, a negative correlation was found between blood arsenic concentration levels and post-induction MRD levels. Lower arsenic concentrations were associated with higher MRD levels, with significant correlations observed for trough concentrations ( R = −0.666, p = 0.005) and peak concentrations ( R = −0.499, p = 0.049) on day 7. Conclusion: Our study highlights the prognostic significance of post-induction MRD assessment in pediatric APL. We also demonstrate a negative correlation between blood arsenic concentration levels and MRD, suggesting that lower arsenic concentrations during induction therapy may contribute to a higher MRD burden. These findings may inform strategies to optimize treatment and improve outcomes in pediatric APL. Trial registration: www.clinicaltrials.gov (NCT02200978).

Voriconazole is a second-generation azole widely used for the prevention and treatment of fungal infection in leukemia patients. We report a case of 9-year-old girl with T-cell acute lymphoblastic leukemia who developed hallucinations and visual disturbance after using voriconazole twice. These symptoms began acutely after treatment with voriconazole and resolved rapidly when the voriconazole was stopped. No specific cause was identified, and thus the symptoms were considered to be the adverse drug reactions (ADRs) of voriconazole. Simultaneous development of hallucinations and visual disturbance caused by voriconazole in children rarely have been reported before and the causes of these ADRs are unknown. Several other cases of hallucinations and (or) visual disturbance caused by voriconazole among 15–81 years old patients have been reported in the literature, and are reviewed. Those patients reminded us of the importance of being aware of hallucinations and visual disturbance associated with voriconazole treatment. In addition, we speculate that the hallucinations and visual disturbance are not related to the dosage form of voriconazole. We emphasize that it is also important to monitor the concentration of voriconazole regularly to avoid potential toxicity.