Efficacy and safety of zinc in the prevention of oral mucositis in children with cancer receiving intensified chemotherapy: A randomized double-blind placebo-controlled trial.

BACKGROUND AND AIMS: A limited number of safe and effective preventive options for oral mucositis (OM) are available. This randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy and safety of zinc in preventing OM in children with cancer receiving intensified chemotherapy. METHODS: Children aged 3-18 years were randomized to receive oral zinc at 1 mg/kg/dose daily for 14 days or a placebo at the same doses and schedule. The primary outcome of this study was to determine the effect of oral zinc in the prevention of OM, and secondary outcomes included any adverse effect of oral zinc, the severity and duration of OM, and the need for hospitalizations. RESULTS: A total of 90 children were randomized to either the oral zinc (n = 44) or placebo group (n = 46). The incidence of OM in the zinc group was 20.5%, while that in the placebo group was 19.6% (p = .91; risk ratio: 1.04, 95% CI 0.45-2.30). There were no significant adverse events of the drug observed. There were no significant differences between the two groups in the severity (p = .79), the mean time of onset (p = .09), the mean duration of OM (p = .18), and the need for hospitalizations (p = 1.0). CONCLUSIONS: Among children on cancer chemotherapy, there was no decrease in the incidence of OM observed with oral zinc at a dose of 1 mg/kg/day. No significant adverse events were observed with administering oral zinc. Further research is warranted to test higher doses of oral zinc with longer duration for a clinically significant effect.

Acute myeloid leukemia: novel mutations and their clinical implications.

Acute myeloid leukemia (AML) is a heterogenous and challenging hematological malignancy with suboptimal outcomes. The implications of advanced technologies in the genetic characterization of AML have enhanced the understanding of individualized patient risk, which has also led to the development of new therapeutic strategies. A comprehensive study of novel mutations is essential to moderate the complicacies in patient management and achieve optimal outcomes in AML. In this review, we summarized the clinical relevance of important novel mutations, including TET2, ETV6, SATB1, EZH2, PTPN11, and U2AF1, which impact the prognosis of AML. TET2 mutation can lead to DNA hypermethylation, and gene fusion, and mutation in ETV6 disrupts hematopoietic transcription machinery, SATB1 downregulation aggravates the disease, and EZH2 mutation confers resistance to chemotherapy. PTPN11 mutation influences the RAS-MAPK signaling pathway, and U2AF1 alters the splicing of downstream mRNA. The systemic influence of these mutations has adverse consequences. Therefore, extensive research on novel mutations and their mechanism of action in the pathogenesis of AML is vital. This study lays out the perspective of expanding the apprehension about AML and novel drug targets. The combination of advanced genetic techniques, risk stratification, ongoing improvements, and innovations in treatment strategy will undoubtedly lead to improved survival outcomes in AML.

Molecular evaluation of gene mutation profiles and copy number variations in pediatric acute myeloid leukemia.

BACKGROUND: The objectives of this study were to investigate the mutation profiles of targeted genes and copy number variations (CNVs) in normal cytogenetics (CN) pediatric acute myeloid leukemia (AML). METHODS: This prospective study was conducted from October 2018 to December 2020. The next-generation sequencing (NGS) and chromosomal microarray analyses (CMA) were performed in pediatric CN-AML patients. RESULTS: Out of 94 children (aged ≤18 years), 70 patients with AML (24 excluded) underwent conventional karyotyping/cytogenetic analyses. Forty-five (64.3%) of patients had abnormal/ recurrent cytogenetic abnormalities and 25 (35.7%) had normal cytogenetics. Twenty-three out of 25 CN-AML were further processed for gene mutation profile and CNVs using NGS and CMA, respectively. Twenty-two out of 23 (95.7%) patients were detected to have mutations in various genes. The common mutations were: NRAS, NPM1, CEBPA, KRAS, KIT, RUNX1, NOTCH1, WT1, GATA1, GATA2, FLT3, KMT2D, FLT3-TKD, and PHF6. Copy number variations (CNVs) were detected in nine patients (39%), and eight (34.8%) had a long contiguous stretch of homozygosity (LCSH) /loss of heterozygosity (LOH). An LCSH was detected on chromosomes 5, 7, 11, and 19. The gains were more common than losses (8 vs 2). The gains were observed on chromosomes 8, 9, 14, 19, 21, and 22, and the losses were detected on chromosomes 7 and 10. Monosomy was observed in three patients. Three patients (monosomy7, n = 2, and FLT-ITD, n = 1) were reclassified into the high-risk category. Post-induction, complete remission was achieved in all evaluable patients. CONCLUSION: CN-AML patients have genetic abnormalities that can be detected by more advanced techniques like NGS and CMA. These genetic abnormalities play a role in risk stratification that may remain hidden in otherwise CN-AML.

A comprehensive analysis of cytogenetics, molecular profile, and survival among pediatric acute myeloid leukemia: a prospective study from a tertiary referral center.

BACKGROUND AND AIMS: The objectives of this study were to investigate the cyto-molecular profile and survival of pediatric acute myeloid leukemia (AML). METHODS: This prospective study was carried out in a tertiary care hospital from October 2018 to December 2020. Karyotype and cytogenetics analyses were done to identify chromosomal aberrations in pediatric AML. The targeted molecular panel utilized the polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR), and fragment analysis. RESULTS: A total of 70 patients of AML with aged ≤18 years were enrolled in this study. The cytogenetic analyses revealed abnormal/recurrent cytogenetic abnormalities (CA) in 64.3% of patients and normal cytogenetics (CN) in 35.7% of patients. FAB M2 subtype showed frequent aberrant expression of the CD19 marker. CD7, CD11b, and CD36a were significantly present in the absence of molecular markers. Common chromosomal abnormalities were t(translocation) (8;21) (55%), monosomy/deletion 7 (13%), monosomal karyotype (5%) and complex karyotype (3%). The fusion transcripts RUNX1-RUNX1T1 [t(8;21)] (41%) and CBFB-MYH11 [t(16;16)] (3%) were detected by RT-PCR and FLT3-TKD D835 mutation (1.5%) by allele-specific oligo PCR. Fragment analysis revealed NPM1 (8%) mutation and FLT-ITD (9.5%) mutations. Complete remission was achieved in all evaluable patients. The median follow-up period of our patients was 225 days (IQR 28; 426 days). The median event-free survival (EFS) in all patients was 11.9 months (95% CI, 5-12.6 months). The forty months overall survival probability (pOS) was 58% in all patients. CONCLUSION: The majority of patients had abnormal/recurrent cytogenetics abnormalities. FAB M2 subtype showed frequent aberrant expression of the CD19. The absence of molecular markers may suggest the presence of CD7, CD11b, and CD36a expression. The overall survival has increased considerably in LMIC.