Excellent Early Outcomes of Combined Chemotherapy With Arsenic Trioxide for Stage 4/M Neuroblastoma in Children: A Multicenter Nonrandomized Controlled Trial.

This nonrandomized, multicenter cohort, open-label clinical trial evaluated the efficacy and safety of combined chemotherapy with arsenic trioxide (ATO) in children with stage 4/M neuroblastoma (NB). We enrolled patients who were newly diagnosed with NB and assessed as stage 4/M and received either traditional chemotherapy or ATO combined with chemotherapy according to their own wishes. Twenty-two patients were enrolled in the trial group (ATO combined with chemotherapy), and 13 patients were enrolled in the control group (traditional chemotherapy). Objective response rate (ORR) at 4 weeks after completing induction chemotherapy was defined as the main outcome, and adverse events were monitored and graded in the meantime. Data cutoff date was December 31, 2019. Finally, we found that patients who received ATO combined with chemotherapy had a significantly higher response rate than those who were treated with traditional chemotherapy (ORR: 86.36% vs. 46.16%, p=0.020). Reversible cardiotoxicity was just observed in three patients who were treated with ATO, and no other differential adverse events were observed between the two groups. ATO combined with chemotherapy can significantly improve end-induction response in high-risk NB, and our novel regimen is well tolerated in pediatric patients. These results highlight the superiority of chemotherapy with ATO, which creates new opportunity for prolonging survival. In addition, this treatment protocol minimizes therapeutic costs compared with anti-GD2 therapy, MIBG, and proton therapy and can decrease the burden to families and society. However, we also need to evaluate more cases to consolidate our conclusion.

Gene Mutation Spectrum of Thalassemia Among Children in Yunnan Province.

Background: Thalassemia is an autosomal genetic disorder, found throughout the world. It is still not treatable and create socio economic problems. In this study, we investigated the prevalence and spectrum features of thalassemia in Yunnan Province, the southwestern area of China. During 2014-2018, a total of 3,539 suspected thalassemia children were detected with α- and ß-thalassemia mutations by gap-Polymerase Chain Reaction (PCR) and reverse dot blot (RDB) analysis in Kunming Children's Hospital. Results: Of these patients, 1,130 were diagnosed thalassemia gene carriers with a carrying rate of 31.92%. Among them, α-thalassemia was 43.63%, ß-thalassemia was 53.98%, cases with both α- and ß- thalassemia was 2.39%. In α-thalassemia patients, the most common mutations was -SEA/αα (52.13%), followed by -α3.7/αα (27.79%), hemoglobin H disease (18.46%), and -α4.2/αα (1.62%). Fifteen gene mutations and 30 genotypes were identified in ß-thalassemia patients, with the five most common mutations CD17 (A>T) (29.51%), CD41-42 (-TTCT) (27.87%), IVS-II-654 (C>T) (14.92%), CD26 (G>A) (6.89%), and CD26/CD27 (2.62%) accounting for 81.81% of the ß-globin gene mutations. Furthermore, we founded two rare mutations CD34 (TGG → TAG) and Int in Chinese populations. Conclusions: Our results suggested that the prevalence and gene mutation spectrum of thalassemia display obviously heterogeneity among children in Yunnan Province. The findings provide the valuable information for premarital and pre-pregnancy screening, prenatal diagnostic services, and designing appropriate prevention programs to control thalassemia for future in this area.

A de novo ANK1 mutation associated to hereditary spherocytosis: a case report.

BACKGROUND: Hereditary spherocytosis (HS) is a type of hemolytic anemia caused by abnormal red cell membrane skeletal proteins with few unique clinical manifestations in the neonate and infant. An ANK1 gene mutation is the most common cause of HS. CASE PRESENTATION: The patient was a 11-month-old boy who suffered from anemia and needed a regular transfusion therapy at an interval of 2-3 months. Hematological investigations showed moderate anemia (Hb80 g/L). Red cells displayed microcytosis (MCV76.4 fl, MCH25.6 pg, MCHC335 g/L). The reticulocytes were elevated (4.8%) and the spherocytes were increased (10%). Direct antiglobulin test was negative. Biochemical test indicated a slight elevation of bilirubin, mainly indirect reacting (TBIL32.5 µmol/L, IBIL24 µmol/L). The neonatal HS ratio is 4.38, obviously up the threshold. Meanwhile, a de novo ANK1 mutation (exon 25:c.2693dupC:p.A899Sfs*11) was identified by next-generation sequencing (NGS). Thus, hereditary spherocytosis was finally diagnosed. CONCLUSIONS: Gene detection should be considered in some hemolytic anemia which is difficult to diagnose by routine means. We identified a novel de novo ANK1 heterozygous frameshift mutation in a Yi nationality patient while neither of his parents carried this mutation.