Long-term follow-up of haploidentical haematopoietic stem cell transplantation in paediatric patients with high-risk acute myeloid leukaemia: Report from a single centre.

Data from 200 children with high-risk acute myeloid leukaemia who underwent their first haploidentical haematopoietic stem cell transplantation (haplo-HSCT) between 2015 and 2021 at our institution were analysed. The 4-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 71.9%, 62.3% and 32.4% respectively. The 100-day cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease (aGVHD) were 41.1% and 9.5% respectively. The 4-year cumulative incidence of chronic GVHD (cGVHD) was 56.1%, and that of moderate-to-severe cGVHD was 27.3%. Minimal residual disease (MRD)-positive (MRD+) status pre-HSCT was significantly associated with lower survival and a higher risk of relapse. The 4-year OS, EFS and CIR differed significantly between patients with MRD+ pre-HSCT (n = 97; 63.4%, 51.4% and 41.0% respectively) and those with MRD-negative (MRD-) pre-HSCT (n = 103; 80.5%, 73.3% and 23.8% respectively). Multivariate analysis also revealed that acute megakaryoblastic leukaemia without Down syndrome (non-DS-AMKL) was associated with extremely poor outcomes (hazard ratios and 95% CIs for OS, EFS and CIR: 3.110 (1.430-6.763), 3.145 (1.628-6.074) and 3.250 (1.529-6.910) respectively; p-values were 0.004, 0.001 and 0.002 respectively). Thus, haplo-HSCT can be a therapy option for these patients, and MRD status pre-HSCT significantly affects the outcomes. As patients with non-DS-AMKL have extremely poor outcomes, even with haplo-HSCT, a combination of novel therapies is urgently needed.

Retrospective analysis of data from 73 patients with childhood acute promyelocytic leukaemia receiving modified chemotherapy: a single-centre study.

PURPOSE: Early death (ED) and treatment-related toxicity emerge as two major barriers for curing paediatric acute promyelocytic leukaemia (APL) patients. This study aims to investigate the effect of idarubicin on controlling hyperleukocytosis in induction therapy and the efficacy and safety of a risk-adapted attenuated consolidation chemotherapy. METHODS: We summarised the characteristics and long-term outcomes of 73 paediatric APL patients treated at our institution from February 2002 to October 2018, during which treatment protocols evolved over three periods and were defined as protocol A, B and C chronologically. All of the patients received an all-trans retinoic acid (ATRA)-arsenic trioxide (ATO) combination remission induction therapy, with hydroxyurea (group A) or idarubicin (group B and C) to control hyperleukocytosis. Consolidation chemotherapy was modified with risk-adapted attenuated intensity and minimised cumulative doses of anthracyclines for group C (144 mg/m2 and 288 mg/m2 of daunorubicin equivalents for standard- and high-risk patients, respectively). RESULTS: The median initial WBC, platelet count, and fibrinogen were 2.9 × 109/L (range 0.9-158.3 × 109/L), 32 × 109/L (range 4-226 × 109/L), and 160 mg/dL (range 53-549 mg/dL), respectively. High-risk and standard-risk were seen in 20.5% and 79.5% of patients, respectively. Three patients (4.1%) suffered early haemorrhagic death. At the end of induction therapy, 68 (93.2%) patients achieved haematologic complete remission (HCR). At a median follow-up of 91.97 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates for the whole cohort were 95.9 ± 2.3% and 88.7 ± 3.8%, respectively. A comparison of HCR rates and documented instances of toxicity between groups A and B + C showed no significant differences. However, idarubicin significantly reduced the peak WBC count (Z = - 3.292, P = 0.001) and duration of hyperleukocytosis (Z = - 2.827, P = 0.005). Estimated 3-year EFS (91.7 ± 8.0%) and OS (100%) rates for group C were not significantly different from those for group B, whereas the risk of treatment-related infections was significantly reduced (χ2 = 5.515, P = 0.019). CONCLUSIONS: Idarubicin (8-10 mg/m2/day for 2 days) for hyperleukocytosis control in induction therapy is safe and effective for paediatric APL. Risk-adapted attenuated consolidation chemotherapy is advocated.

Clinical and pathogenic analysis of 507 children with bacterial meningitis in Beijing, 2010-2014.

OBJECTIVES: To explore the clinical characteristics and analyze the pathogens of bacterial meningitis in children. METHODS: Bacterial meningitis cases occurring from January 2010 through December 2014 at Beijing Children's Hospital were reviewed retrospectively. The records of all patients, including data on clinical features and laboratory information, were obtained and analyzed. RESULTS: In total, the cases of 507 pediatric patients seen over a 5-year period were analyzed; 220 of these cases were etiologically confirmed. These patients were classified into four age groups: 29 days to 1 year (n=373, 73.6%), 1-3 years (n=61, 12.0%), 3-6 years (n=41, 8.1%), and >6 years (n=32, 6.3%). The main pathogens identified in this study were Streptococcus pneumoniae (n=73, 33.2%), Escherichia coli (n=24, 10.9%), Enterococcus (n=22, 10.0%), and group B Streptococcus (n=18, 8.2%). All Gram-positive bacteria were sensitive to vancomycin and linezolid. All Gram-negative bacteria were sensitive to meropenem. The total non-susceptibility rate of S. pneumoniae to penicillin was 47.6% (20/42). The resistance rates to ceftriaxone, cefepime, and ceftazidime were 75% (9/12), 55.6% (5/9), and 40% (4/10), respectively. CONCLUSIONS: The main pathogen of bacterial meningitis in this study was S. pneumoniae. The antibiotic resistance rates among children with bacterial meningitis are of serious concern.

[Research methods in protein-protein and protein-nucleic acid interactions and application in the study of human enterovirus A71].

Methods for analyses of protein-protein interactions include: yeast two hybrid (Y2H), phage dis- play (PD), co-immunoprecipitation (Co-IP), glutathione S-transferase pull-down (GST pull-down), cellular co-localization, far-western blotting, virus overlay protein binding assay (VOPBA), surface plasmon resonance (SPR), and fluorescence resonance energy transfer (FRET). Technologies for the detection of protein-nucleic acid interactions include: yeast one hybrid (Y1H), chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), Southwestern blotting, reporter gene, Co-IP, GST pull-down, and PD. These methods are often used in the study of the human enterovirus A71 (EV-A71) by our research team. Reviews in the Chinese literature in this field are lacking, so we reviewed applications of these methods in the study of EV-A71. This review may impart important knowledge in the research of other viruses with regard to protein-protein and protein-nucleic acid interactions.