BackgroundAtrial septal defect often become more severe when encountered in genetic syndromes. Congenital disorder of glycosylation type 1a is an inherited metabolic disorder associated with mutations in PMM2 gene and can affect almost all organs. Cardiac abnormalities vary greatly in congenital disorder of glycosylation type 1a and congenital heart defects have already been reported, but there is little knowledge about the effect of this inherited disorder on an existing congenital heart defect. Herein we report for the first time on a baby with congenital disorder of glycosylation type 1a with atrial septal defect and make a comparison of changes in atrial septal defect by follow-ups to the age of 3.Case presentationOur patient was an 8-month-old Han Chinese boy. At the initial visit, he presented with recurrent lower respiratory infection, heart murmur, psychomotor retardation, inverted nipples, and cerebellar atrophy. Echocardiography revealed a 8 mm secundum atrial septal defect with left-to-right shunt (Qp/Qs ratio 1.6). Enzyme testing of phosphomannomutase 2 demonstrated decreased levels of phosphomannomutase 2 activities in fibroblasts. Whole exon sequencing showed he was heterozygous for a frameshift mutation (p.I153X) and a missense mutation (p.I132T) in PMM2 gene. The diagnosis of congenital disorder of glycosylation type 1a with atrial septal defect was issued. Now, he is 3-years old at the time of this writing, with the development of congenital disorder of glycosylation type 1a (cerebellar atrophy become more severe and the symptom of nystagmus emerged), the size of atrial septal defect increased to 10 mm and the Qp/Qs ratio increased to 1.9, which suggested exacerbation of the atrial septal defect. Congenital heart defect-associated gene sequencing is then performed and shows there are no pathogenic mutations, which suggested intrinsic cardiac factors are not the cause of exacerbation of the atrial septal defect in our patient and it is reasonable to assume congenital disorder of glycosylation type 1a can worsen the situation of the existing atrial septal defect.ConclusionsThis report highlights the view that congenital disorders of glycosylation type 1a should be excluded when faced with congenital heart defect with cerebellar atrophy or neurodevelopmental delay, especially when the situation of congenital heart defect becomes more and more severe.

Activating FLT3 mutations are the most common mutations in acute myeloid leukemia (AML), but the optimal threshold of FLT3/ITD allelic ratio (AR) among pediatric AML patients remains controversial. Here, we present the outcome and prognostic significance of FLT3/ITD AR analysis among pediatric patients with AML from the TARGET dataset. Applying fitting curve models and threshold effect analysis using the restrictive cubic spline function following Cox proportional hazards models identifies the cut-off value of 0.5 on FLT3/ITD AR. Moreover, we observe that high FLT3/ITD AR patients have an inferior outcome when compared to low AR patients. Our study also demonstrates that stem cell transplantation may improve the outcome in pediatric AML patients with high FLT3/ITD AR and may be further improved when combined with additional therapies such as Gemtuzumab Ozogamicin. These findings underline the importance of individualized treatment of pediatric AML.

The purpose of this study is to examine the safety and efficacy of eltrombopag as first-line treatment for thrombocytopenia among paediatric patients after haematopoietic stem cell transplantation (HSCT). Methods: Forty-three childhood patients with thrombocytopenia after HSCT who received eltrombopag were retrospectively analysed. Result: Eltrombopag was began at the median of 27 days after HSCT and lasted for 24 days. Thirty-five children responded to eltrombopag therapy, and the cumulative platelet recovery rate was 88.9%. The cumulative incidence of platelet recovery was lower (83.9 vs 100%; P = .035) in patients with decreased numbers of megakaryocytes before starting eltrombopag than in those with normal. Factors associated with a significantly elevated response to eltrobopag from univariate analysis were donor type. Results from the multiple regression analysis found that weight (hazard ratio [HR] = 0.7, 95% confidence interval [CI] 0.5-0.9, P = .022), platelet engraftment time (HR = 1.0, 95%CI 1.0-1.0, P = .012) and bone marrow megakaryocytes (HR = 8.0, 95%CI 1.5-43.3, P = .016) before starting eltrombopag were the independent risk factors. Based on Youden's index algorithm in the receiver-operating characteristic curve, the optimal cutoff value of the maintenance dose of eltrombopag in predicting nonresponders was 4 mg/kg. The area under the receiver-operating characteristic curve was 0.923 with sensitivity of 97.8%, specificity of 87.9%, positive predictive value of 72.3%, and negative predictive value of 92%. None of the paediatric patients stopped using eltrombopag due to side effect or intolerability. Conclusion: Eltrombopag is effective and safe in paediatric patients with thrombocytopenia after HSCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may serve as a predictor of the response to eltrombopag. We recommend that the maintenance dose of eltrombopag should not exceed 4 mg/kg/d. Kun-yin Qiu and Xiong-yu Liao contributed equally to this work Dun-hua Zhou and Jian-pei Fang: these corresponding authors have contributed equally to this work The study has been approved by Sun Yat-sen Memorial Hospital Ethics Committee (China).

Objective The purpose of our study was to evaluate the diagnostic value of serum galactomannan antigen (GM) testing combined with chest computed tomography (CT) of invasive pulmonary aspergillosis (IPA) in pediatric patients after hematopoietic stem cell transplantation. Methods A retrospective nested case‐control study was conducted in the identifying IPA among pediatric patients. Results A total of 141 eligible pediatric recipients with febrile neutropenia were enrolled in this study. All patients in the cases were diagnosed with proven‐probable IPA(PP‐IPA), while only 9 patients in the controls. GM testing was positive in 38 pediatric recipients in the cases and nine recipients in the controls with sensitivity of 62.3%, specificity of 81.8%. Among all patients with IPA, 46 patients in the cases and 9 patients in the controls had typical features of CT imaging with sensitivity of 79.3%, specificity of 85.2%. For discrimination of participants' GM testing combined with CT evaluation, the AUC of the diagnostic model was 0.887 with PPV of 0.764, and NPV of 0.872. Sensitivity was 0.793, and specificity was 0.852 in IPA. Conclusion The combination methods with serum GM and CT scan might be used as a valuable marker for early diagnosis of IPA in pediatric patients after HSCT.

X-linked hyper-immunoglobulin M (IgM) syndrome is characterized by recurrent infections, low or undetectable levels of IgG and IgA, and normal to increased serum IgM, and is also rare. It is associated with mutation in the gene encoding CD40 ligand. This study aimed to describe the first international report of hemizygous CD40LG c.542G>A mutation in a 5-year-old boy with a phenotype of Crohn's disease and hemophagocytic lymphohistiocytosis. Also, the clinical implications of this mutation and associated atypical phenotype are discussed.

To evaluate the outcome and prognostic significance of CEBPA mutations among pediatric acute myeloid leukemia (AML) from TARGET dataset. A total of 1803 pediatric patients who were diagnosed with AML were classified into two groups based on the CEBPA status by using a retrospective cohort study method from September 1996 to December 2016. The incidence of CEBPA mutations was 18%.CEBPA mutations were significantly associated with elder age (p < 0.001), higher WBC (p = 0.004), higher proportion of peripheral blood blast (p < 0.001), normal karyotype (p < 0.001), low risk (p < 0.001) and higher complete remission induction rates (p < 0.05). Overall, CEBPA mutations patients had a significantly better 5-year EFS (p < 0.001) and OS (p < 0.001) compared to CEBPA wild-type patients, and this favorable impact was maintained even in the presence of FLT3/ITD mutations. Stem cell transplantation had no significant impact on the survival of patients with coexistence of CEBPA and FLT3/ITD mutations. Multivariate analysis demonstrated that mutated CEBPA were an independent favorable indicators of better outcome in terms of EFS (p = 0.007) and OS (p = 0.039). Our study demonstrate mutated CEBPA have an excellent outcome in pediatric AML patients. Furthermore, pediatric AML patients with coexistence of CEBPA and FLT3/ITD mutation appear to have favorable prognoses and might not required stem cell transplantation.

Background Invasive fungal disease (IFD) has a poor prognosis in children with hematological disorders after hematopoietic stem cell transplantation (HSCT). We assessed if drug combinations with different targets may improve the outcome. Methods Retrospective study to assess the outcome of combination antifungal therapy (CAT) for proven‐probable IFD (PP‐IFD) in children with hematological disorders after HSCT from January 2008 to June 2018. Results Over the 10‐year period, 95 PP‐IFD were diagnosed in pediatric recipients, median age of 5.6 years. Twenty‐seven patients received combinations of caspofungin and voriconazole, 28 patients received combinations of caspofungin and amphotericin B, and 40 patients received combinations of voriconazole and amphotericin B. The overall response rate of PP‐IFD was 77.9%, while the 100‐day overall survival rates were 66.8%. Univariate analysis showed that factors that significantly affected the response to combination treatments were type of combination (P = 0.02), the stem cell source (P = 0.04), the donor type (P = 0.03), HLA‐match (P = 0.03), aGVHD (P = 0.02), period of treatment (P = 0.044), use of corticosteroids (0.036), CD4:CD8 ratio (P = 0.014), and CMV viremia (P = 0.033). In addition, multivariate analysis demonstrated that only the type of combination remained a significant factor (odds ratio = 0.335, 95% confidence interval: 0.071‐0.812, P = 0.042). Forty‐three children suffered from mild and reversible adverse reactions, no serious side effects during treatment. Conclusion A variety of factors can affect the outcome of CAT. Combination of caspofungin with voriconazole is a safe and helpful treatment option for HSCT recipients with IFD.

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