OBJECTIVES:To investigate the effectiveness of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) in the treatment of children with high-risk neuroblastoma (NB). METHODS:A retrospective analysis was performed on 29 children with high-risk NB who were admitted to Shanghai Children's Hospital and were treated with high-dose chemotherapy combined with ASCT from January 2013 to December 2021, and their clinical features and prognosis were analyzed. RESULTS:Among the 29 children treated by high-dose chemotherapy combined with ASCT, there were 18 boys (62%) and 11 girls (38%), with a median age of onset of 36 (27, 59) months. According to the International Neuroblastoma Staging System, 6 children (21%) had stage III NB and 23 children (79%) had stage IV NB, and the common metastatic sites at initial diagnosis were bone in 22 children (76%), bone marrow in 21 children (72%), and intracalvarium in 4 children (14%). All 29 children achieved reconstruction of hematopoietic function after ASCT. After being followed up for a median time of 25 (17, 45) months, 21 children (72%) had continuous complete remission and 8 (28%) experienced recurrence. The 3-year overall survival rate and event-free survival rate were 68.9%±16.1% and 61.4%±14.4%, respectively. Presence of bone marrow metastasis, neuron-specific enolase ≥370 ng/mL and positive bone marrow immunophenotyping might reduce the 3-year event-free survival rate (P<0.05). CONCLUSIONS:Children with high-risk NB who have bone marrow metastasis at initial diagnosis tend to have a poor prognosis. ASCT combined with high-dose chemotherapy can effectively improve the prognosis of children with NB with a favorable safety profile.

BACKGROUND Hereditary spherocytosis (HS) is characterized by anemia, jaundice, splenomegaly, and cholelithiasis, and is caused by abnormal genes encoding red blood cell membrane components. The most common mutations found in HS are in the ANK1 gene. CASE SUMMARY A 4-mo-old girl was admitted to our hospital with pallor that had lasted for more than 2 mo. She presented with jaundice, anemia and splenomegaly. A heterozygous mutation of ANK1 (exon23: c.G2467T:p.E823X) was identified, and the mutation was determined to be autosomal dominant. This mutation is linked to the relatively serious anemia she had after birth; this anemia improved with age. CONCLUSION The utilization of next-generation sequencing may assist with the accurate diagnosis of HS, especially in atypical cases.

Chimeric antigen receptor T cell (CAR-T) therapy has breakthrough potential for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). However, because of the risk for neurotoxicity, trials usually exclude patients with central nervous system leukemia (CNSL) or active neurological comorbidities (NC). Here, we evaluated the efficacy and neurotoxicity of humanized CD19-directed CAR-T therapy for R/R ALL with CNSL or NC. Of 12 enrolled patients, 4 had CNSL with bone marrow (BM) or testicular recurrence, 3 had BM relapses with NC, and 5 had BM relapse without NC. Bridging chemotherapy was performed for high tumor burden before CAR-T therapy. Patients with CNSL or BM relapse with NC or without NC experienced 100% complete remission. Tumor burden reduction did not occur in 1 patient with NC, who developed grade 5 neurotoxicity before BM assessment, and one patient with CNSL developed leukoencephalopathy. Severe cytokine release syndrome and neurotoxicity developed in 0% with CNSL, 33.3% with BM relapse and NC, and 0% without NC. CAR-T cells expanded in the cerebrospinal fluid (CSF) of all patients with no difference among CNSL, BM with NC, or no NC (respective median percentages among lymphocyte: 33.7%, 48.2% and 34.5%, P =0.899; respective median concentrations: 0.82, 2.21, and 0.46/μL, P =0.719). Median CSF CAR-T cell duration was 5.5 (3-9) months with CNSL and 3 (2-3) months without CNSL ( P =0.031). CAR-T can be given safely and effectively to pediatric patients with R/R ALL with CNSL or NC who have near-normal neurological status. High tumor burden may confer increased risk for severe neurotoxicity.

HBB gene mutations lead to many kinds of diseases, of which, except for the two most common diseases of thalassemia and sickle cell anemia, rare kinds of hemolytic anemia, such as hemoglobin Bristol-Alesha, are rarely reported, no ideal treatment in clinic. A child suffered from chronic recurrent hemolytic attacks and the related genes of hereditary hemolytic anemia were detected on her. Hematopoietic stem cell transplantation was conducted in the treatment of the patient. The patient was diagnosed as hemoglobin Bristol-Alesha and achieved complete recovery after hematopoietic stem cell transplantation. For Bristol-Alesha, without characteristic clinical manifestation and specific biochemical examination, diagnosis is dependent on the gene mutation detection and hematopoietic stem cell transplantation is an effective and curable method.

Zellweger spectrum disorder (ZSD) is a heterogeneous group of autosomal recessive disorders characterized by a defect in peroxisome formation and attributable to mutations in the PEX gene family. Patients with ZSD have profound neurologic impairments, including seizures, severe retardation, and dysmorphic features, and poor prognosis. Currently, there is no specific, effective treatment. Here, we investigated the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on PEX1-related ZSD. The suspected clinical proband was first diagnosed at the Department of Neurology of our hospital. The proband died soon after diagnosis, and his family was studied. We found that a brother had the same genetic alterations, and he was diagnosed with Infantile Refsum disease (IRD) as the mildest form of ZSD. We implemented treatment with allo-HSCT, at the request of the child's parents. After transplantation, we observed significant improvements in the clinical manifestations, very-long-chain fatty acids, and brain MRI. The patient has recovered well and not showed any abnormal clinical manifestations after 2 years of follow-up. We have achieved satisfactory short-term results in the treatment of ZSD-IRD with allo-HSCT. Long-term follow-up and observation will be performed to determine the long-term prognosis.

Dual infection with two pathogens can be found in few cases of encephalitis. Cases of sequential infection with EBV and cryptococcal encephalitis in post-transplant patients are rare. We describe a 5-year-old boy with X-linked adrenoleukodystrophy who presented sequential infection with EBV and cryptococcal encephalitis after umbilical cord blood transplant. The patient showed fever, vomiting and emotional agitation with EBV DNA detected in CSF on day 100. The child underwent 3 doses of intravenous rituximab with a good response. However, the child presented with right facial paralysis, headache, and fever on day 130 after 2 weeks of clinical stability. Brain MRI demonstrated chronic granuloma formed with ring enhancement. FilmArray ME PCR confirmed the existence of Cryptococcus neoformans/gattii in the CSF. The child underwent sequential treatment with amphotericin liposome B and flucytosine. Maintenance treatment with fluconazole was administered for 1 year. Facial paralysis was on longer present on day 260. Cryptococcus neoformans/gattii was not detected on day 310. The biochemistry and cell count of the CSF were completely normal on day 520. Follow-up 2.5 years after presentation, brain MRI changes showed near complete resolution of the lesions. The child survived for 3 years to the last following-up. Invasive cryptococcal encephalitis is rare and life-threatening complication of transplantation. It is important to recognize dual infections, and perform treatment quickly to improve the prognosis of encephalitis after transplantation.

建立了多元件谐振腔本征模的有限元传输矩阵模型.提出了模式计算相对误差概念及相应表达式,该表达式在数值上不受菲涅耳数的影响,能够很好反映有限单元划分方案对不同菲涅耳数的谐振腔的模式计算精度的影响.提出了有限单元划分精细度的概念和相应表达式,用以表征有限单元划分的精细程度.该表达式以菲涅耳数作为有限元传输矩阵法对腔镜单元格数划分的相对要求,用镜面实际划分的单元格数与菲涅耳数的比值来表征有限单元划分的精细程度.分析了不同谐振腔参数变化时模式计算相对误差与有限单元划分精细度的关系,建立了3种不同函数形式的经验表达式,并通过比较拟合残差选择了拟合效果较好的表达式.