[Analysis of clinical presentation and genetic characteristics of malignant infantile osteopetrosis].

Objective: To investigate the clinical presentation and genetic characteristics of malignant infantile osteopetrosis. Methods: This was a retrospective case study. Thirty-seven children with malignant infantile osteopetrosis admitted into Beijing Children's Hospital from January 2013 to September 2022 were enrolled in this study. According to the gene mutations, the patients were divided into the CLCN7 group and the TCIRG1 group. Clinical characteristics, laboratory tests, and prognosis were compared between two groups. Wilcoxon test or Fisher exact test were used in inter-group comparison. The survival rate was estimated with the Kaplan-Meier method and the Log-Rank test was used to compare the difference in survival between groups. Results: Among the 37 cases, there were 22 males and 15 females. The age of diagnosis was 0.5 (0.2, 1.0) year. There were 13 patients (35%) and 24 patients (65%) with mutations in CLCN7 and TCIRGI gene respectively. Patients in the CLCN7 group had an older age of diagnosis than those in the TCIRGI group (1.2 (0.4, 3.6) vs. 0.4 (0.2, 0.6) years, Z=-2.60, P=0.008). The levels of serum phosphorus (1.7 (1.3, 1.8) vs. 1.1 (0.8, 1.6) mmol/L, Z=-2.59, P=0.010), creatine kinase isoenzyme (CK-MB) (457 (143, 610) vs. 56 (37, 82) U/L, Z=-3.38, P=0.001) and the level of neutrophils (14.0 (9.9, 18.1) vs. 9.2 (6.7, 11.1) ×109/L, Z=-2.07, P=0.039) at diagnosis were higher in the CLCN7 group than that in the TCIRG1 group. However, the level of D-dimer in the CLCN7 group was lower than that in the TCIRGI group (2.7 (1.0, 3.1) vs. 6.3 (2.5, 9.7) µg/L, Z=2.83, P=0.005). After hematopoietic stem cell transplantation, there was no significant difference in 5-year overall survival rate between the two groups (92.3%±7.4% vs. 83.3%±7.6%, χ²=0.56, P=0.456). Conclusions: TCIRGI gene mutations are more common in children with osteopetrosis. Children with TCIRGI gene mutations have younger age, lower levels of phosphorus, CK-MB, and neutrophils and higher level of D-dimer at the onset. After hematopoietic stem cell transplantation, patients with CLCN7 or TCIRGI gene mutations have similar prognosis.

[Clinical characteristics and prognostic analysis of 458 children with high-risk neuroblastoma in a single center].

Objective: To summarize the clinical characteristics of high-risk neuroblastoma (HR-NB) in a single center, analyze the prognostic factors of HR-NB. Methods: The clinical data of children with HR-NB who were treated and followed up at the hematology-oncology center of Beijing Children's Hospital from February 1, 2007 to June 30, 2018 were analyzed retrospectively. The clinical features were summarized. Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. The last follow-up time was June 30, 2019. Results: A total of 458 children with HR-NB were enrolled in this study, including 265 males (57.9%) and 193 females (42.1%), the age at diagnosis was 40.0 months (4.5-148.0 months), the follow-up time was 22.0 months (0.2-138.0 months) and the time of tumor progression or recurrence was 15 months (1-72 months). The 5-year event-free survival (EFS) rate was (31.2±2.6)% and the 5-year overall survival (OS) rate was (43.9±3.2)%. The 5-year EFS rate and 5-year OS rate in 142 hematopoietic stem cell transplantation (HSCT) patients with bone marrow metastases were better than that in 196 non-transplantation cases with bone marrow metastases ((26.5±4.5)% vs. (25.1±3.6)%, χ²=13.773, P=0.001; (38.1±5.5)% vs. (35.7±4.7)%, χ²=9.235, P=0.002); 128 transplantation patients with bone metastases had higher 5-year EFS rate and 5-year OS rate than 188 non-transplantation cases with bone metastases ((28.5±5.0)% vs. (26.7±3.8)%, χ²=10.222, P=0.001; (37.1±6.0)% vs. (36.2±4.8)%, χ²=7.843, P=0.005). The 5-year EFS rate was higher in 37 HSCT patients with MYCN amplification than in 49 non-transplantation cases with MYCN amplification ((26.8±8.0) % vs. (20.5±6.4) %, χ²=5.732, P=0.017). No significant difference was found in 5-years OS rate between transplantation group with MYCN amplification and non-transplantation group with MYCN amplification ((31.4±8.6) % vs. (26.2±7.4) %, χ²=3.230, P=0.072). Univariate survival analysis showed that lactate dehydrogenase (LDH)≥1 500 U/L was associated with poor prognosis of patients with MYCN amplification (χ²=6.960, P=0.008). Multivariate Cox analysis showed bone marrow metastasis and LDH≥1 500 U/L were independent risk factors for poor prognosis of patients with non-MYCN amplification (HR=2.427, 1.618;95%CI：1.427-4.126, 1.275-2.054, P<0.05) for both comparisons. Conclusions: LDH≥1 500 U/L was the poor prognostic factor for patients with MYCN amplification. The bone marrow metastasis and LDH≥1 500 U/L were the poor prognostic factors for HR-NB patients with non-MYCN amplification. HSCT can improve the prognosis of patients with bone or bone marrow metastasis. It can also retard the time of progression or recurrence for patients with MYCN amplification.

G-CSF Indirectly Induces Apoptosis of Osteoblasts During Hematopoietic Stem Cell Mobilization.

The objective of this study was to explore the mechanism underlying osteoblast suppression in the process of hematopoietic stem cells mobilization induced by granulocyte colony-stimulating factor (G-CSF). The apoptosis of human and mouse osteoblasts was examined by detecting caspase 3. The levels of serum DKK1 and osteocalcin in the supernatant of co-culture of mouse osteoblasts and mouse bone marrow nucleated cells were measured. The number of mouse osteoblasts co-cultured with mouse bone marrow nucleated cells was measured and the osteocalcin mRNA level was also measured. The G-CSF-induced decrease in osteoblast function was partly due to the apoptosis of osteoblasts. There was no significant difference in the level of serum DKK1 in healthy donors before and 5 days after mobilization. The osteocalcin gene and protein expression was significantly different in co-cultured osteoblasts with bone marrow nucleated cells treated with and without G-CSF. Osteoblasts undergo apoptosis during mobilization and G-CSF affects osteoblasts through bone marrow nucleated cells.