Prognostic factors for intermediate- or high-risk neuroblastomas in children in China.

BACKGROUND: Evidence regarding the characteristics and prognosis of neuroblastoma (NBL) in China is limited. We aimed to investigate the characteristics and prognosis of intermediate- or high-risk NBL in children in China. METHODS: We included 147 patients with intermediate- or high-risk NBL evaluated from January 2006 to March 2015. The patients were aged 1 month to 15.5 years, 66% of them were boys, and 117 (79.6%) were diagnosed with high-risk NBL. RESULTS: After a median follow-up of 32.5 months, 80 (45.6%) patients survived, with a median survival time of 48 months (95% confidence interval [CI]: 36.41-59.59). High-risk patients (hazard ratio [HR]: 12.467; 95% CI: 11.029-12.951), partial response (PR) (HR: 1.200; 95% CI: 1.475-2.509) or progression disease (PD) (HR: 1.924; 95% CI: 1.623-3.012) after induction chemotherapy, and intracranial metastasis (HR: 3.057; 95% CI: 0.941-4.892) were independent risk factors for survival (p < 0.05) and postrelapse survival (p < 0.05). NBL relapse, male sex, and PR or PD after induction chemotherapy were risk factors for event-free survival (p < 0.05). CONCLUSIONS: In addition to previously established independent risk factors, such as age, risk group, and relapse, efficacy of induction chemotherapy and intracranial metastasis play significant roles in the prognosis of NBL.

Clinical analysis of 2790 children with retinoblastoma: a single-center experience in China.

BACKGROUND: In this study, we aimed to analyze the clinical characteristics and prognosis of children with retinoblastoma (RB) in a single center in China with a large sample collection spanning 17 years. METHODS: The clinical data of 2790 children with RB treated in Beijing Tongren Hospital from 2005 to 2021 were collected, and a retrospective analysis was conducted. RESULTS: The median age of the participants was 28.3 months. There were 3624 affected eyes, 12.4% of which were in groups A-C, 67.1% in groups D-E and 16.2% were not specified. The primary symptom observed in most cases was a white pupil, accounting for 66.5%, followed by strabismus (12.8%). The median follow-up time was 59.7 months. The enucleation rate was 71.3% (703/986) in a single left eye and 72.5% (702/968) in a single right eye. The overall survival (OS) rate was 95.8% (2444/2552) because 237 patients dropped out, and 109 died. Kaplan‒Meier survival analysis showed that the median survival time (MST) was 125.92 months [95% confidence interval (CI) = 124.83-127.01]. Cox multivariate survival analysis showed that trilateral RB (P = 0.017), metastasis site (P = 0.001), and combined distant tissue metastasis (P = 0.001) were independent prognostic factors for RB. The OS of 44 cases of familial RB was 93.2% (41/44), with an MST of 80.62 months (95% CI = 67.70-93.54). CONCLUSIONS: The timing of eye protection treatment and enucleation should be comprehensively judged to avoid worsening prognosis due to operation time delay. More importantly, the promotion and popularization of diagnosis and treatment technologies are necessary to further improve RB prognosis.

Prognostic factors in children with head and neck rhabdomyosarcoma: A 12-year retrospective study.

INTRODUCTION: To identify possible prognostic factors in children with head and neck rhabdomyosarcoma (RMS). METHODS: A total of 98 patients with head and neck RMS were enrolled in this retrospective study from February 2005 to September 2017. Prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. Survival curves were calculated by Kaplan-Meier method. RESULTS: At the study closing date, there were 60 patients alive, 37 patients died, one patient was lost to follow-up, and 47 patients relapsed. The median disease-specific survival was 60.00 ± 25.36 months, and the overall survival (OS) rate was 61.9%. Complete remission was associated with a longer disease-specific survival (86.6%) compared with partial remission (6.7%). In addition, patients with age >3 years had better OS rate (69.0%) compared with age ≤3 years (42.3%). Univariate and multivariate analysis showed that chemotherapy efficacy and age were prognostic factors of disease-specific survival. CONCLUSIONS: Improvement in outcome was obtained with comprehensive treatment for head and neck RMS. Both chemotherapy efficacy and age of patients were prognostic factors for children with head and neck RMS, which provide some valuable information for further treatment.

[Prognostic Significance of Joint Detection of miR-210 and Minimal Residual Disease in Pediatric Acute Lymphoblastic Leukemia].

OBJECTIVE: To detect the expression of microRNA-210(miR-210) in childhood acute lymphoblastic leukemia(ALL), and to evaluate the role of the joint detection of miR-210 and MRD in the prognosis and clinical treatment of pediatric ALL. METHODS: Eighty-eight children diagnosed with ALL were included in the study. miR-210 was quantitatively detected by real-time quantitative polymerase chain reaction(RQ-PCR) in 88 ALL patients. The average Ct value of samples obtained from 5 pediatric ALL patients with long-term complete continuous remission (CCR>5 years) was used as a calibrator. The expression levels of miR-210 in newly diagnosed patients was calculated by the 2-ΔΔCt method and presented as multiple changes compared with that of the 5 CCR patients. RESULTS: The expression of miR-210 in the favorable prognosis group was significantly higher than that in the unfavorable prognosis group (10.64±1.5 vs 3.27±0.68)(P<0.05). Compared with the miR-210 high-expression group, poorer relapse-free survival(RFS), event-free survival(EFS) and overall survival(OS) (P all <0.001) were found in the low-expression group. Based on the expression of miR-210 and MRD, the 88 cases were divided into 3 groups. The relapse rate of miR-210-MRD high-risk group (70%) was significantly higher than that of the miR-210-MRD middle-risk group(6.25%) and miR-210-MRD low-risk group (2.1%). Kaplan-Meier survival analysis demonstrated that the miR-210-MRD high-risk group had poorer RFS, EFS and OS than those in other 2 groups (P all <0.01). CONCLUSION: The expression level of miR-210 is an independent prognostic factor for pediatric ALL, and the miR-210 is a good useful indicator for predicting the relapse and induction failure of childhood ALL. Joint detection of miR-210 and MRD can help predict outcomes more precisely, thus may be used as an effective mean of determining prognosis, monitoring recurrence, and guiding treatment.

[Clinical features and outcomes of neuroblastoma patients aged above 5 years].

OBJECTIVE: To investigate the clinical features and outcomes of neuroblastoma (NB) children aged above 5 years, and to provide a theoretical basis for improving prognosis. METHODS: A retrospective analysis was performed for the clinical data of 54 previously untreated NB children, and their clinical features and outcome were analyzed. The Kaplan-Meier method was used for survival analysis. RESULTS: Among the 54 children, there were 36 boys and 18 girls, and all of them had stage 3 or 4 NB. Of all the children, 41 (41/54, 76%) had retroperitoneal space-occupying lesions, 10 (10/54, 18%) had mediastinal space-occupying lesions, 2 (2/54, 4%) had intraspinal space-occupying lesions, and 1 (1/54, 2%) had pelvic space-occupying lesions. At the end of the follow-up, 30 children (30/54, 56%) survived, among whom 23 (77%) achieved disease-free survival (9 achieved complete remission after chemotherapy for recurrence), 6 (20%) achieved partial remission of tumor (all of them received chemotherapy again due to recurrence), and 1 (3%) experienced progression (with progression after chemotherapy again due to recurrence); 24 children (44%) died, among whom 22 died after chemotherapy again due to recurrence and 2 died of multiple organ failure during the first treatment. According to the Kaplan-Meier survival analysis, the mean survival time was 53.8 months, and the children with stage 3 NB had a significantly higher overall survival rate than those with stage 4 NB (80% vs 53%; p<0.01). The children with recurrence had a significantly lower mean survival time than those without recurrence (51.68 months vs 62.57 months; p<0.01). CONCLUSIONS: Older children often have late-stage NB, but standard treatment can improve their outcomes.

[Comparison of the efficacy of two chemotherapy protocols for children with TEL-AML1[STBZ] fusion gene positive acute lymphoblastic leukemia].

This study was aimed to compare the curative effect of BCH - 2003 protocol and CCLG - 2008 protocol for children with TEL-AML1 fusion gene positive childhood acute lymphoblastic leukemia (ALL) and to investigate the more suitable protocol for this subtype of childhood leukemia. The clinical data for children with TEL-AML1 fusion gene positive ALL admitted from January 2003 to October 2010 in Hematology Center of Beijing Children's Hospital were collected. The common clinical characteristics including prednisone response at day 8, minimal residual disease (MRD) at the end of induction of remission (day 33), event free survival (EFS), relapse free survival (RFS) were compared. The results showed that out of 204 children with TEL-AML1 fusion gene positive ALL, 134 and 70 patients were treated by BCH-2003 protocol and CCLG-2008 protocol respectively. There were no statistical difference in age, white blood cell count in peripheral blood at presentation, prednisone response and CNS involvement. However, there were more boys in CCLG-2008 group (P = 0.025). The negative rate of MRD at day 33 in BCH-2003 group was lower than that in CCLG-2008 group (P = 0.013). After re-stratifying the patients in CCLG-2008 group according to the stratification criteria of BCH-2003 protocol, the negative rate of MRD at day 33 of patients with intermediate risk remained higher in BCH-2003 group than that in CCLG-2008 group (P = 0.014) . However, no significant difference in the patients with standard risk was found. There were also no significant statistical differences in the incidence of severe infection, EFS and RFS, (P = 1.000, P = 0.327,P = 0.251 respectively) during chemotherapy. It is concluded that for children with TEL-AML1 fusion gene positive ALL, the induction of remission of BCH - 2003 protocol can decrease leukemic load more quickly than that of CCLG - 2008 protocol. However, the outcome of the patients treated by the two protocols is similar.

E2F3a gene expression has prognostic significance in childhood acute lymphoblastic leukemia.

OBJECTIVES: To study E2F3a expression and its clinical significance in children with acute lymphoblastic leukemia (ALL). METHODS: We quantified E2F3a expression at diagnosis in 148 children with ALL by real-time PCR. In the test cohort (n = 48), receiver operating characteristic (ROC) curve was used to find the best cut-off point to divide the patients into E2F3a low- and high-expression groups. The prognostic significance of E2F3a expression was investigated in the test cohort and confirmed in the validation cohort (n = 100). The correlations of E2F3a expression with the clinical features and treatment outcome of these patients were analyzed. RESULTS: ROC curve analysis indicated that the best cut-off point of E2F3a expression was 0.3780. In the test cohort, leukemia-free survival (LFS) and event-free survival (EFS) of the low-expression group were lower than those of the high-expression group (log rank: P = 0.026 for both). This finding was verified in the validation cohort. LFS, EFS, and overall survival were also lower in the low-expression group than in the high-expression group (log rank, P = 0.015, 0.008, and 0.002 respectively). E2F3a low expression was correlated with the existence of BCR-ABL fusion. An algorithm composed of E2F3a expression and minimal residual disease (MRD) could predict relapse or induction failure more precisely than current risk stratification. These results were still significant in the ALL patients without BCR-ABL fusion. CONCLUSIONS: Low expression of E2F3a was associated with inferior prognosis in childhood ALL. An algorithm composed of E2F3a expression and MRD could predict relapse or induction failure more precisely than that of the current risk stratification.

[Evaluation of the efficacy of two successive protocols on pediatric acute lymphoblastic leukemia with E2A-PBX1 fusion gene].

OBJECTIVE: To evaluate the efficacy of BCH-03 and CCLG-08 protocols in treating E2A-PBX1 pediatric acute lymphoblastic leukemia (ALL). METHOD: From January 2003 to January 2011, 59 ALL patients identified as E2A-PBX1 were analyzed in a retrospective study. There were 37 and 22 patients treated with Protocol BCH-03 and CCLG-08, respectively. The clinical characteristics at diagnosis, response to early treatment, the time of relapse, relapse-free survival (RFS) and event-free survival (EFS) in the two groups were analyzed. RESULT: There were no significant differences in gender, age, initial white blood cell count, the central nervous system involvement, immunophenotype, prednisone response, the rate of complete remission, and the time of relapse between the two groups (P > 0.05). The only difference in induction therapy of the two protocols existed in the glucocorticoids used, that is, BCH-03 used 60 mg/m(2) prednisolone and CCLG-08 used 6 mg/m(2) dexamethasone. The doses of vincristine, daunorubicin and L-asparaginase were the same in the two groups. At the end of induction therapy, the MRD negativity rate in BCH-03 group was significantly higher than that in CCLG-08 group (84.2% vs. 47.1%, P = 0.018). The incidences of severe infection of the two groups during induction of remission were similar (P = 0.135). The EFS of BCH-03 group was significantly superior to that of CCLG-08 group (94.5% vs. 71.5%, P = 0.010), and the RFS of BCH-03 group tended to be better than that of CCLG-08 group (94.5% vs. 78.6%, P = 0.059). CONCLUSION: Compared to Protocol CCLG-08, Protocol BCH-03 was more effective for pediatric E2A-PBX1 ALL, and 60 mg/m(2) prednisolone was more suitable for the induction therapy of this subtype of pediatric ALL.

[Suppression of NAMPT expression enhances the sensitivity of K562 cells to imatinib and its relative mechanism].

The aim of this study was to investigate the effect of suppression of nicotinamide phosphoribosyltransferase (NAMPT) expression on imatinib-sensitivity in chronic myelogenous leukemia (CML) cell line K562 and its mechanisms, NAMPT siRNA was synthesized and transfected into K562 cells. PI/Calcein staining technique was used to determine survival rate of transfected K562 cells at 48th hour after exposure to 1 µmol/L imatinib. MTS method was used to determine the proliferation changes of transfected K562 cell at 48th hour after exposure to different doses of imatinib, then half inhibitory concentration (IC(50)) was calculated. Expression of NAMPT at 3rd-48th hour after exposure to 1 µmol/L imatinib was determined by Western blot. To explore the effect of NAMPT-siRNA and imatinib on the expression of apoptosis-related genes, the microarray data from NCBI GEO Data-Sets was analyzed, then the results were confirmed by Western blot. The luciferase reporter assay was used to determine the effect of NAMPT and imatinib on transcriptional activity of NF-κB transcription factors. The results showed that after exposure to 1 µmol/L imatinib for 3 - 48 h, there was no significant change of NAMPT expression in K562 cells. The expression of NAMPT could be effectively inhibited by the NAMPT-siRNA. After exposure to 1 µmol/L of imatinib for 48 h, the survival rate of NAMPT-siRNA interference group was lower than that of negative control group (P < 0.05), indicating that suppression of NAMPT expression can increase the sensitivity of K562 cells to imatinib and enhance the killing effect of imatinib on K562 cells. The IC(50) of imatinib in NAMPT-siRNA interference group was the lowest compared with that of control group (P < 0.05) after exposure to different concentrations of imatinib for 48 h, the fitted survival curves showed that the slope of NAMPT-siRNA interference group was the largest ranging between 0.01 - 0.1 µmol/L of imatinib. Data mining of expression profiling indicated that the anti-apoptotic factor Bcl-2 decreased in K562 cells treated with either NAMPT-siRNA or imatinib, which was confirmed by Western blot. The inhibitory effect was much more significant when both NAMPT-siRNA and imatinib were used. The results of luciferase reporter assay showed that either NAMPT-siRNA or imatinib decreased transcriptional activity of NF-κB. The decreased effect was much more significant when both NAMPT-siRNA and imatinib were used. It is concluded that survival of K562 cells affected by imatinib may not be due to regulation of expression of NAMPT. When expression of NAMPT decreases, the K562 cells are more sensitive to imatinib, this may be related with the decreased transcriptional activity of NF-κB and its downstream effector Bcl-2.