Survival analysis of children with stage II testicular malignant germ cell tumors treated with surgery or surgery combined with adjuvant chemotherapy / 癌症

For children with stage II testicular malignant germ cell tumors (MGCT), the survival is good with surgery and adjuvant chemotherapy. However, there is limited data on surgical results for cases in which there was no imaging or pathologic evidence of residual tumor, but in which serum tumor markers either increased or failed to normalize after an appropriate period of half-life time post-surgery. To determine the use of chemotherapy for children with stage II germ cell tumors, we analyzed the outcomes (relapse rate and overall survival) of patients who were treated at the Sun Yat-sen University Cancer Center between January 1990 and May 2013. Twenty-four pediatric patients with a median age of 20 months (range, 4 months to 17 years) were enrolled in this study. In 20 cases (83.3%), the tumors had yolk sac histology. For definitive treatment, 21 patients underwent surgery alone, and 3 patients received surgery and adjuvant chemotherapy. No relapse was observed in the 3 patients who received adjuvant chemotherapy, whereas relapse occurred in 16 of the 21 patients (76.2%) treated with surgery alone. There were a total of 2 deaths. Treatment was stopped for 1 patient, who died 3 months later due to the tumor. The other patient achieved complete response after salvage treatment, but developed lung and pelvic metastases 7 months later and died of the tumor after stopping treatment. For children treated with surgery alone and surgery combined with adjuvant chemotherapy, the 3-year event-free survival rates were 23.8% and 100%, respectively (P = 0.042), and the 3-year overall survival rates were 90.5% and 100%, respectively (P = 0.588). These results suggest that adjuvant chemotherapy can help to reduce the recurrence rate and increase the survival rate for patients with stage II germ cell tumors.

Brain metastasis in children with stage 4 neuroblastoma after multidisciplinary treatment / 癌症

<p><b>INTRODUCTION</b>Brain metastasis is common in relapsed neuroblastoma patients, but the characteristics of brain metastasis remain largely unknown. This study aimed to investigate the status of brain metastasis with neuroblastoma in South China.</p><p><b>METHODS</b>In this retrospective case-based study, 106 patients with stage 4 neuroblastoma from the Department of Pediatric Oncology in Sun Yat-sen University Cancer Center between January 2004 and May 2013 were included. The incidence, risk factors, and survival status of these patients were reviewed and analyzed.</p><p><b>RESULTS</b>Of the 106 patients, 11 (10.4%) developed brain metastasis, accounting for 20.0% of 55 patients with relapse or progression. The age at initial diagnosis of the 11 patients ranged from 2 to 10 years (median 4 years), which was younger than that of the patients without brain metastasis (median 5 years, range 1-10 years, P=0.073). The male to female ratio of the 11 patients was 8:3, which was not significantly different from that of the patients without brain metastasis (P=0.86). Patients with brain metastasis had higher lactate dehydrogenase levels than those without brain metastasis, but the differences were not significant (P=0.076). Eight patients died, and 3 patients survived. The median interval from the initial diagnosis to the development of brain metastasis was 18 months (range 6-32 months). The median survival was 4 months (range 1 day to 29 months) after the diagnosis of brain metastasis. The median interval from the manifestation of brain metastasis to death was 3 months (range 1 day to 11 months).</p><p><b>CONCLUSIONS</b>High-risk factors for brain metastasis in cases of neuroblastoma include bone marrow involvement and a younger age at initial diagnosis. Nevertheless, multiple treatment modalities can improve disease-free survival.</p>

The clinical characteristics and treatment outcome of 57 children and adolescents with primary central nervous system germ cell tumors / 癌症

Primary central nervous system germ cell tumors (CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years (range, 2.7 to 18.0 years) at diagnosis; 43 (75.4%) had non-germinomatous germ cell tumors (NGGCTs) and 14 (24.6%) had germinomas; 44 (77.2%) had localized disease and 13 (22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB (cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months (range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival (EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs (P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively (P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.

Outcome of children and adolescents with Burkitt lymphoma and diffuse large B cell lymphoma treated with a modified NHL-BFM-90 protocol / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of a modified NHL-BFM-90 protocol in childhood and adolescence with Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>A total of 138 de novo patients with BL and DLBCL were enrolled. All patients were stratified into low (R1), intermediate (R2) and high risk (R3) groups based on the stage, chemotherapy response and LDH level, and treated with a modified NHL-BFM 90 protocol.</p><p><b>RESULTS</b>Of the 138 patients, 105 were boys and 33 girls, with a median age at diagnosis of 7.5 yr (range 1.5 to 20.0 yr). Eighty-two cases were BL, 56 cases DLBCL. The patients with stage III/IV accounted for 76.1%. Thirty-one patients were assigned to group R1, 38 patients group R2, and 69 patients group R3. Complete remission (CR) after chemotherapy was 90.6%. At a median follow-up of 50 months(1-158 months), a total of 19 patients died of disease. The 5-year event free survival (EFS) and overall survival (OS) for the entire group were 85.8%, 85.8% respectively. 5-year EFS was 97.1% for stage I/II, 82.1% for stage III/IV respectively (P=0.039); and 96.7%, 86.8% and 80.2% for groups R1, R2 and R3 respectively (P=0.135); and 85.2% and 86.9% for BL and DLBCL respectively (P=0.635). Major toxicity was myelosuppression, which was tolerant and manageable.</p><p><b>CONCLUSION</b>That the modified NHL-BFM-90 protocol was highly effective for children and adolescents with BL and DLBCL, and especially improved the survival of the advanced patients.</p>

Germinal-center type B-cell classification and clinical characteristics of Chinese pediatric diffuse large B-cell lymphoma: a report of 76 cases / 癌症

Pediatric diffuse large B-cell lymphoma (DLBCL) is a highly aggressive disease with unique clinical characteristics. This study analyzed the germinal-center type B-cell (GCB) classification and clinical characteristics of Chinese pediatric DLBCL. A total of 76 patients with DLBCL newly diagnosed in Sun Yat-sen University Cancer Center between February 2000 and May 2011, with an age younger than 18 years, were included in the analysis. The male/female ratio was 3.47:1. The median age was 12 years (range, 2 to 18 years), and 47 (61.8%) patients were at least 10 years old. Of the 76 patients, 48 (63.2%) had stage III/IV disease, 9 (11.8%) had bone marrow involvement, 1 (1.3%) had central nervous system (CNS) involvement, and 5 (6.6%) had bone involvement. The GCB classification was assessed in 45 patients: 26 (57.8%) were classified as GCB subtype, and 19 (42.2%) were classified as non-GCB subtype. The modified B-NHL-BFM-90/95 regimen was administered to 50 patients, and the 4-year event-free survival (EFS) rate was 85.8%. Among these 50 patients, 31 were assessed for the GCB classification: 17 (54.8%) were classified as GCB subtype, with a 4-year EFS rate of 88.2%; 14 (45.2%) were classified as non-GCB subtype, with a 4-year EFS rate of 92.9%. Our data indicate that bone marrow involvement and stage III/IV disease are common in Chinese pediatric DLBCL patients, whereas the percentage of patients with the GCB subtype is similar to that of patients with the non-GCB subtype. The modified B-NHL-BFM-90/95 protocol is an active and effective treatment protocol for Chinese pediatric patients with DLBCL.

Safety of in vitro amplified HLA-haploidentical donor immune cell infusions for childhood malignancies / 癌症

In vitro amplified human leukocyte antigen (HLA)-haploidentical donor immune cell infusion (HDICI) is not commonly used in children. Therefore, our study sought to evaluate its safety for treating childhood malignancies. Between September 2011 and September 2012, 12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center. The median patient age was 5.1 years (range, 1.7-8.4 years). Of the 12 patients, 9 had high-risk neuroblastoma (NB) [7 showed complete response (CR), 1 showed partial response (PR), and 1 had progressive disease (PD) after multi-modal therapies], and 3 had Epstein-Barr virus (EBV)-positive lymphoproliferative disease (EBV-LPD). The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×10(8) immune cells/kg body weight: 71 infusions with natural killer (NK) cells, 8 with cytokine-induced killer (CIK) cells, and 13 with cascade primed immune cells (CAPRIs); 83 infusions with immune cells from the mothers, whereas 9 with cells from the fathers. Twenty cases (21.7%) of fever, including 6 cases (6.5%) accompanied with chills and 1 (1.1%) with febrile convulsion, occurred during infusions and were alleviated after symptomatic treatments. Five cases (5.4%) of mild emotion changes were reported. No other adverse events occurred during and after the completion of HDIDIs. Neither acute nor chronic graft versus host disease (GVHD) was observed following HDICIs. After a median of 5.0 months (range, 1.0-11.5 months) of follow-up, the 2 NB patients with PR and PD developed PD during HDICIs. Of the other 7 NB patients in CR, 2 relapsed in the sixth month of HDICIs, and 5 maintained CR with disease-free survival (DFS) ranging from 4.5 to 11.5 months (median, 7.2 months). One EBV-LPD patient achieved PR, whereas 2 had stable disease (SD). Our results show that HDICI is a safe immunotherapy for childhood malignancies, thus warranting further studies.

Analysis of PTPN11 mutation in children leukemia and its clinical significance / 中国实验血液学杂志

This study was aimed to explore the frequency of PTPN11 mutation in children with leukemia and its clinical significance. Genomic DNAs were extracted from peripheral leukocytes of 131 patients with leukemia, including 101 cases of ALL, 26 cases of AML, 3 cases of CML and 1 case of juvenil myelomonocytic leukemia (JMML). The sequences of PTPN11 exons 3, 8, 13 were amplified by polymerase chain reaction (PCR), and the clinical characteristics of positive patients were analyzed. The results indicated that the PTPN11 mutation was found in 10 cases (9.9%) from newly diagnosed 101 cases of ALL. Grouping the newly diagnosed ALL children by various clinical features, it was found that the PTPN11 mutation did not show associations with sex, age, white blood cell (WBC) count, prednisone test sensitivity, clinical risk and disease recurrences at the first visit (P > 0.05). PTPN11 mutations were found in 2 cases out of 26 AML patients, including one AML-M(2) and one AML-M(4). No PTPN11 mutation in 3 CML patients was found. Exon 13 mutation of PTPN11 gene was found in 1 case of JMML. It is concluded that the E76 of exon 3 is the hot spot of PTPN11 mutation in children leukemia. The novel G503E (1508G > A) mutation is detected in one JMML patient. The PTPN11 mutation does not associate with the sex, age, WBC count, prednisone sensitive test and early recurrence.

Relationship between polymorphism of HLA-A, -B, -DRB1 alleles and susceptibility of children to acquired aplastic anemia / 中国实验血液学杂志

The aim of this study was to identify the relationship between susceptibility of children to acquired aplastic anemia (AA) and HLA-A, -B, -DRB1 alleles. 80 children with AA were enrolled in this study. Among of them, 34 patients collected from tissue typing test centers of Nanfang Hospital; 46 patients were diagnosed at Department of Pediatrics of Sun Yat-Sen Memorial Hospital. In these patients, 48 were males, 32 were females, and with average age 8.1 years old, 6 cases were non-severe AA (nSAA), 74 case were severe AA (SAA). The healthy control group consisted of 109 donors who were from the same area. All the patients and healthy controls were of Han Chinese, and all were unrelated individuals. The polymerase chain reaction sequence specific primers (PCR-SSP) was used to analyze the polymorphism of HLA-A, -B and -DRB1 alleles. Pearson Chi-square or continuity correction or two-sided Fisher's exact test were used. The results showed that the genotype frequency of HLA-B*48:01 and DRB1*09:01 were significantly higher in children with AA as compared with healthy controls (P < 0.05). The genotype frequency of HLA-B*51:01, DRB1*03:01 and DRB1*11:01 were significantly lower in children with AA as compared with healthy controls (P < 0.05). Besides, the results also demonstrated that the genotype frequencies of HLA-B*48:01 and DRB1*09:01 were significantly higher in SAA as compared with controls, the genotype frequencies of B*51:01, DRB1*03:01 and DRB1*11:01 were significantly lower in SAA, as compared with controls. In conclusion, HLA-B*48:01 and DRB1*09:01 are related with children AA, and may be susceptible alleles to the development of children AA. Besides, the expression of HLA-B*51:01, DRB1*03:01 and DRB1*11:01 are low in children with AA, whether they are relative protection alleles of children needs to be further studied.

Diversity changes of the microbial communities and bla(CTX-M) genes in urban river sediments treated with cefotaxime / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the diversity changes of microbial communities and bla(CTX-M) in an urban river sediment community with cefotaxime treatment.</p><p><b>METHODS</b>The terminal restriction fragment length polymorphism (T-RFLP) of 16S rDNA was employed to analyze the bacteria community, and the bla(CTX-M) was determined using nested PCR. The sediment was treated by cefotaxime at the concentrations of 0, 6.4, 64, and 320 mg/L.</p><p><b>RESULTS</b>According to statistical analysis of the T-RFs, no significant correlation was observed between the antibiotic treatment and the microbial community change, but incubation in laboratory conditions had significant effect on the microbial diversity. The PCR results showed that the diversity of bla(CTX-M) decreased after the laboratory incubation.</p><p><b>CONCLUSION</b>As there are diverse antibiotic resistant bacteria in the sediments with prior pollution by antibiotics, the whole community can be inert to the antibiotic treatment. Nevertheless, the ex situ treatment conditions in laboratory studies have a significant impact on the community structures.</p>