[Analysis of 41 cases of non-metastatic Ewing's sarcoma in children]. / 儿童非转移性尤文肉瘤41例分析.

OBJECTIVES: To summarize the clinical characteristics, treatment outcomes, and prognostic factors of children with non-metastatic Ewing's sarcoma (ES). METHODS: A retrospective analysis was conducted on the clinical data of 41 children with non-metastatic ES diagnosed and treated at the Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018. All patients underwent chemotherapy based on the RMS-2009 protocol of the center, and local treatment such as surgery and/or radiotherapy was performed according to risk grouping. The Kaplan-Meier method was used to calculate the overall survival (OS) and event-free survival (EFS) rates. Univariate prognostic analysis was performed using the log-rank test, and multivariate analysis was conducted with Cox regression. RESULTS: Of the 41 children, 21 were male and 20 were female. The median age at diagnosis was 7.7 years (range: 1.2-14.6 years). The median follow-up time for patients with event-free survival was 68.1 months (range: 8.1-151.7 months). As of the last follow-up, 33 patients were in complete remission, and the overall 5-year EFS and OS rates were (78±6)% and (82±6)%, respectively. Univariate analysis by the log-rank test showed that a tumor diameter ≥8 cm, time from diagnosis to start of local treatment ≥16 weeks, and incomplete surgical resection were associated with poor prognosis (P<0.05). Multivariate Cox regression analysis indicated that incomplete surgical resection (HR=8.381, 95%CI: 1.681-41.801, P=0.010) was an independent risk factor for poor prognosis in children with ES. Secondary tumors occurred in 2 cases. CONCLUSIONS: A comprehensive treatment strategy incorporating chemotherapy, surgery, and radiotherapy can improve the prognosis of children with ES. Poor prognosis is associated with an initial tumor diameter ≥8 cm, while complete surgical resection and early initiation of local treatment can improve outcomes.

A prospective multicenter study investigating rituximab combined with intensive chemotherapy in newly diagnosed pediatric patients with aggressive mature B cell non-Hodgkin lymphoma (CCCG-BNHL-2015): a report from the Chinese Children's Cancer Group.

The evidence for the safety and efficacy of adding rituximab to intensive chemotherapy in pediatric patients with aggressive mature B cell non-Hodgkin lymphoma/leukemia (B-NHL/B-AL) is not yet robust. In this prospective multi-institutional trial, 419 evaluable patients ≤ 16 years of age with newly diagnosed B-NHL/B-AL were enrolled. Patients were stratified into 4 risk groups according to stage, resection status, and serum lactate dehydrogenase. Patients in group R1 received 3 therapy courses in the treatment order A-B-A. Patients in group R2 received 5 courses A-B-A-B-A. Patients in group R3 received 6 courses A-BB-AA-BB-AA-BB. For patients in group R4, rituximab was added to the chemotherapy backbone for patients in R3 (A-RBB-RAA-RBB-RAA-BB). At a median follow-up of 54 months, the 4-year event-free survival (EFS) for the entire group was 88.3 ± 1.6% (76.0 ± 4.3% in the historical study). The EFS rates according to the intention-to-treat principle were 100%, 98.6 ± 1.2%, 94.2 ± 1.8%, and 73.5 ± 3.7% for patients in treatment groups R1, R2, R3, and R4, respectively (P < 0.001). There were 9 (2.1%) toxic deaths due to infection during treatment. Regarding the toxicities of rituximab, grade 3/4 thrombocytopenia, mucositis, and infection occurred in 44.0%, 33.3%, and 64.0% after courses R-BB and grade 3/4 neutropenia, thrombocytopenia, and infection occurred in 96.3%, 77.8%, and 54.1% after courses RAA. The addition of rituximab to intensive chemotherapy is feasible even in a developing country. EFS was significantly improved when compared with the historical data. clinicals.gov identifier: NCT02405676.

Cytogenetic Characteristics of Childhood Acute Lymphoblastic Leukemia: A Study of 1541 Chinese Patients Newly Diagnosed between 2001 and 2014.

OBJECTIVE: Cytogenetic abnormalities have been proven to be the most valuable parameter for risk stratification of childhood acute lymphoblastic leukemia (ALL). However, studies on the prevalence of cytogenetic abnormalities and their correlation to clinical features in Chinese pediatric patients are limited, especially large-scale studies. METHODS: We collected the cytogenetics and clinical data of 1541 children newly diagnosed with ALL between 2001 and 2014 in four Chinese hospitals, and retrospectively analyzed their clinical features, prognosis and risk factors associated with pediatric ALL. RESULTS: All of these patients had karyotyping results, and some of them were tested for fusion genes by fluorescence in situ hybridization or reverse-transcription polymerase chain reaction. Overall, 930 cases (60.4%) had abnormal cytogenetics in this study, mainly including high hyperdiploidy (HHD, n=276, 17.9%), hypodiploidy (n=74, 4.8%), t(12;21)/TEL-AML1 (n=260, 16.9%), t(1;19)/E2A-PBX1 (n=72, 4.7%), t(9;22)/BCR-ABL (n=64, 4.2%), and t(v;11q23)/MLL rearrangements (n=40, 2.6%). The distribution of each cytogenetic abnormality was correlated with gender, age, white blood cell count at diagnosis, and immunophenotype. In addition, multivariate analysis suggested that t(v;11q23)/MLL rearrangements (OR: 2.317, 95%CI: 1.219-3.748, P=0.008) and t(9;22)/BCR-ABL (OR: 2.519, 95%CI: 1.59-3.992, P<0.001) were independent risk factors for a lower event-free survival (EFS) rate in children with ALL, while HHD (OR: 0.638, 95%CI: 0.455-0.894, P=0.009) and t(12;21)/TEL-AML1 (OR: 0.486, 95%CI: 0.333-0.707, P<0.001) were independent factors of a favorable EFS. CONCLUSION: The cytogenetic characteristics presented in our study resembled other research groups, emphasizing the important role of cytogenetic and molecular genetic classification in ALL, especially in B-ALL.

Toward the Cure of Acute Lymphoblastic Leukemia in Children in China.

This study explored results of therapy of children with acute lymphoblastic leukemia (ALL) in China, recent progress, and challenges. Included are a survey of therapy outcomes of ALL in Chinese children nationwide, comparison of these data with global ALL therapy outcomes, analyses of obstacles to improving outcomes, and suggestions of how progress can be achieved. Therapy outcomes at many Chinese pediatric cancer centers are approaching those of resource-rich countries. However, nationwide outcomes still need improvement. Obstacles include suboptimal clinical trials participation, children without adequate health care funding, human resource shortages, especially physicians expert in pediatric hematology and oncology, and social-economic disparities. We suggest how these obstacles have been and continue to be remedied including expanded access to protocol-based therapy, improved supportive care, health care reforms, recruitment of trained personnel, and international collaborations. China has made substantial progress treating children with ALL. We envision even better outcomes in the near future.

Clinical Characteristics and Treatment Outcomes of Pediatric Patients with Non-Hodgkin Lymphoma in East Asia.

PURPOSE: The presentations and geographic incidence of pediatric non-Hodgkin lymphoma (NHL) differ from those of adults. This study delineated the characteristics and outcomes of pediatric NHL in East Asia. MATERIALS AND METHODS: Medical records of 749 pediatric patients with NHL treated at participating institutions in mainland China, Japan, Korea, and Taiwan from January 2008 to December 2013 were reviewed. Demographic and clinical features, survival outcomes, and putative prognostic factors were analyzed. RESULTS: Five hundred thirty patients (71%) were male. The most common pathologic subtypes were Burkitt lymphoma (BL) (36%). Six hundred seven patients (81%) had advanced diseases at diagnosis. The 5-year overall survival and event-free survival (EFS) rates were 89% and 84%. The 5-year EFS rates of BL, lymphoblastic lymphoma, and diffuse large B-cell lymphoma were 88%, 88%, and 89%, and those of anaplastic large cell lymphoma (ALCL) and peripheral T-cell lymphoma (PTCL) were 71% and 56% (p < 0.001). Central nervous system involvement, high lactate dehydrogenase level (> 250 IU/mL), and advanced disease at diagnosis (≥ stage III) were associated with poor outcomes (p < 0.05). ALCL and PTCL relapsed more frequently than other pathologic subtypes (p < 0.001). CONCLUSION: In East Asia, PTCL was more frequent than in Western countries, and bone marrow involvement did not affect treatment outcome. This international study should motivate future collaborative study on NHL in East Asia.

[Clinical effect of the SCMC APL-2010 regimen in treatment of acute promyelocytic leukemia in children: an analysis of 44 cases].

OBJECTIVE: To study the clinical effect of the SCMC APL-2010 regimen in the treatment of acute promyelocytic leukemia (APL) in children. METHODS: A retrospective analysis was performed for the clinical data of 44 children with APL who received treatment with the SCMC APL-2010 regimen between April 2010 and July 2016. The Kaplan-Meier survival analysis was used to evaluate event-free survival (EFS) rate and overall survival (OS) rate. RESULTS: Of the 44 children with APL, 42 (95%) achieved a complete remission (CR) after one course of treatment and 1 achieved CR after two courses of treatment, with an overall CR rate of 98%. The 9-year EFS and OS rates were 96%±3% and 97.7%±2.2% respectively. As for adverse events, 41 (93%) had infection, 29 (66%) had granulocyte reduction, 12 (27%, 1 died) had differentiation syndrome, 16 (36%) had liver dysfunction, 12 (27%) had adverse gastrointestinal reactions, and 7 (16%) had QT prolongation, 1 (2%) had orchitis, and no secondary neoplasm was observed. CONCLUSIONS: Children with APL receiving the SCMC APL-2010 regimen have a good prognosis and can achieve a long-term survival, while treatment-related infection is commonly seen.

Association of image-defined risk factors, tumor resectability, and prognosis in children with localized neuroblastoma.

BACKGROUND: Although localized neuroblastoma has a good prognosis, some cases have undergone treatment failure or recurrence. Apart from biologic features such as MYCN status, we wondered whether some characteristics of growing tumors are prognostic, such as a well-encapsulated mass without infiltration of vital organs. We analyzed the diagnostic utility of image-defined risk factors (IDRFs) to predict successful treatment and prognosis. The overall goal was to achieve maximum cure rates for patients with localized neuroblastoma through a better understanding of clinical characteristics. METHODS: We retrospectively reviewed the images of patients with localized neuroblastoma who were enrolled between June 1998 and December 2012 at a single institution in Shanghai, China. Unequivocal categorization regarding IDRFs was available in 67 patients. IDRF was assessed at diagnosis and after four cycles of neoadjuvant chemotherapy, on average. The median follow-up period was 84 months (range: 48-132 months) after diagnosis. RESULTS: MRI and CT indicated a total of 177 IDRFs in these 67 patients. Logistic regression analysis revealed a highly significant negative correlation between the numbers of IDRFs and the possibility of complete removal of neuroblastoma. Intraspinal extension of the tumor, compression of the trachea, and encasement of the main artery in localized neuroblastoma were predictors for incomplete tumor resection. According to univariate analysis, ≥ 4 IDRFs and intraspinal extension of the tumor were significant indicators of poor prognosis. CONCLUSIONS: The number of IDRFs was useful in predicting surgical outcome and event-free survival. The number of IDRFs should be considered in protocol planning, instead of IDRF presence or absence.

Current Treatment Patterns of Aplastic Anemia in China: A Prospective Cohort Registry Study.

Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.

The genetics and clinical characteristics of children morphologically diagnosed as acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is characterized by t(15;17)(q22;q21), resulting in a PML-RARA fusion that is the master driver of APL. A few cases that cannot be identified with PML-RARA by using conventional methods (karyotype analysis, FISH, and RT-PCR) involve abnormal promyelocytes that are fully in accordance with APL in morphology, cytochemistry, and immunophenotype. To explore the mechanisms involved in pathogenesis and recurrence of morphologically diagnosed APL, we performed comprehensive variant analysis by next-generation sequencing in 111 pediatric patients morphologically diagnosed as APL. Structural variant (SV) analysis in 120 DNA samples from both diagnosis and relapse stage identified 95 samples with RARA rearrangement (including 94 with PML-RARA and one with NPM-RARA) and two samples with KMT2A rearrangement. In the eligible 13 RNA samples without any RARA rearrangement at diagnosis, one case each with CPSF6-RARG, NPM1-CCDC28A, and TBC1D15-RAB21 and two cases with a TBL1XR1-RARB fusion were discovered. These uncovered fusion genes strongly suggested their contributions to leukemogenesis as driver alternations and APL phenotype may arise by abnormalities of other members of the nuclear receptor superfamily involved in retinoid signaling (RARB or RARG) or even by mechanisms distinct from the formation of aberrant retinoid receptors. Single-nucleotide variant (SNV) analysis in 77 children (80 samples) with RARA rearrangement showed recurrent alternations of primary APL in FLT3, WT1, USP9X, NRAS, and ARID1A, with a strong potential for involvement in pathogenesis, and WT1 as the only recurrently mutated gene in relapsed APL. WT1, NPM1, NRAS, FLT3, and NSD1 were identified as recurrently mutated in 17 primary samples without RARA rearrangement and WT1, NPM1, TP53, and RARA as recurrently mutated in 9 relapsed samples. The survival of APL with RARA rearrangement is much better than without RARA rearrangement. Thus, patients morphologically diagnosed as APL that cannot be identified as having a RARA rearrangement are more reasonably classified as a subclass of AML other than APL, and individualized treatment should be considered according to the genetic abnormalities.

Moss habitats distinctly affect their associated bacterial community structures as revealed by the high-throughput sequencing method.

To better understand the factors that influence the distribution of bacteria associated with mosses, the communities inhabiting in five moss species from two different habitats in Beijing Songshan National Nature Reserve were investigated using the high-throughput sequencing method. The sequencing was performed based on the bacterial 16S rRNA and 16S rDNA libraries. Results showed that there are abundant bacteria inhabiting in all the mosses sampled. The taxonomic analysis of these bacteria showed that they mainly consisted of those in the phyla Proteobacteria and Actinobacteria, and seldom were from phylum Armatimonadetes, Bacteroidetes and Firmicutes. The hierarchical cluster tree, based on the OTU level, divided the bacteria associated with all samples into two branches according to the habitat types of the host (terrestrial and aquatic). The PCoA diagram further divided the bacterial compositions into four groups according to both types of habitats and the data sources (DNA and RNA). There were larger differences in the bacterial community composition in the mosses collected from aquatic habitat than those of terrestrial one, whether at the DNA or RNA level. Thus, this survey supposed that the habitat where the host was growing was a relevant factor influencing bacterial community composition. In addition, the bacterial community detected at the RNA level was more sensitive to the habitat of the growing host, which could also be proved by the significantly differences in the predicted function by PICRUSt and the metabolically active dominant genera between different groups. This study expands the knowledge about the interactions between mosses and microbes.

Outcome of children with Langerhans cell histiocytosis and single-system involvement: A retrospective study at a single center in Shanghai, China.

BACKGROUND: This is a descriptive review of the clinical patterns and outcomes of children with Langerhans cell histiocytosis and single-system involvement (SS-LCH) treated at Shanghai Children's Medical Center. PROCEDURE: 60 evaluable newly diagnosed patients (37 boys, 23 girls) with a median age of 3.9 years (range: 0.3-15.3 years) and histiopathology-confirmed SS-LCH were enrolled from 2010 to 2014. All patients received systemic chemotherapy using either the DAL HX-83 or LCH-II protocol as determined by the physician. RESULTS: Bone was the most frequently affected organ (56/60, 93.3%). Of the 56 patients suffering from SS-bone disease, 35 (62.5%) had unifocal disease and 21 (37.5%) had multifocal disease. CNS-risk lesions were seen in nine patients (16.1%, 9/56) at diagnosis. Thirty-two patients were treated with the LCH-II protocol and 28 received the DAL HX-83 protocol. No patient received intralesional steroid injection at the time of surgery. CNS-risk lesion correlated with an inferior event-free survival (EFS) for patients with bone disease (62.5 ± 17.1% vs. 90.7 ± 4.5%; p = 0.039). The difference in the 5-year EFS between patients with unifocal and multifocal SS-bone LCH did not reach the statistical significance (93.8 ± 4.3% vs. 75.0 ± 9.7%; p = 0.074). No deaths were observed, leading to a 5-year OS of 100% in the present cohort of patients. Permanent consequences and secondary malignancies were not observed but were also limited by short follow-up. CONCLUSIONS: Optimal therapy for patients with SS-bone LCH has not been established. Less toxic therapeutic approaches should be considered for these patients and tested in prospective trials.

Treatment Outcome of Children With Multisystem Langerhans Cell Histiocytosis: The Experience of a Single Children's Hospital in Shanghai, China.

We reported the outcome of 150 children newly diagnosed with multisystem langerhans cell histiocytosis following a langerhans cell histiocytosis-II-based protocol (arm B). However, the continuation treatment was extended to 56 weeks and etoposide was omitted from the continuation treatment. Risk organ (RO) involvement was defined as: liver (≥3 cm with or without functional impairment); spleen (≥2 cm below the costal margin in the midclavicular line); hematopoietic system (hemoglobin <100 g/L, and/or white blood cell count <4.0×10/L, and/or platelets <100×10/L). The lungs are not considered a RO in the current study. For the 59 patients with RO involvement (RO+), the rapid response rate (week 6) was 61.0% and the 3-year overall survival 73.4%±5.9%. Rapid responders had a better 3-year survival rate than poor responders (90.9%±5.0% vs. 45.7%±11.0%, P<0.001). Ninety-one patients without RO involvement (RO-) had a relatively low 3-year cumulative reactivation rate (10.7%). No deaths occurred in this subgroup and the 3-year overall survival of RO- patients was 100%. Poor responders of RO+ patients had an extremely poor prognosis. An effective salvage therapy is essential for this high-risk group. The initial treatment intensity and duration of continuation therapy both impact disease reactivation in RO- patients.

Identification of fusion genes and characterization of transcriptome features in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a clonal malignancy of immature T cells. Recently, the next-generation sequencing approach has allowed systematic identification of molecular features in pediatric T-ALL. Here, by performing RNA-sequencing and other genomewide analysis, we investigated the genomic landscape in 61 adult and 69 pediatric T-ALL cases. Thirty-six distinct gene fusion transcripts were identified, with SET-NUP214 being highly related to adult cases. Among 18 previously unknown fusions, ZBTB16-ABL1, TRA-SALL2, and involvement of NKX2-1 were recurrent events. ZBTB16-ABL1 functioned as a leukemogenic driver and responded to the effect of tyrosine kinase inhibitors. Among 48 genes with mutation rates >3%, 6 were newly found in T-ALL. An aberrantly overexpressed short mRNA transcript of the SLC17A9 gene was revealed in most cases with overexpressed TAL1, which predicted a poor prognosis in the adult group. Up-regulation of HOXA, MEF2C, and LYL1 was often present in adult cases, while TAL1 overexpression was detected mainly in the pediatric group. Although most gene fusions were mutually exclusive, they coexisted with gene mutations. These genetic abnormalities were correlated with deregulated gene expression markers in three subgroups. This study may further enrich the current knowledge of T-ALL molecular pathogenesis.

Illumina sequencing of bacterial 16S rDNA and 16S rRNA reveals seasonal and species-specific variation in bacterial communities in four moss species.

In order to better understand the factors that influence bacterial diversity and community composition in moss-associated bacteria, a study of bacterial communities in four moss species collected in three seasons was carried out via high-throughput sequencing of 16S rDNA and 16S rRNA. Moss species included Cratoneuron filicinum, Pylaisiella polyantha, Campyliadelphus polygamum, and Grimmia pilifera, with samples collected in May, July, and October 2015 from rocks at Beijing Songshan National Nature Reserve. In total, the bacterial richness and diversity were high regardless of moss species, sampling season, or data source (DNA vs. RNA). Bacterial sequences were assigned to a total of 558 OTUs and 279 genera in 16 phyla. Proteobacteria and Actinobacteria were the two most abundant phyla, and Cellvibrio, Lapillicoccus, Jatrophihabitans, Friedmanniella, Oligoflexus, and Bosea the most common genera in the samples. A clustering algorithm and principal coordinate analysis revealed that C. filicinum and C. polygamum had similar bacterial communities, as did P. polyantha and G. pilifera. Metabolically active bacteria showed the same pattern in addition to seasonal variation: bacterial communities were most similar in summer and autumn, looking at each moss species separately. In contrast, DNA profiles lacked obvious seasonal dynamics. A partial least squares discriminant analysis identified three groups of samples that correlated with differences in moss species resources. Although bacterial community composition did vary with the sampling season and data source, these were not the most important factors influencing bacterial communities. Previous reports exhibited that mosses have been widely used in biomonitoring of air pollution by enriching some substances or elements in the moss-tag technique and the abundant moss associated bacteria might also be important components involved in the related biological processes. Thus, this survey not only enhanced our understanding of the factors which influence microbial communities in mosses but also would be helpful for better use and development of the moss-tag technique in the environmental biomonitoring.

Illumina sequencing-based community analysis of bacteria associated with different bryophytes collected from Tibet, China.

BACKGROUND: Previous studies on the bacteria associated with the bryophytes showed that there were abundant bacteria inhabited in/on these hosts. However, the type of bacteria and whether these discriminate between different bryophytes based on a particular factor remains largely unknown. RESULTS: This study was designed to analyze the biodiversity and community of the bacteria associated with ten liverworts and ten mosses using Illumina-sequencing techniques based on bacterial 16S rRNA gene. A total of 125,762 high quality sequences and 437 OTUs were obtained from twenty bryophytes. Generally, there were no obvious differences between the richness of bacteria associated with liverworts and mosses; however, the diversity was significantly higher in liverworts than in mosses. The taxonomic analyses showed that there were abundant bacteria inhabited with each bryophyte and those primarily detected in all samples were within the phyla Proteobacteria, Actinobacteria, Acidobacteria, Bacteroidetes, Armatimonadetes and Planctomycetes. In addition, bacteria assigned to Chloroflexi, Fibrobacteres, Gemmatimonadetes, Chlamydiae, group of TM6 and WCHB1-60 also appeared in part of the bryophytes. The assigned bacteria included those adapted to aquatic, anaerobic and even extreme drought environments, which is consistent with the bryophyte transition from aquatic to terrestrial conditions. Of them, approximately 10 recognized genera were shared by all the samples in a higher proportion, such as Burkholderia, Novosphingobium, Mucilaginibacter, Sorangium, Frankia, Frondihatitans, Haliangium, Rhizobacter, Granulicella and Hafnia, and 11 unclassified genera were also detected in all samples, which exhibited that large amounts of unclassified bacteria could interact with the bryophytes. The Heatmap and Principle Coordinate Analyses showed that bacteria associated with six mosses displayed a higher community similarity. Notably, the bacteria associated with another four mosses exhibited higher similarity with the ten liverworts. CONCLUSIONS: The result of further analysis of the bacterial community in different bryophytes revealed that the phylogeny of hosts might portray a strong influence on the associated bacterial community and that niche also played important roles when the hosts were phylogenetically more similar. Further studies are needed to confirm the role of phylogeny on bacterial communities and determine the level of influence on predicting which bacteria is associated with the host.

Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia.

Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4-IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.

Renal tumor in developing countries: 142 cases from a single institution at Shanghai, China.

BACKGROUND: The clinical management of children with renal tumors including Wilms' tumor, clear cell sarcoma, rhabdoid tumor and other renal tumors in our center was designed according to the National Wilms' Tumor Study Group protocols. METHODS: A total of 142 consecutive patients who had been diagnosed as having renal tumors at Shanghai Children's Medical Center were reviewed retrospectively in the period of December 1998 and September 2012. Diagnosis and treatment were decided by a multidisciplinary team including oncologists, surgeons, pathologists and sub-specialized radiologists. RESULTS: The median age of the patients at the time of diagnosis was 27 months. The tumor stages of the patients were as follows: stage I 24.6%, stage II 23.2%, stage III 32.3%, stage IV 14.1%, and stage V 5.6%. Favorable histology was diagnosed in 80.3%, anaplasia in 4.2%, clear cell sarcoma in 9.8%, rhabdoid tumor in 4.9%, and other renal tumors in 0.7% of the patients. The event-free and overall 5-year survival rates were 80% and 83%, respectively. Tumor relapse and progress was seen in 25 patients (17.6%). The median relapse time was 6 months (range: 2-37 months). Seven relapsing patients were retreated and four of them got second complete remission (three in stage II, one in stage I). CONCLUSION: A multi-disciplinary team work model is feasible in developing countries, and the renal tumors protocols basically from developed countries are safe in developing countries.

Treatment outcome of young children with acute lymphoblastic leukaemia: achievements and directions implied from Shanghai Children's Medical Centre based SCMC-ALL-2005 protocol.

This multicenter study used the Shanghai Children's Medical Center (SCMC)-ALL-2005 protocol for treatment of young patients (<2 years old) with acute lymphoblastic leukaemia (ALL), which was designed to improve treatment outcome in Chinese paediatric patients. These aims were pursued through risk-directed stratification based on presenting clinical and genetic features, minimal residual disease (MRD) levels and treatment response. All the patients achieved completed remission with 5-year event-free survivals of 82·6 ± 9·7% (low risk), 52·6 ± 8·4% (intermediate risk), 28·6 ± 17·1% (high risk). Disease recurrence was detected in bone marrow, bone marrow plus testis, testis alone and central nervous system in 16 (24·2%), 1 (1·5%), 1 (1·5%) and 1 (1·5%) patients respectively. No deaths were reported during induction. The SCMC-ALL-2005 trial for ALL patients <2 years old indicated high remission induction and low infection and treatment-related mortality rates.