[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.

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.

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.

[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.

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.

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.

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.

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.

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.

Clinical outcome of childhood lymphoblastic lymphoma in Shanghai China 2001-2010.

BACKGROUND: This retrospective cohort study analysed the clinical characteristics and outcomes of patients with childhood lymphoblastic lymphoma (LBL) treated in Shanghai, China. PROCEDURE: From 2001 to 2010, 108 evaluable patients ≤16 years of age who were newly diagnosed with biopsy-proven LBL were treated with one of three treatment protocols: CCCG-99, SCMC-T-NHL-2002, or LBL-CHOF-2006. RESULTS: Two patients had Stage I disease, 5 had Stage II, 55 had Stage III, and 46 had Stage IV. The immunophenotype was T-cell LBL in 92 patients (85.2%) and precursor B-cell LBL in 16 (14.8%). The abandonment rate was 11.5%. Twenty-five patients (23.2%) suffered from resistant disease, including 1 with isolated central nervous system (CNS) relapse. At a median follow-up of 40.4 months (range, 0-114 months), the 5-year probability of event-free survival (pEFS) was 63.9 ± 4.6% in all patients. The 5-year pEFS for patients with pB-LBL was better than for patients with T-LBL (100% vs. 61.3 ± 5.1%, P = 0.007). Patients who had achieved complete remission on day 33 of induction had significantly better pEFS than those who had not (78.8 ± 4.6% vs. 28.2 ± 9.0%, P = 0.000). Three of 25 patients who experienced resistant disease were alive at the end of the study period. CONCLUSIONS: The abandonment rate was lower for patients with LBL than for patients with acute lymphoblastic leukemia. Prophylactic cranial radiation can be omitted for patients with LBL even when advanced-stage disease is present, as intensive systemic chemotherapy with intrathecal therapy is sufficient to prevent CNS relapse. The survival of patients with resistant disease was very poor.

ATG-Fresenius S combined with cyclosporine a: an effective immunosuppressive therapy for children with aplastic anemia.

For the first time, we conducted a 2-center retrospective study to show the efficacy of antithymocyte globulin (ATG)-Fresenius S plus cyclosporine treatment of children with severe aplastic anemia. From March 1997 to May 2011, a total of 124 patients (median age, 7.5 y; range, 1.5 to 16 y) from 2 centers with acquired AA treated with an immunosuppressive therapy (IST) regimen, consisting of ATG-Fresenius S (5 mg/kg per day for 5 d) and cyclosporine, were enrolled. The response rate was 55.6%. The median time between IST and response was 6 (0.5 to 18) months. After a median follow-up time of 29 (6 to 153) months, the rates of relapse and clonal evolution were 3.2% and 0.8%, respectively. Overall, 17 patients (13.7%) died in this study: 14 resulted from sepsis, 1 resulted from intracranial hemorrhage, 1 occurred after hematopoietic stem cell transplantation, and 1 resulted from clonal disease progression. The 5-year overall survival rate for the entire cohort was 74.7%. IST responders had a better survival rate (100%) than nonresponders (70.7%). The use of ATG-Fresenius S plus cyclosporine as a first-line immunosuppressive treatment appeared to be effective for children with severe aplastic anemia in our study. ATG-Fresenius S could be another option in the treatment arsenal, especially in countries where the other ATG products are harder to acquire.

Outcomes of children with clear cell sarcoma of kidney following NWTS strategies in Shanghai China (2003-2021).

BACKGROUND: Although clear cell sarcoma of kidney (CCSK) is rare, it is the second most common renal tumor in children after Wilms' tumor. NWTS and SIOP are two major groups which had made tremendous efforts on renal tumors, but the strategies are different, for NWTS follows the upfront surgery principle providing definite pathology and the SIOP follows the upfront chemotherapy principle, each has its own advantages. Here we aimed to evaluate the outcomes of CCSK in China following NWTS strategies to analyze the prognostic factors. METHODS: For this multicenter retrospective study, a total of 54 patients were enrolled from three children's hospitals, between April 2003 and December 2021. Treatment comprised upfront radical nephrectomy, followed by radiotherapy and intensive chemotherapy. Clinical records were regularly updated. Prognostic factors and survival rates were evaluated. RESULTS: The 54 enrolled patients had a median age of 37 months (range, 4 months to 11.4 years). The stage distribution was 16% stage I (n = 9), 30% stage II (n = 16), 39% stage III (n = 21), and 15% stage IV (n = 8). Among stage IV, metastasis sites included the lung (n = 6), bone (n = 1), and intra-orbital/cervical lymph node (n = 1). After a median follow-up of 5.6 years, the 5-year event-free survival (EFS) was 82.4±5.4%, and overall survival was 88.1±4.6%. The EFS was 100% for stage I, 93.8 ±6.1% for stage II, 71.1±10.0% for stage III, and 68.6±18.6% for stage IV. Univariate analysis revealed that staging (III/IV), tumor rupture, and inferior vena cava tumor thrombus were inferior prognostic factors. Multivariate analysis revealed that tumor rupture was independent poor prognostic factor (P = 0.01, HR 5.9). Among relapsed patients, relapse occurred a median of 11 months after diagnosis (range, 4-41 months), and 50% (4/8) achieved a second complete remission after multiple treatment. None of the six lung metastasis patients received lung RT, only one patient developed a relapse and was salvaged by RT after relapse. CONCLUSIONS: Tumor rupture was independent poor prognostic factor. Upfront surgery of NWTS strategies can make a definite pathology diagnosis, but how to reduce tumor rupture during surgery is important especially in developing countries. The outcomes of patients with stage I-III CCSK in China were comparable to findings in other developed countries. Better outcomes were achieved in stage IV CCSK by using an intensive chemotherapy regimen including carboplatin, which require further confirmation by AREN0321. Lung RT may be safely omitted in selected patients who achieve a compete radiographic response after 6 weeks of systemic treatment (including surgery). Treatment should be encouraged even in CCSK cases with metastasis and relapse.

[Evaluation on protocol SCMS-ALL-2005 for childhood B lineage acute lymphoblastic leukemia].

OBJECTIVE: To reduce the risk of therapy related complication during the treatment and keeps the long term event free survival, and to evaluate the results and risk factors of SCMC-lymphoblastic leukemia (ALL)-2005 protocol. METHODS: Designed the new protocol SCMC-ALL-2005 based on the previous protocol XH-99 for ALL. Divided the patients into low, median and high risk groups depends on risk factors including day 33 and 55 minimal residual disease (MRD) level. The higher risk group, the more intensive therapy was given. All the cases were registed on pediatric oncology network database (POND). All the abandonment patients were counted as event. From May 1(st) 2005 to April 30(th) 2009, 351 children who were newly diagnosed as B lineage ALL were enrolled in this study. The prognoses relating to risk grouping, age, mutation gene and MRD level were analyzed. RESULTS: Up to June 30, 2011, 273 patients were followed up with median time 49 months (range 26 to 74 months). Three hundred and forty-five patients (98.29%) achieved complete remission on day 35 induction. 12 cases were younger than 1 year old (3.42%), 285 cases between 1 and 9 years old (81.20%), 54 cases 10 to 18 years old (15.38%). Five year event-free survival (EFS) was 34%, 72% and 63%, respectively. One hundred and fifty-six cases belonged to lowered risk (44.44%), 177 to middle risk (50.43%) and 18 to higher risk (5.13%). Five year EFS was 78%, 64% and 30%, respectively. In this study, 18 patients were detected positive for BCR/ABL, 3 for MLL/AF4, 16 for PBX/E2A, and 36 for TEL/AML. The 5 year EFS were 11%, 66%, 75% and 74%, respectively. A total of 300 cases were tested for MRD levels on day 35. Of them, 241 cases were with MRD ≤ 0.01% (negative), and 59 cases > 0.01% (positive). The 5 year relapse free survival (RFS) was 79% and 58%, respectively. Total 6 patients died of complication (1.71%). 18 patients were abundant treatment with no disease progress. 70 patients relapsed (19.94%), including 52 bone marrow, 8 central nerve system (CNS), 1 both in bone marrow and CNS, 1 second cancer (M(4)) and 8 testis. Five year overall survival (OS) and EFS are 84% and 69%. CONCLUSIONS: The risk of therapy related death is low with the protocol SCMC-ALL-2005. MRD affects the prognosis. The long term prognosis is poor for high risk group, with BCR/ABL and positive MRD.

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.

[Evaluation of early monitoring of cardiotoxicity induced by anthracyclines].

OBJECTIVE: Anthracyclines (ANT) are effective for leukemia and solid tumors. However the long-term life quality of patients is seriously affected by ANT-related cardiotoxicity. The aim of this study was to evaluate the value of two dimension echocardiography (2DE) and serum biochemical indicators in monitoring ANT-related cardiotoxicity. METHODS: Seventy children who received ANT chemotherapy (ANT dose: 124 ± 73 mg/m2) and were followed up for 22 ± 13 months were enrolled. 2DE with aspects of conventional indexes (left ventricular diameter and wall thickness, ejection fraction, E/A), myocardial performance index (MPI) and tissue Doppler imaging (TDI) were performed. Serum levels of troponin (CTnI) and brain natriuretic peptide (BNP) were measured. Thirty-seven healthy children served as the control group. RESULTS: There were no significant differences in conventional indexes of 2DE between the ANT and the control groups. The MPI of left and right ventricular in the ANT group increased significantly compared with that in the control group (0.237 ± 0.06 vs 0.203 ± 0.06, 0.171 ± 0.05 vs 0.140 ± 0.04 respectively; P<0.01). TDI showed the late diastolic peak velocity in the basal and middle sections of left ventricular, interventricular septum and right ventricular in the ANT group were significantly higher than the controls. There were significant differences in the ratio of early to late diastolic peak velocity of the middle section of left ventricular and the basal and middle sections of the interventricular septum between the two groups (P<0.05). The changes of MPI and TDI became more obvious with the increased dose of ANT. There were no significant differences in serum CtnI and BNP levels between the two groups. CONCLUSIONS: The heart function of patients who received ANT chemotherapy needs to be monitored for a long term. MPI and TDI can be used as early indexes for monitoring the heart function.

[Correlation between blood T-cell receptor rearrangement excision circles levels and severe infection in children with acute lymphoblastic leukemia].

OBJECTIVE: This study quantitatively examined signal joint T-cell receptor rearrangement excision circles (sjTRECs) levels in peripheral blood of children with acute lymphoblastic leukemia (ALL) at different stages in order to evaluate the role of sjTRECs in predicting severe infection postchemotherapy. METHODS: sjTRECs levels in peripheral blood were measured by fluorescent quantitation-polymerase chain reaction in 30 children with newly diagnosed ALL, 36 children with ALL who accepted chemotherapy but were not infected, 30 children with ALL who had severe infection after chemotherapy, and 50 normal children. RESULTS: Blood sjTRECs levels in the normal group (394 ± 270 copies/103 MNC) were significantly higher than those in the other three groups (P<0.05). Blood sjTRECs levels in the chemotherapy group without infection (96 ± 78 copies/103 MNC) were significantly lower than those in the newly diagnosed ALL group (210 ± 219 copies/103 MNC) (P<0.05). The chemotherapy group with severe infection showed the lowest blood sjTRECs levels (48 ± 40 copies/103 MNC) in the four groups. CONCLUSIONS: The measurement of blood sjTRECs levels might be helpful for predicting the occurrence of severe infection postchemotherapy in children with 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.

Outcome of Chinese children with unrelated donor hematopoietic stem cell transplantation.

BACKGROUND: To evaluate the prognostic factors and outcomes in Chinese children undergoing unrelated donor hematopoietic stem cell transplantation (UDT). METHODS: Retrospective analysis of clinical data from 53 consecutive children who received UDT from November 2002 to December 2007 in our center. RESULTS: The median recipient age was 8.4 years (range 1.5-21). With a median follow-up of 36 months (range 18-80), the probability of 3-year overall survival (OS) was 71.5%. Treatment-related mortality (TRM) was 19.0%, and 9.5% died after post-transplant leukemia relapse. Incidence of grades I-II, III-IV acute and chronic graft versus host disease (GVHD) was 63%, 29%, and 46%. There was significant difference in OS between patients older or younger than 10 years (50.0% vs. 84.8%, P = 0.003), patients with different underlying diseases (ALL, AML, CML, and non-malignant disease: 36.4%, 80.0%, 61.5%, and 100%, P = 0.001) and patients receiving either HLA 0-1 versus 2-3 loci high-resolution mismatched UDT (83.3% vs. 53.3%, P = 0.034). The OS was not affected by the stem cell source (peripheral stem cell 70.3%, bone marrow 87.5% vs. cord blood 62.5%, P = 0.542) or the severity of acute GVHD (grade 0-II 77.8% vs. grade III-IV 60.0%, P = 0.140). CONCLUSIONS: The important prognostic factors for OS after UDT were the degree of HLA match, the age of patient and the type of underlying disease. Patients < 10-year with non-malignant disease receiving 0-1 locus high-resolution mismatched UDT had the most favorable outcomes.