[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.

Cost-effectiveness analysis of dinutuximab ß for the treatment of high-risk neuroblastoma in China.

BACKGROUND: Dinutuximab ß can be used to treat children with high-risk neuroblastoma (NB). Due to its high price, whether dinutuximab ß is cost-effective for the treatment of high-risk NB remains uncertain. Therefore, assessing the cost-effectiveness of dinutuximab ß in children with high-risk NB is of high importance. METHODS: The health utilities and economic outcomes in children with high-risk NB were projected using a partitioned survival model. The individual patient data (IPD) of add-on treatment with dinutuximab ß (GD2 group) were derived from the literature, while the IPD of traditional therapy (TT group) were obtained from retrospective data of Shanghai Children's Medical Center. Treatment costs included drugs, adverse event-related expenses, and medical resource use. Utility values were obtained from the literature. Costs and quality-adjusted life-years (QALYs) were measured over a 10-year time horizon. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also conducted. RESULTS: Compared with the TT group, QALY increased in the GD2 group by 0.72 with an increased cost of $171,269.70, leading to an incremental cost-effectiveness ratio of 236,462.75$/QALY. DSA showed that the price of dinutuximab ß was the main factor on the results than other parameters. Compared with the TT group, the GD2 group could not be cost-effective in the PSA at the $37,920/QALY threshold. CONCLUSION: Results found that dinutuximab ß is not a cost-effective treatment option for children with high-risk NB unless its price is significantly reduced.

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.

Microbiologically Documented Bloodstream Infection in Children With Malignancies: A Single-center Experience.

BACKGROUND: Bloodstream infection (BSI) remains a considerable cause of morbidity and mortality for cancer patients. With a better understanding of it, better methods can be used. The primary objective of this study was to describe the characteristics of BSIs in our institution, and the second was to determine the possible risk factors associated with them. MATERIALS AND METHODS: Data of cancer patients from 2009 to 2015 at our institution were included. Medical information and blood cultures were analyzed to determine the BSI rate. The χ and Fisher exact tests were used for categorical data and to determine risk factors associated with BSIs and pathogens. RESULTS: A total of 565 (8.6%) events were diagnosed with BSIs. Although Gram-negative bacteria (52.6%) were the most commonly isolated pathogens, Gram-positive microorganisms (45.0%) were also prevalent. Oral and gastrointestinal organisms were common. Pathogens were more likely to be identified in patients with central venous catheters and in patients with prolonged neutropenia (P<0.05). CONCLUSIONS: This study provides updated epidemiology in BSIs and helps with the prevention and management of suspected BSIs in vulnerable patients. Better anti-infection therapy could be provided to these patients based on the isolated pathogens.

Composite Adrenocortical Carcinoma and Neuroblastoma in an Infant With a TP53 Germline Mutation: A Case Report and Literature Review.

Li-Fraumeni syndrome is a kind of hereditary cancer predisposition syndromes, and is caused by TP53 gene mutation. Adrenocortical carcinoma (ACC) is commonly described as the most closely related tumor with this disease. Here, we present a case of a male infant with composite ACC and neuroblastoma who inherited a TP53 gene mutation from his mother, a 20-year-old carrier without any tumor to date. This TP53 gene mutation may be pathogenic and lead to composite malignancies of ACC and neuroblastoma.

Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008: The first nation-wide prospective multicenter study in China.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. The trial Chinese Children Leukemia Group (CCLG)-ALL 2008 was a prospective clinical trial designed to improve treatment outcome of childhood ALL through the first nation-wide collaborative study in China. Totally 2231 patients were recruited from ten tertiary hospitals in eight cities. The patients were stratified according to clinical-biological characteristics and early treatment response. Standard risk (SR) and intermediate risk (IR) groups were treated with a modified BFM based protocol, and there was 25%-50% dose reduction during intensification phases in the SR group. Patients in high risk (HR) group received a more intensive maintenance treatment. Minimal residual disease (MRD) monitoring with treatment adjustment was performed in two hospitals (the MRD group). Complete remission (CR) was achieved in 2100 patients (94.1%). At five years, the estimate for overall survival (OS) and event-free survival (EFS) of the whole group was 85.3% and 79.9%, respectively. The cumulative incidence of relapse (CIR) was 15.3% at five years. The OS, EFS and CIR for the SR group were 91.5%, 87.9%, and 9.7%, respectively. The outcome of the MRD group is better than the non-MRD group (5y-EFS: 82.4% vs 78.3%, P = .038; 5y-CIR: 10.7% vs 18.0%, P < .001). Our results demonstrated that the large-scale multicenter trial for pediatric ALL was feasible in China. Dose reduction in the SR group could achieve high EFS. MRD-based risk stratification might improve the treatment outcome for childhood ALL.

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.

Development and Initial Validation of the Macrophage Activation Syndrome/Primary Hemophagocytic Lymphohistiocytosis Score, a Diagnostic Tool that Differentiates Primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome.

OBJECTIVE: To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis. STUDY DESIGN: The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20% constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples. RESULTS: Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from <1% for a score of <11 to >99% for a score of ≥123. A cutoff value of ≥60 revealed the best performance in discriminating pHLH from MAS. CONCLUSION: The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing.

Clinical presentation and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in China: A retrospective multicenter study.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous disease with major diagnostic and therapeutic difficulties. A large-scale multicenter study of pediatric HLH is still lacking in China. PROCEDURE: The Histiocytosis Study Group of the Chinese Pediatric Society conducted this retrospective study in 2014. A total of 323 patients diagnosed with HLH between 2011 and 2013 from 12 hospitals were registered. RESULTS: The median age at diagnosis was 2.2 years (range, 0-14.6 years), with a peak age of HLH onset at 0 to 3 years (63%). Mutations in HLH-related genes were found in 27.9% (24/86) patients who underwent genetic testing. PRF1, UNC13D, STXBP2 and LYST were the predominant genes involved. Sixteen patients (66.7%) presented with only monoallelic mutations in one gene. Epstein-Barr virus (EBV) infection was the major condition related to HLH, which was documented in 74.4% (201/270) of the patients who underwent EBV detection. Of 252 evaluable patients, 64.7% (163) achieved non-active disease at the eighth week and patients treated with a protocol containing etoposide presented higher remission rates (75.6% vs. 46.8%, P < 0.001). In multivariate analysis, a younger age at diagnosis (<12 months), platelet count less than 80×109 /L, central nervous system involvement, and initial treatment using a protocol without etoposide (not HLH-94/04) were independent prognostic factors indicating resistant disease. DISCUSSION: This study first multicenter assessment of HLH in China shows some different features in Chinese children with HLH compared with those in western countries, including older age, vulnerability to EBV infection, and a high proportion of patients with single monoallelic genetic mutations.

Screening of RB1 gene mutations in Chinese patients with retinoblastoma and preliminary exploration of genotype-phenotype correlations.

PURPOSE: Retinoblastoma (RB) sets the paradigm for hereditary cancer syndromes, for which medical care can change depending on the results of genetic testing. In this study, we screened constitutional mutations in the RB1 gene via a method combining DNA sequencing and multiplex ligation-dependent probe amplification (MLPA), and performed a preliminary exploration of genotype-phenotype correlations. METHODS: The peripheral blood of 85 retinoblastoma probands, including 39 bilateral and 46 unilateral, was collected, and genomic DNA was extracted. DNA sequencing was conducted first. MLPA analysis was applied for patients with bilateral RB with negative sequencing results and unilateral probands whose age at diagnosis was less than 1 year old. RESULTS: Thirty-four distinct mutations were identified in 40 (47.1%) of the 85 probands (36 bilateral and four unilateral), of which 20% (8/40) was identified by MLPA. The total detection rate in bilateral cases was 92.3% (36/39). Of the total mutations identified, 77.5% (31/40) probands with a mean age of 10.7 months at diagnosis had null mutations, and 22.5% (9/40) with a mean age of 13.5 months at diagnosis had in-frame mutations. Of the 31 probands with null mutations, bilateral RB accounted for 96.8% (30/31). Of the nine probands with in-frame mutations, 66.7% had bilateral RB. There were seven new mutations of RB1 identified in this report, including six null mutations and one missense mutation. Clinical staging of the tumor did not show obvious differences between patients with null mutations and in-frame mutations. CONCLUSIONS: Our results confirm that the type of mutation is related to age of onset and the laterality, but not staging of the retinoblastoma tumor. MLPA is a reliable method for detecting gross deletion or duplication of the RB1 gene. The combination of sequencing and MLPA improves the clinical diagnosis of RB.

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.

Comparison of oral aprepitant and intravenous fosaprepitant for prevention of chemotherapy-induced nausea and vomiting in pediatric oncology patients: a randomized phase III trial.

Background: Neurokinin-1 receptor antagonists have improved the management of chemotherapy-induced nausea and vomiting (CINV), but to date there has been no prospective comparison between oral aprepitant and intravenous fosaprepitant in pediatric oncology patients. Methods: Our study was a double-parallel study, and the distribution ratio was 1:1. Children aged 2-12 years who were undergoing moderate or highly emetogenic chemotherapy (MEC or HEC) were randomly assigned to receive ondansetron and dexamethasone combined with either a single dose of intravenous fosaprepitant (arm A), or 3 days of oral aprepitant (arm B). The primary outcome measure was the rate of complete response (CR) of CINV within the acute phase, defined as from the start through 24 hours after the last chemotherapy dose. Response during the delayed phase, overall response, and use of rescue antiemetics were also assessed. Results: We prospectively evaluated 108 eligible patients, including 55 receiving fosaprepitant. Study observations were made during a single cycle for each patient. The occurrence of CR in the acute phase was statistically higher for patients receiving fosaprepitant (95% vs. 79%, P=0.018<0.05). Modest differences were seen in CR rates during the delayed phase (71% vs. 66%, P=0.586), and overall response rate (69% vs. 57%, P=0.179). The use of antiemetic rescue medicines was similar between arms A (11%) and B (7%). Conclusions: Fosaprepitant produced more CRs of CINV in the acute phase than did aprepitant, although there were no statistical differences in delayed phase response, overall response, or use of rescue antiemetics. This study confirms the safety, efficacy, and potential advantages of fosaprepitant in reducing CINV in pediatric oncology patients. Trial Registration: ClinicalTrials.gov identifier: NCT04873284.

Improved outcome for children with non-high risk acute lymphoblastic leukaemia after using an ALL IC-BFM 2002-based protocol in Shanghai, China.

We report the outcome of 92 non-high risk children with acute lymphoblastic leukaemia (ALL) following a Berlin-Frankfürt-Münster (BFM) Intercontinental ALL -based protocol. Compared with a matched historical control group, we found a lower incidence of treatment-related early death (1·2% vs. 10·9%, P = 0·015), a higher 6-year event-free survival (75·4 ± 4·9% vs. 58·2 ± 6·7%, P = 0·02), reduced total in-hospital costs per person (US $) (10267·0 vs. 18331·0, P < 0·001) and fewer total in-hospital days (164 vs. 296, P < 0·001). This ALL-BFM based protocol was quite tolerable in our institution and will be extended to high-risk patients.

[Characteristics of RB1 gene mutations in Chinese patients with retinoblastoma].

OBJECTIVE: To study the characteristics of RB1 gene mutations in Chinese patients with retinoblastoma. METHODS: Peripheral blood samples of 35 patients with retinoblastoma were collected and genomic DNA was extracted. Multiplex PCR sequencing was carried out to identify RB1 gene mutations. Parents of 6 probands with RB1 mutations were also enrolled to identify the origins of mutations. RESULTS: Fourteen patients were found to have carried germline mutations, among whom 11 had bilateral tumors and 3 had unilateral tumors. Sixteen germline mutations were identified, among which 13 were pathological, which included 5 nonsense mutations (c.1072C > T, c.1333C > T, c.1363C > T, c.1399C > T, c.2501C > A), 4 missense mutations (c.920C > T, c.1346G > A, c.1468G > A, c.1861C > A), 2 frameshift mutations (c.1947delG, c.2403delA) and 2 large fragment deletions (c.139_168 del30, exon 8 deletion). Three were non-pathological mutations, including 2 intronic mutations (c.540-23 dupT, c.2664-10T > A) and 1 silent mutation (c.2192T > A). One carrier was identified among the 6 parents of children carrying a RB1 mutation. CONCLUSION: Screening for RB1 gene mutations in patients with bilateral or unilateral retinoblastoma can help to identify heritable mutations and provide important clues for genetic counseling and clinical management.

[Relationship between parental exposure to chemicals and risk of childhood acute leukemia].

OBJECTIVE: To investigate the relationship between parental exposure to chemicals and the risk of childhood acute leukemia. METHODS: An exploratory case-control study was conducted among 201 new cases of childhood acute leukemia under 15 years old who went to 3 children's hospitals in Shanghai, China from January 1, 2009 to December 31, 2010, as well as 201 sex- and age-matched children (as controls) who went to the child health care clinic or department of orthopedics in the above hospitals. A survey was performed by face-to-face interviews with children's mothers. RESULTS: The risk factors for childhood acute leukemia might include maternal exposure to total chemicals (diesel oil, gasoline, paints, insecticides, pesticides, herbicides, and chemical fertilizers) from 3 months before pregnancy to the end of pregnancy (OR = 2.9, 95%CI = 1.1 ∼ 7.8), paternal exposure to insecticides (OR = 10.1, 95%CI = 1.2 ∼ 82.9) and chemical fertilizers (OR = 9.5, 95%CI = 1.1 ∼ 79.6) within 3 months before pregnancy, maternal working experiences in agriculture and forestry before pregnancy (OR = 8.4, 95%CI = 1.4 ∼ 50.2) and in spinning, leather processing, decoration, and vehicle repair before pregnancy (OR = 3.0, 95%CI = 1.2 ∼ 7.9) and during pregnancy (OR = 3.2, 95%CI = 1.1 ∼ 9.6), and paternal working experiences in agriculture and forestry (OR = 9.6, 95%CI = 2.1-44.8) and in spinning, leather processing, decoration, and vehicle repair (OR = 2.3, 95%CI = 1.1-5.0). CONCLUSION: Parental exposure to chemicals may increase the risk of childhood acute leukemia in their offspring.

Measles, mumps, and rubella revaccination in children after completion of chemotherapy and hematopoietic stem cell transplantation: a single-center prospective efficacy and safety analysis.

BACKGROUND: Chemotherapy and hematopoietic stem cell transplantation (HSCT) can damage the immune system, and may result in a loss of protection from infectious diseases. This study aimed to evaluate the impact of these treatments on the decrease in antibody titers of the measles, mumps, and rubella (MMR) vaccine and seroconversion post-revaccination of MMR. METHODS: After completion of treatment for primary diseases, participants received an MMR revaccination. Antibody titers for MMR before revaccination were analyzed for all 110 children. After revaccination, 68 participants received a follow-up evaluation of  antibody titer and adverse reaction. RESULTS: Multivariable analysis showed that therapeutic schedules were the only factor correlated with lack of antibody titers for measles after completing treatment (P = 0.008), while for mumps and rubella, no statistically significant difference was observed. Importantly, our study clearly demonstrated positive seroconversion rates for measles (97.5%), mumps (81.0%), and rubella (93.2%), with antibody levels rising across the board and peaking at around 6 months following revaccination. However, 6 months after revaccination, a downtrend of antibody titer levels was observed, which is comparatively earlier than the waning immunity observed in healthy children. Furthermore, we found MMR revaccination to be safe, with only a single adverse reaction (local pain at the injection site) reported. CONCLUSIONS: MMR revaccination is immunogenic for the population. We suggest periodic monitoring of antibody titers, in addition to a booster vaccination, although the optimal timing of booster vaccination remains to be investigated further.

[Comparison of the efficacy of CCCG-97 and BFM-90 protocols in the treatment for children with mature B-cell non-Hodgkin's lymphoma].

OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of the CCCG-97 and BFM-90 protocols in the treatment of pediatric patients with B-cell non-Hodgkin's lymphoma (B-NHL) retrospectively, and to explore the optimal therapeutic strategy. METHODS: Forty-five consecutive untreated patients (age of 18 years or less) with newly diagnosed B-NHL (including Burkitt Lymphoma and diffuse large B-cell lymphoma), treated in our hospital between July 1999 and December 2008 were enrolled in this study. The patients were classified into 2 groups by different protocols. From July 1999 to December 2004, twenty-one 3- to 13.8-year-old children were enrolled in the CCCG-97 group, with 1 in stage I/II, and 20 in stage III/IV(St Jude staging). From January 2005 to December 2008, twenty-four 2.8- to 14.1-year-old cases were enrolled in the BFM-90 group, with 3 in stage I/II, and 21 in stage III/IV (St Jude staging). The survival rates were evaluated by Kaplan-Meier analysis. RESULTS: Forty of the 45 patients (88.9%) reached complete response (CR) after 2 courses of chemotherapy. In the CCCG-97 group, the CR rate was 95.2% (20/21 pts), while that in the BFM-90 group was 83.3% (20/24 pts). At a median follow-up time of 62 (17 to 131) months, the 5-year event-free survival (EFS) was 71.8% for all patients, and 69.1% for Stage III/IV, respectively. In the CCCG-97 group, the 3-year EFS was 76.2%. In the BFM-90 group, it was 75.0%. There was no significant difference in survival rates between the CCCG-97 and BFM-90 groups (P=0.975). Unfavorable events recorded were as follows: Death of progression before achieving CR during induction therapy in 4 cases, and relapse after achieving CR in 6 cases. The relapse rates were 19.0% (4/21 pts) in the CCCG-97 group and 8.3% (2/24 pts) in the BFM-90 group, with a non-significant statistical difference (P=0.292). Major toxicities were myelosuppression and mucositis, especially in the BFM-90 group, but were tolerable and manageable. five patients in the BFM-90 group received rituximab, 2 patients (Stage III) achieved CR, while the other 3 patients (Stage IV) had progressive disease or relapse. CONCLUSIONS: Short-pulse and intensive chemotherapy, stratified according to stage of disease, can improve the survival rate of pediatric mature B-NHL. The efficacy of the CCCG-97 protocol and BFM-90 protocol is comparable and the toxicity is tolerable.