Objective To investigate the relationship between serum-VEGF(sVEGF)and clinical features in children and adolescent patients with non-Hodgkin lymphoma(NHL) and acute lymphoblagtic leukemia(ALL).Methods The sVEGF in 101 of pretreated NHL and ALL patients were detected by enzymelinked inununosorbent assay(ELISA).The sVEGF prior and post-treatment were compared in 61 patients who achieved complete remission(CR).Results The median sVEGF was 567.70 ng/L in 81 prior-treated NHL patients.It was significantly higher than that in normal controls(P＜0.001).The median sVEGF wag 253.90 ng/L in 49 patients with CR,which was significantly different compared to pretherapeutic level(P＜0.001),whereag no statistical difference was observed compared to the normal controls. No relationships were found between sVEGF and clinical indexes such as clinical stage,Bsymptoms,gender,performance status(PS)score,bulk and serum lactate dehydrogenage (LDH)et al in untreated NHL patients.The median sVEGF was 198.60 ng/L in 20 untreated ALL patients.which wag no statistically different in comparison with that of normal controls.And the median sVEGF wag 181.73 ng/L in 12 of the CR ALL patients.which wag not statistically different in comparison with that in prior-treatment group or normal controls.Conclusion This study showed that the sVEGF in untreated children and adoleseent patients with NHL were higher than that of normal controls.The high sVEGF dmpped after achieving CR.There was no relationship between the level of sVEGF and clinical characteristics in the NHL patients.The sVEGF level in untreated ALL patients wag not difierent compared to that of the normal controls.and there was no change for sVEGF after chemotherapy in ALL patients.

Objective: To investigate the relationship between expression of programmed cell death ligand-1(PD-L1) in the tissue of neuroblastoma (NB) and patient's clinical characteristics and prognosis. Methods: Clinical data and surgical tissue paraffin blocks of 100 newly diagnosed NB children at Sun Yat-sen University Cancer Center between January 2000 and December 2015 were collected and the expression level of PD-L1 and its' relationship with pathological parameters and survival rate were analyzed retrospectively. The ratio between groups was compared by chi-square test. Kaplan-Meier method was used for survival analysis and COX regression model was used for multivariate analysis. Results: Among 100 cases, 71 were males and 29 females; there were 5 cases of stageⅠ, 4 cases of stageⅡ, 19 cases of stage Ⅲ, 65 cases of stage Ⅳ and 7 cases of stage Ⅳs. Ten out of 62 cases (16%) were N-MYC amplified; 15 cases were in low-risk group, 18 were in medium-risk group and 67 were in high-risk group. The positive rate of PD-L1 in NB tumor tissue was 57% (57/100), of which 55 were weakly positive, 1 was moderately positive and 1 was strongly positive. The positive rates of PD-L1 expression in tumor tissues without bone metastasis were higher than those with bone metastasis(66%(39/59)vs.44%(18/41), χ²=4.864, P=0.027), the positive rates of PD-L1 expression in tumor tissues pathologically diagnosed as neuroblastoma were higher than those pathologically diagnosed as ganglioneuroblastoma (61%(53/87) vs.31%(4/13), χ²=4.195, P=0.041), the positive rates of PD-L1 expression in tumor tissues originated from abdominal cavity were higher than those originated from other places (61% (51/83)vs.35%(6/17), χ²=3.937,P=0.047).The 4-year event-free survival (EFS) rates of patients with PD-L1 negative and positive were 40% and 33% (χ²=0.009, P=0.923), respectively. The 4-year overall survival (OS) rates of patients with PD-L1 negative and positive were 62% and 58% (χ²=0.294, P=0.587). Among 33 non-high-risk patients, the 4-year EFS rates of patients with PD-L1 negative and positive were 89% and 78% (χ²=0.001, P=0.965), the 4-year OS rates of patients with PD-L1 negative and positive were 100% and 96% (χ²=0.500, P=0.480). Among 67 high-risk patients, the 4-year EFS rates of patients with PD-L1 negative and positive were 24% and 11% (χ²=1.154, P=0.282), the 4-year OS rates of patients with PD-L1 negative and positive were 48% and 41% (χ²=0.692, P=0.405). Multivariate analysis showed that N-MYC gene amplification was an independent adverse prognostic factor for OS and EFS rates of NB patients (RR: 1.726,95%CI:1.209-2.466; RR:1.326,95%CI:1.014-1.736) and advanced clinical stage was an independent adverse prognostic factor for EFS rates of NB patients (RR: 26.498, 95%CI:3.518-199.614). Conclusions The expression of PD-L1 in NB tumor tissues was correlated with the clinical characteristics of children. However, there were no significant differences in the prognosis of patients with or without PD-L1 expression.

ObjectiveTo investigated the effect of post-operative primary site radiotherapy on stage Ⅳ neuroblastoma.Methods From Jan 2003 to Dem 2010,47 newly diagnosed stage Ⅳ neuroblastoma treated in Sun Yet-sen university cancer center.The treatment protocol for these patients were induction chemotherapy 4- 12 cycles,followed by surgery if possible,then 4-6 cycles consolidation chemotherapy and/or primary site radiotherapy and maintenance immunotherapy.The median age was 4 years old,the median induction chemotherapy cycles was 5.37 patients received resection of the primary tumor (total resection and nearly gross resection).24 out of 37 received primary site radiotherapy.ResultsThe followup rate was 89％.34 cases were followed up more than 36 months.For patients with or without postoperative primary site radiotherapy,the local recurrence rate were 13％ ( 3/24 ) and 54％ ( 7/13 ),respectively ( P =0.016),the 3-year local control rate were 84％ and 47％,respectively ( χ2 =7.95,P =0.005 ).The 3-year overall survival rate were 56％ and 28％,respectively ( χ2 =5.44,P =0.020 ). There was no severe radiation side effect. Conclusions This study indicated that postoperative primary site after induction chemotherapy and surgery could reduce the local recurrence rate and possibly improve the overall survival rate of stage Ⅳ neuroblastoma.

Objective:To evaluate the consistency of individual iodine nutrition levels by serum iodine, plasma iodine and whole blood iodine, and to provide reference for iodine-related epidemiological investigation.Methods:Healthy adults aged 18 - 59 years were recruited from the Research Center of Environment and Health in Water Source Area of South-to-North Water Diversion of Hubei University of Medicine. Whole blood sample was collected and serum and plasma were separated. The content of iodine in serum, plasma and whole blood was determined by inductively coupled plasma mass spectrometry (ICP-MS), and the linear relationship, precision and accuracy of the standard curve of the detection method were evaluated. The difference of three kinds of blood iodine levels was analyzed by variance analysis of compatibility group design, and Passing-Bablok regression and Bland-Altman plot were used to evaluate the consistency between serum iodine and plasma iodine.Results:The linear range of iodine in serum, plasma and whole blood was 0.0 - 25.0 μg/L, and the correlation coefficients ( R2) were all > 0.999. The relative standard deviation of 8 mixed blood samples ranged from 1.9% to 4.3% ( n = 6), and the determination results of blood iodine certified standard substances were all within the reference range. The recovery rate of the added standard ranged from 99% to 106%. The iodine levels in serum, plasma and whole blood of 50 volunteers were (57.31 ± 8.06), (57.49 ± 8.50) and (33.89 ± 5.40) μg/L, respectively, and there was no statistically significant difference between serum iodine and plasma iodine ( P = 0.904). The results of Passing-Bablok regression showed that there was no statistically significant difference in bias between serum iodine and plasma iodine ( P = 0.538). The Bland-Altman plot indicated that the difference between serum iodine and plasma iodine was within the consistency limit. Conclusion:The results of plasma iodine and serum iodine are in good agreement, and plasma iodine can be used as an evaluation index of individual iodine nutrition level. But there is no consistency between whole blood iodine and serum iodine.

Objective: To investigate the effect of gross total resection on the local control and survival of patients with stage IV neuroblastoma (NB) and analyze the extent of surgical resection of primary tumors that affects patient survival. Methods: A total of 96 patients with stage Ⅳ NB who were admitted to the Sun Yat-Sen University Cancer Center between January 2000 and December 2011 were analyzed. The patients were treated with combined-modality therapy, including chemotherapy, surgery, and/or radiotherapy. The patients were divided according to the extent of surgical resection of primary tumor into the following groups: group A, biopsy or tumor removal of less than 50% of the primary lesion; group B, incomplete resection of more than 50% but less than 90% of the lesion; group C, removal of more than 90% of the lesion; and group D, complete resection with or without macroscopic residual tumors. The survival rates of each group were analyzed. Results: The median age of the 96 patients was 4.4 years, ranging from 1.2-18.8 years. The overall 3-year progression-free survival (PFS) and overall survival (OS) of the total patients were 32.8% and 36.7%, respectively. A total of 24 cases were assigned in group A, 10 in group B, 23 in group C, and 39 in group D. Subgroup analysis revealed that the 3-year PFS rate was 17.5% for group A, 20.0% for group B, 45.1% for group C, and 40.5% for group D. The PFS rates were not statistically significant-ly different between groups A and B (P=0.352) and between groups C and D (P = 0.792). However, the OS was higher in groups C and D than that in groups A and B. The 3-year PFS rates were 42.2% and 17.8% for groups C and D (P<0.001), respectively. Conclu-sion: Resection extension of more than 90% of the primary tumor combined with chemotherapy and (or) radiation therapy can improve the survival of patients with stage Ⅳ NB. However, this treatment modality does not affect the treatment outcomes for minimal gross tu-mor residuals.

Objective: To investigate the impact of intensified maintenance therapy on the prognosis of children and adolescents with advanced lymphoblastic lymphoma (LBL) . Methods: Retrospective analysis on the treatment results of children and adolescents with stage Ⅲ and stage Ⅳ LBL who underwent BFM-NHL-90/-95 regimen without prophylactic radiotherapy. The intensified therapy group included the patients admitted from 1998 to 2005, while others were classified as the non-intensified therapy group. Patients in the intensified therapy group were intravenously treated with "etoposide phosphate plus cytrarabine" and high-dose methotrexate alternately per 2.5-3 months in addition to the oral chemotherapy with 6-mercaptopurine and methotrexate during the maintenance phase. Results: A total of 187 LBL patients were enrolled. The rates of 5-year event free survival were (76.9 ± 5.8) % and (77.9 ± 4.3) % (χ²=0.249, P=0.617) respectively, in the intensified therapy (n=52) and the non-intensified therapy groups (n=135) , while the rates of 5-year overall survival of them were (78.8 ± 5.7) % and (79.8±4.1) % (χ²=0.353, P=0.552) , respectively. Stratified by stage, immunological type as well as risk stratification, the rates of long-term survival were similar between the two groups. During the maintenance phase, the rates of grade Ⅲ and Ⅳ myelosuppression in the intensified therapy and the non-intensified maintenance groups were 55.8% and 18.5%, respectively (χ²=25.363, P<0.05) . Conclusion Intensified maintenance therapy failed to improve the prognosis of patients with advanced LBL.

Objective: To investigate the expression of B7H3 in neuroblastoma (NB) tissues and its relationship between clinical characteristics and prognosis of patients. Methods: The clinical data and pathological wax of 100 cases with neuroblastoma admitted from January 2000 to December 2015 in Sun Yet-Sen University Cancer Center were collected.The expression of B7H3 in tumor tissues was detected by immunohistochemistry (IHC) and then the expression of B7H3 and its relation to pathological parameters and survival rate of patients were analyzed. Results: (1) The positive rates of B7H3 in tumor tissues were 79% (79/100 cases), of which 37 were weak positive, 31 were mode-rate positive, 11 were strong positive, 58%(58/100 cases) showed low expression and 42%(42/100 cases) showed high expression.(2)The positive rate of B7H3 was positively correlated with the risk stratification, age, stage, primary site and N-MYC gene status (r=0.621, 0.350, 0.730, 0.224, 0.335; all P<0.05). (3)The high expression rates of B7H3 were positively correlated with the risk, stage, N-MYC gene status and tumor size (r=0.177, 0.016, 0.175, 0.284; all P<0.05). (4)B7H3 negative and positive 4-year event free survival (EFS) rates of 100 patients were 89.5% and 19.9% (χ²=31.260, P<0.001), 4-year overall survival(OS) rates were 94.7% and 48.3% (χ²=20.212, P<0.001), for 33 non-high-risk patients, B7H3 negative and positive 4-year EFS rates were 100.0% and 47.3% (χ²=8.760, P=0.003), and 4-year OS rates were 100.0% and 93.8% (χ²=1.063, P=0.003), respectively.Sixty-seven high-risk patients with B7H3 negative and positive 4-year EFS were 50.0% and 15.4% (χ²=4.093, P=0.043), 4-year OS were 75.0% and 42.0%, respectively (χ²=1.872, P=0.171). (5)The 4-year EFS rates of 100 patients with B7H3 low expression and high expression were 41.8% and 27.1% (χ²=3.801, P=0.051), and 4-year OS rates were 58.6% and 63.8% (χ²=0.111, P=0.739), respectively.The 4-year EFS and OS rates for 33 non-high-risk patients with B7H3 low expression and high expression were 94.7% and 44.2% (χ²=9.122, P=0.003), 100.0% and 90.9% (χ²=2.000, P=0.157), respectively.The 4-year EFS and OS rates of 67 high-risk patients with high expression and low expression of B7H3 were 13.9% and 22.1% (χ²=0.061, P=0.805), 36.3% and 57.7%(χ²=2.060, P=0.151), respectively.(6)Multivariate analysis showed that OS and EFS in B7H3 positive patients were lower than those in B7H3 negative patients[RR 95%CI: 28.110 (2.430-325.148); P=0.008; RR 95%CI: 12.834 (2.669-61.715), P=0.001]. Conclusions The positive rate of B7H3 in neuroblastoma is high, and the expression level of B7H3 is closely related to the clinical characteristics of the patients.Positive B7H3 in tumor tissues is an independent poor prognostic factor.B7H3 may be one of the new prognostic indicators for NB.

OBJECTIVETo evaluate the long-term survival of children and adolescents with lymphoblastic lymphoma (LBL) treated by a modified NHL-BFM-90 protocol.

METHODSFrom March 1998 to November 2010, 107 untreated patients with LBL (age <18 years) were enrolled and stratified into three groups (R1, R2 and R3), according to the stage of disease and response to induction chemotherapy. All patients received different intensive chemotherapy regimens based on a modified NHL-BFM-90 protocol. Total treatment duration was 2 years.

RESULTSOf the 107 patients, 79 were boys and 28 were girls, with a median age of 10 years (range 2.5-18 years). Six patients (5.6%) were stage I/II, 101 (94.4%) stage III/IV. The R1, R2 and R3 groups accounted for 5.6%, 71.0% and 23.4%, respectively. 75.7% of the patients had T-LBL, and 24.3% was B-LBL. At a median follow-up duration of 60 months (range 1-186 months), 24 patients died. The 5-year event-free survival (EFS) and overall survival (OS) were 75.5% and 77.8 % for all patients, 100.0% and 100.0% for group R1, 84.5% and 87.5 % for R2, 44.0% and 44.0% for R3, 72% and 73.5% for T-LBL, 86.4% and 88.5% for B-LBL, respectively. Myleosuppression was the major toxicity and need aggressive management.

CONCLUSIONThe modified NHL-BFM-90 protocol is an effective therapy for children and adolescents with LBL in low and intermediate risk. T-LBL had the similar outcomes as B-LBL did. The patients in high-risk group had a poor survival and new protocols are needed.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; Asparaginase ; Child ; Child, Preschool ; Daunorubicin ; Disease-Free Survival ; Female ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prednisone ; Treatment Outcome ; Vincristine