Search

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.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.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, P0.001) 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, P0.001) were independent factors of a favorable EFS.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.

OBJECTIVE: To investigate the distribution of body mass index (BMI) and risk factors for obesity in children with Diamond-Blackfan Anemia (DBA). METHODS: The children with DBA who attended National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from January 2003 to December 2020 were enrolled as subjects. The related clinical data and treatment regimens were recorded. The height and weight data measured within 1 week before or after follow-up time points were collected to calculate BMI. The risk factors for obesity were determined by multivariate regression analysis in children with DBA. RESULTS: A total of 129 children with DBA were enrolled, among whom there were 80 boys (62.0%) and 49 girls (38.0%), with a median age of 49 months (range 3-189 months). The prevalence rate of obesity was 14.7% (19/129). The multivariate logistic regression analysis showed that the absence of ribosomal protein gene mutation was closely associated with obesity in children with DBA (adjusted OR=3.63, 95%CI: 1.16-11.38, adjusted P=0.027). In children with glucocorticoid-dependent DBA, obesity was not associated with age of initiation of glucocorticoid therapy, duration of glucocorticoid therapy, and maintenance dose of glucocorticoids (P>0.05). CONCLUSIONS: There is a high prevalence rate of obesity in children with DBA, and the absence of ribosomal protein gene mutation is closely associated with obesity in children with DBA.

OBJECTIVE: To study the association between paroxysmal nocturnal hemoglobinuria (PNH) clone and immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA). METHODS: A retrospective analysis was performed on the medical data of 151 children with SAA who were admitted and received IST from January 2012 to May 2020. According to the status of PNH clone, these children were divided into a negative PNH clone group (n=135) and a positive PNH clone group (n=16). Propensity score matching was used to balance the confounding factors, and the impact of PNH clone on the therapeutic effect of IST was analyzed. RESULTS: The children with positive PNH clone accounted for 10.6% (16/151), and the median granulocyte clone size was 1.8%. The children with positive PNH clone had an older age and a higher reticulocyte count at diagnosis (P0.05). The positive PNH clone group had a significantly lower overall response rate than the negative PNH clone group at 6, 12, and 24 months after IST (P

OBJECTIVE: To study the efficacy and safety of early intratracheal administration of budesonide combined with pulmonary surfactant (PS) in preventing bronchopulmonary dysplasia (BPD). METHODS: A prospective randomized controlled trial was designed. A total of 122 infants with a high risk of BPD who were admitted to the neonatal intensive care unit of the Third Affiliated Hospital of Zhengzhou University from January to July 2021 were enrolled. The infants were randomly divided into a conventional treatment group with 62 infants (treated with PS alone at an initial dose of 200 mg/kg, followed by a dose of 100 mg/kg according to the condition of the infant) and an observation group with 60 infants (treated with PS at the same dose as the conventional treatment group, with the addition of budesonide 0.25 mg/kg for intratracheal instillation at each time of PS application). The two groups were compared in terms of the times of PS use, ventilator parameters at different time points, oxygen inhalation, incidence rate and severity of BPD, incidence rate of complications, and tidal breathing pulmonary function at the corrected gestational age of 40 weeks. RESULTS: Compared with the conventional treatment group, the observation group had a significantly lower proportion of infants using PS for two or three times (P0.05). CONCLUSIONS: Compared with PS use alone in preterm infants with a high risk of BPD, budesonide combined with PS can reduce repeated use of PS, lower ventilator parameters, shorten the duration of respiratory support, and reduce the incidence rate and severity of BPD, without increasing the incidence rate of glucocorticoid-related complications.

To analyze the clinical characteristics and factors affecting prognosis in children with severe aplastic anemia (SAA).Two hundred and five children with SAA treated in our department from January 2008 to April 2018 were selected, and the clinical characteristics and factors affecting prognosis were retrospectively analyzed.Among 205 SAA children, the effective rate (CR+PR) at 3, 6 and 12 months after immunosuppressive therapy (IST) treatment was 50.9%, 59.0% and 73.9%, respectively, and 5-year overall survival rate was 93.1%±2.0%. Univariate analysis showed that 5-year overall survival rate of SAA children of spontaneous delivery was higher than that of cesarean section (P=0.039), while multivariate analysis showed that birth way had no significant influence on 5-year overall survival rate (P0.05). The response rate at 3 months after IST of children with a recent history of decoration before SAA onset was higher than those without history of decoration (P0.05).Most of the SAA children can achieve high response rate and overall survival rate. Patients with recent history of home/school decoration may be the factor affecting hematological response after 3 months of IST, but have no influence on long-term overall survival.重型再生障碍性贫血患儿的临床特征及预后分析.分析重型再生障碍性贫血(SAA)患儿的基本临床特征及预后影响因素。.选择2008年1至2018年4月收治的SAA患儿205例，对其基本临床特征及预后影响因素进行回顾性分析。.205例SAA患儿中，免疫抑制治疗（IST）后3、6和12个月的有效率（CR+PR）分别为50.9%、59.0%和73.9%，患儿5年总生存（OS）率为93.1%±2.0%。单因素生存分析显示，顺产出生的SAA患儿较剖宫产出生者5年OS率高（P=0.039），多因素Cox回归模型分析显示，出生方式对SAA患儿5年OS率无显著影响（P0.05）。发病近期有装修材料接触史的SAA患儿IST后3个月反应率高于无装修材料接触史的SAA患儿（P0.05）。.SAA患儿经IST治疗后可获得较高的反应率和OS率，发病近期有家庭/学校装修材料接触史可能为SAA患儿IST后3个月反应率的影响因素，但对患儿长期生存未见显著影响。.

Forecasting of severe acute graft-versus-host disease (aGVHD) after transplantation is a challenging ‘large p, small n’ problem that suffers from nonuniform data sampling. We propose a dynamic probabilistic algorithm, daGOAT, that accommodates sampling heterogeneity, integrates multidimensional clinical data and continuously updates the daily risk score for severe aGVHD onset within a two-week moving window. In the studied cohorts, the cross-validated area under the receiver operator characteristic curve (AUROC) of daGOAT rose steadily after transplantation and peaked at ≥0.78 in both the adult and pediatric cohorts, outperforming the two-biomarker MAGIC score, three-biomarker Ann Arbor score, peri-transplantation features-based models and XGBoost. Simulation experiments indicated that the daGOAT algorithm is well suited for short time-series scenarios where the underlying process for event generation is smooth, multidimensional and where there are frequent and irregular data missing. daGOAT’s broader utility was demonstrated by performance testing on a remotely different task, that is, prediction of imminent human postural change based on smartphone inertial sensor time-series data.

Dasatinib, an orally administered Src-family kinase inhibitor, is combined with the standard chemotherapeutic regimen to enhance antineoplastic activity against core-binding factor acute myeloid leukemia (CBF-AML) in adults; however, limited data are available for use in children. In the present study, we studied the pharmacokinetics and safety of dasatinib in children.Dasatinib (60 or 80 mg/mTwenty pediatric patients (3.3-14.4 years of age) were included, and a total of 40 dasatinib concentrations were available for population pharmacokinetic analysis. The mean (standard deviation) of the estimated area under the concentration-time curve extrapolated to steady state (AUCThe population pharmacokinetics of orally administered dasatinib were evaluated in pediatric CBF-AML patients. The AUC

To retrospective analyze the reason of death in children with acute lymphoblastic leukemia (ALL) treated with CCLG-ALL 2008 protocol, and the experience was summarized in order to reduce the mortality.916 children diagnosed as ALL and accepted CCLG-ALL 2008 protocol from April 2008 to April 2015 in our hospital were enrolled, the dead cases in them were analyzed retrospectively.169 children died, including 111 (65.7%) males and 58 (34.3%) females. Recurrence was the main reason of death. 150 (88.7%) children died due to recurrence, among them, 86 (57.3%) cases gave up directly. The second reason of death was infection. The main clinical sites of infection were concentrated in respiratory system and digestive system. Bacterial infection was most common (Gram-negative was common).Enough finance and improving family compliance can decrease the mortality in children with ALL. Early rational use of antibiotics can reduce infection-related mortality in children with ALL.CCLG-ALL2008方案治疗儿童急性淋巴细胞白血病死亡病例分析.回顾性分析应用CCLG-ALL2008方案治疗儿童急性淋巴细胞白血病（ALL）患者的死亡原因，总结经验，以期降低患儿死亡率.2008年4月至2015年4月在本院诊断并接受CCLG-ALL2008方案治疗的儿童ALL患者共计916例，选取其中死亡的病例进行回顾性分析.死亡患者共169例，男性111例（65.7%），女性58例（34.3%）。复发为主要的死亡原因，由复发导致死亡的患者有150例（88.7%），其中86例（57.3%）复发后家属直接放弃治疗。第二死亡原因为感染，感染部位主要集中在呼吸系统和消化系统，以细菌感染为主（多见于革兰氏阴性杆菌）.加强经济支持、提高家属依从性可以降低儿童ALL的死亡率，早期合理地使用抗生素可以降低儿童ALL的感染相关死亡率.

OBJECTIVE: To study the clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). METHODS: A retrospective analysis was performed on the medical data of 14 children who were diagnosed with AML-MRC from June 2014 to March 2020, including clinical features, laboratory examination results, and prognosis. RESULTS: Among the 14 children with AML-MRC, there were 9 boys and 5 girls, with a median age of 11 years (range: 1-17 years), a median leukocyte count of 8.3×10(9)/L [range: (2.0-191.0)×10(9)/L], a median hemoglobin level of 73 g/L (range: 44-86 g/L), and a median platelet count of 75×10(9)/L [range: (4-213)×10(9)/L] at diagnosis. According to the FAB classification, the children with AML-M5 accounted for 71% (10/14). Among the 14 children, 4 had multi-lineage dysplasia (MLD), 2 had a history of myelodysplastic syndrome (MDS), 5 had MDS-related cytogenetic changes, 2 had MLD with MDS-related cytogenetic changes, and 1 had a history of MDS with MLD. The median follow-up time was 10.6 months (range: 0.4-54.4 months) for 14 children, among whom 2 gave up treatment immediately after diagnosis and 12 had an evaluable treatment outcome. The 2-year overall survival (OS) rate was 50%±15%, and the 2-year disease-free survival (DFS) rate was 33%±13%. Of the 12 children, 7 underwent haploidentical hematopoietic stem cell transplantation (HSCT), among whom 5 achieved DFS and 2 died, with a 2-year OS rate of 71%±17% and a 2-year DFS rate of 43%±19%; 5 children underwent chemotherapy alone, among whom 1 achieved DFS, 3 died, and 1 was lost to follow-up, with a 2-year OS rate of 40%±30% and a 2-year DFS rate of 30%±24%. There was no significant difference in the survival condition between the transplantation and chemotherapy groups (P > 0.05). CONCLUSIONS: Childhood AML-MRC is often observed in boys, and AML-M5 is the most common type based on FAB classification. Such children tend to have a poor prognosis. HSCT is expected to improve the poor prognosis of children with AML-MRC. However due to the small number of cases, it is necessary to increase the number of cases for further observation.

To analyze the outcomes of the children suffered from philadelphia chromosome positive acute lymphoblastic leukemia (Ph21 cases of firstly diagnosed PhAmong 21 patients, 17 were male and 4 were female with a median age of 8 years old (range, 4-12 years), the median follow-up time was 30 moths (range, 10-133 months). All the patients were treated with chemotherapy induced by the high-risk project of CCLG-ALL 2008. Among 14 patients treated with TKI plus chemotherapy, nine patients achieved complete remission. During 3 months after treatment, patients without complete molecular response or with the second complete remission and intensity desire of transplantation were treated with allo-HSCT, among 9 patients with allo-HSCT, six patients achieved long term survival.At TKI era, TKI combined with strong chemotherapy can make Ph21例Ph阳性急性淋巴细胞白血病儿童不同治疗疗效分析.分析Ph+急性淋巴细胞白血病（ALL）患儿TKI联合化疗和异基因造血干细胞移植（allo-HSCT）的疗效。.回顾性分析2008年1月至2015年4月在中国医学科学院血液病医院儿童血液病中心就诊应用CCLG-2008-ALL方案治疗的21例年龄12岁Ph21例患者中，男性17例，女性4例，中位年龄为8（4-12）岁，中位随访时间为58（10-133）个月。所有患儿均采用CCLG-2008-ALL高危组治疗方案诱导化疗，14例酪氨酸激酶抑制剂联合高危组巩固化疗的患者，至末次随访时间，9例患者获得长期生存； 治疗3个月时，对于未达到分子生物学缓解（5例）、复发重新获得缓解（2例）、有强烈移植愿望（2例）的患者行异基因造血干细胞移植，9例移植患者中6例患者获得长期生存。.在TKI时代，Ph

OBJECTIVE: To study the clinical significance of minimal residual disease (MRD) in B-lineage acute lymphoblastic leukemia (B-ALL) pediatric patients with different fusion gene backgrounds. METHODS: A retrospective analysis was performed on the medical data of 441 B-ALL children who were treated from January 2008 to April 2015. Among the 441 children, 336 had negative fusion gene, 79 had positive ETV6-RUNX1 fusion gene, and 26 had positive E2A-PBX1 fusion gene. Flow cytometry was used to detect MRD, and the influence of MRD on day 15 (TP1), day 33 (TP2), and week 12 (TP3) of induction therapy on prognosis was analyzed. RESULTS: In patients with negative fusion gene, the positive MRD group had significantly lower overall survival (OS) rate and event-free survival (EFS) rate (P < 0.05) and significantly higher recurrence rate and mortality rate at TP1, TP2, and TP3, compared with the negative MRD group (P < 0.05). In patients with positive ETV6-RUNX1, the positive MRD group had significantly lower OS and EFS rates (P < 0.05) and significantly higher recurrence rate and mortality rate (P < 0.05) than the negative MRD group only at TP1. In patients with positive E2A-PBX1, there were no significant differences in the OS rate, recurrence rate, and mortality rate between the positive and negative MRD groups at TP1, TP2, and TP3 (P > 0.05). CONCLUSIONS: MRD has the most definite prognostic significance in pediatric B-ALL patients with negative fusion gene, while it has unsatisfactory prognostic significance in those with positive ETV6-RUNX1 or positive E2A-PBX1.

To investigate the consistency between FCM and PCR on the detecting of MRD in TCF3-PBX155 cases of paediatric TCF3-PBX1Among the 55 children with TCF3-PBX1The detection result of MRD in TCF3-PBX1 detect by FCM and PCR shows better consistency. MRD positivity detected by FCM at the end of induction therapy (day 33) predicts a high risk of relapse in TCF3-PBX1 ALL patients.儿童TCF3-PBX1评价流式细胞仪（FCM）和逆转录-聚合酶链反应（PCR）2种方法检测TCF3-PBX1选取2008年4月到2015年4月本院收治的TCF3-PBX155例儿童TCF3-PBX1TCF3-PBX1

Pathogenic mutations in 3-keto-dihydrosphingosine reductase (KDSR) gene are associated with keratinization disorders and impaired platelet function. However, no case with both homozygotic mutation of

To study the long-term efficacy of CCLG-ALL2008 protocol used for treatment of childhood acute lymphoblastic leukemia (ALL).Nine hundred and forty children with newly diagnosed ALL from January 2008 to April 2015 were treated with CCLG-ALL2008 protocol. Overall survival (OS) and event-free survival (EFS) rates were estimated by the Kaplan-Meier method. Cox proportional hazards model was used for analyses of prognostic factors.Among the 940 newly diagnosed ALL patients, 570 patients were male, and 370 patients were female, the median age of onset was 5 years old (from 1 to 15 years old). The complete reaction rate (CR) was 96.7%. Survival analysis of 916 ALL patients with CR estimated by follow up [ (median follow up period 64 months (from 3 to 123 months) ] showed that, the expected 10 year OS rate was (78.6±1.5)% and the EFS rate was (66.0±1.8)%. The long-term OS rate of standard risk, intermediate risk and high risk patients was (93.0±1.5)%, (77.6±2.7)%, and (59.3±3.7)%, respectively, and the long-term EFS rate in standard risk, intermediate risk and high risk patients was (84.2±2.2)%. (67.8±2.9)%, and (42.1±3.9)% respectively. 10 year OS rate in B-ALL patients (79.8±1.6)% was significantly higher than that in T-ALL patients (53.5±6.3)% (P＜0.01). Among of all the patients, patients 201 (21.9%) relapsed, the median relapse time was 19 months (from 2 months to 81 months). The 10 year EFS rate was (81.7±3.7）% in the patients with MRD rate ＜0.01% after induction therapy, which was significantly higher than that in the patients with MRD rate＞0.01% (48.4±9.8)%.The therapeutic efficacy of the CCLG-ALL2008 protocol is closed to the level of supior study group in the world. Risk stratification can improve the outcome for childhood ALL. Immunophenotyping shows the outcome of B-ALL is better than that of T-ALL. MRD negative patients after induction therapy shows better prognosis compared with that of MRD positive patients.单中心应用CCLG-ALL2008方案治疗940例 儿童急性淋巴细胞白血病的长期疗效分析.分析应用CCLG-ALL2008方案治疗初诊急性淋巴细胞白血病（ALL）患儿的长期疗效.回顾性分析2008年1月至2015年4月期间，本院确诊为ALL的940例初诊患儿应用CCLG-ALL2008方案治疗的临床特征及疗效。采用Kaplan-Meier生存分析评估患儿总体生存（OS）率和无事件生存（EFS）率，运用COX回归比例风险模型分析影响预后的因素.940例初诊ALL患儿，男性570例，女性370例，中位年龄为5（1-15）岁。完全缓解（CR）率为96.7%。对获得完全缓解的916例患儿进行随访[中位随访时间为64（3-123）个月]的生存分析显示，预期10年OS率为（78.6±1.5）%，EFS率为（66.0±1.8）%。低危组10年OS率为（93.0±1.5）%，EFS率为（84.2±2.2）%；中危组10年OS率为（77.6±2.7）%，EFS率为（67.8±2.9）%；高危组10年OS率为（59.3±3.7）%，EFS率为（42.1±3.9）%。B-ALL的10年OS率（79.8±1.6）%、EFS率（67.7± 1.8）%，明显优于T-ALL的OS率为（63.6±5.6）%和EFS率为（53.5±6.3）%。复发201例（21.9%）中，复发中位时间为CR后19 （2-81） 个月。诱导缓解后微小残留病监测（MRD）≥0.01%者10年EFS为（48.4±9.8）%,明显低于＜0.01%患儿的EFS率（81.7±3.7）.CCLG-ALL2008方案对儿童初诊ALL疗效接近发达国家治疗的水平，危险分组是良好的个体化治疗指标。B-ALL预后优于T-ALL，诱导缓解后MRD阴性患者预后明显优于阳性患者.

Background: The peripherally inserted central catheter (PICC) has been widely used. However, there is still a lack of large sample size-based relevant risk factor investigation in children with blood diseases in china. Methods: We performed a retrospective, the single-center cohort study of child blood disease patients with PICC insertion. Totally, 2974 patients were enrolled for our study. Results: B-ultrasound plus Seldinger technology significantly improved the success rate of PICC insertion. The most common non-infectious complications were rash, followed by catheter blockage, mechanical phlebitis, and catheter broke. the male, 1-3 years old, Power PICC solo catheter and spring are risk factors for the rash. The power PICC solo catheter was the most important risk factor for catheter blockage. Insertion site under the elbow was the most important risk factor for phlebitis and catheter damage. Conclusion: Our finding first shed new light on the risk factors associated with PICC complications for Chinese blood disease children.

Acute lymphoblastic leukemia (ALL) is a common pediatric cancer. The second malignant neoplasms (SMNs) in long-term survivors of pediatric ALL are relatively rare. Herein we report a 10-year-old girl who was diagnosed as primitive neuroectodermal tumor (PNET) 5 years after the initial diagnosis of ALL with radiotherapy-free treatment. PNET is an exceedingly rare neoplasm in SMNs of survivors of childhood ALL. It is predisposed to be misdiagnosed and the pathogenesis is unclear. The outcome is poor. Long-term follow-up is necessary for the survival children of ALL.

OBJECTIVE: To study the clinical features and prognosis of core binding factor acute myeloid leukemia (CBF-AML) in children. METHODS: A retrospective analysis was performed from the chart review data of children who were newly diagnosed with CBF-AML in the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from August 2009 to November 2015. According to the type of fusion gene, the children were divided into CBFB-MYH11 and AML1-ETO groups. Clinical features and prognosis were analyzed and compared between the two groups. RESULTS: A total of 91 children with CBF-AML were enrolled in this study, among whom there were 74 (81%) in the AML1-ETO group and 17 (19%) in the CBFB-MYH11 group. Additional chromosomal abnormalities were observed in 38 children (42%), and deletion of sex chromosome was the most common abnormality and was observed in 28 children (31%). After the first course of induction treatment, the complete remission rate was 97% (88/91), the recurrence rate was 29% (26/91), the 5-year event-free survival (EFS) rate was 65%±6%, and the 5-year overall survival (OS) rate was 75%±5%. There were no significant differences between the AML1-ETO and CBFB-MYH11 groups in 5-year EFS rate (62%±7% vs 77%±11%, P > 0.05) or 5-year OS rate (72%±6% vs 88%±9%, P > 0.05). CONCLUSIONS: AML1-ETO is the main type of fusion gene in children with CBF-AML, and deletion of sex chromosome is the most common type of additional chromosomal abnormalities. Children with CBF-AML often have a good prognosis, and the children with AML1-ETO have a similar prognosis to those with CBFB-MYH11.

To study the effect of apoptotic drug Navitoclax (NTX) combined with chemotherapy drug Daunorubicin (DNR) on apoptosis of erythroleukemia cells.K562, HEL and TF-1 cells in logarithmic growth phase were treated with NTX, DNR and combination of the two drugs. CCK-8 test, Annexin V-DAPI double-staining flow cytometry, real-time RT-PCR were used to detect cell growth, cell apoptosis and expression of BAX, BAK, BCL-2, BCL-xl and BIM respectively. The effects of NTX, DNR and combination of the two drugs on apoptosis of K562, HEL and TF-1 cells were compared and analyzed.NTX combined with DNR could significantly inhibit the growth of K562, HEL and TF-1 cells; Apoptosis detection results showed that the apoptotic rate of K562, HEL and TF-1 cells in combination group was significantly higher than that in NTX and DNR single group; the expression level of apoptosis-related genes BAK and BAX in K562 cells in combination group was significantly higher than that in two single drug groups, and the expression level of anti-apoptotic protein genes BCL-2 and BCL-xl was significantly lower than that in two single drug groups (P＜0.05); the expression level of BAK in HEL cells treated with combined drugs for 24 hours was higher than that in DNR group (P ＜ 0.05); the expression level of BCL-2 in TF-1 cells treated with combined drugs for 24 hours was lower than that in two single drugs groups while the expression level of BAK in 48 hours was the highest in combined drugs group, and the expression level of BCL-2 and BCL-xl in combined drugs group was lower than that in NTX group (P＜0.05).NTX combined with DNR can significantly promote the apoptosis of erythroleukemia cell lines K562, HEL and TF-1, and induce the expression of apoptosis-related genes. This study provides a new scheme for the clinical treatment of erythroleukemia.Navitoclax联合柔红霉素促进红白血病细胞系K562、HEL和TF-1的凋亡.研究促凋亡药物Navitoclax（NTX）联合化疗药物柔红霉素（Daunorubicin，DNR）对红白血病细胞凋亡的影响.取对数生长期的K562、HEL和TF-1细胞，给予NTX、DNR以及2药联合，CCK-8检测细胞生长，Annexin V-DAPI双染流式细胞术检测细胞的凋亡，real-time RT-PCR检测凋亡相关基因BAX，BAK，BCL-2、BCL-xl、BIM的表达，对比分析NTX、DNR与2药联合对K562、HEL和TF-1细胞凋亡的影响.NTX联合DNR能明显抑制K562、HEL和TF-1细胞的生长；凋亡检测结果显示，联合用药组K562、HEL和TF-1细胞凋亡率明显高于NTX、DNR单用药组（P＜0.05）；凋亡相关基因检测结果显示，K562细胞前凋亡蛋白基因BAK、BAX的表达水平在联合用药组明显高于2个单药组,抗凋亡蛋白基因BCL-2、BCL-xl的表达水平明显低于2个单药组（P＜0.05）；HEL细胞联合用药24 h BAK的表达水平高于DNR单药组（P＜0.05）；TF-1细胞联合用药24 h BCL-2的表达低于2个单用药组，48 h BAK的表达联合用药组最高，BCL-2、BCL-xl的表达水平在联合用药组低于NTX单药组（P＜0.05）.NTX联合DNR能明显促进红白血病细胞系K562、HEL和TF-1细胞凋亡，诱导凋亡相关基因的表达。本研究期待为红白血病的临床治疗提供新方案.

OBJECTIVE: To study the clinical features and genetic mutations of children with Shwachman-Diamond syndrome (SDS) and malignant myeloid transformation. METHODS: Next-generation sequencing was used to analyze the gene mutations in 11 SDS children with malignant myeloid transformation, and their clinical features and genetic mutations were analyzed. RESULTS: Of the 11 children with SDS, 9 (82%) presented with refractory cytopenia of childhood (RCC), 1 (9%) had myelodysplastic syndrome with excess blasts (MDS-EB), and 1 (9%) had acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). The median age of onset of malignant myeloid transformation was 48 months (ranged 7 months to 14 years). Of the 11 children, 45% had abnormalities in the hematological system alone. Mutations of the SBDS gene were detected in all 11 children, among whom 5 (45%) had c.258+2T > C homozygous mutation and 3 (27%) had c.184A > T+c.258+2T > C compound heterozygous mutation. The new mutations of the SBDS gene, c.634_635insAACATACCTGT+c.637_638delGA and c.8T > C, were rated as "pathogenic" and "possibly pathogenic" respectively. The 3-year predicted overall survival rates of children transformed to RCC and MDS-EB/AML-MRC were 100% and 0% respectively (P=0.001). CONCLUSIONS: SDS children may have hematological system symptoms as the only manifestation, which needs to be taken seriously in clinical practice. The type of malignant transformation is associated with prognosis.

OBJECTIVE: To compare the efficacy of the CAMS-2005 and CAMS-2009 regimens in treating children with non-core binding factor acute myeloid leukemia (non-CBF AML) and to study the prognosis factors. METHODS: A total of 161 children who were initially diagnosed with non-CBF AML from April 2005 to December 2015 were enrolled as study subjects, and were divided into a CAMS-2005 regimen group (n=52) and a CAMS-2009 regimen group (n=109) according to the chemotherapy regimen provided. The efficacy was retrospectively compared between the two groups. RESULTS: The complete remission (CR) rate at the first course of treatment was higher in the CAMS-2009 regimen group than that in the CMAS-2005 regimen group (63.3% vs 46.2%; P < 0.05). There were no significant differences between the two groups in treatment-related mortality rate (11.9% vs 17.3%), recurrence rate (27.5% vs 28.8%), and three-year overall survival (OS) rate (44%±5% vs 28%±6%) (P > 0.05). Children who achieved CR at the first course of treatment had significantly higher OS and event-free survival rates than those who did not achieved CR (P < 0.01). CONCLUSIONS: The CAMS-2009 regimen is superior to the CAMS-2005 regimen in improving the CR rate in children with non-CBF AML after induction treatment. Whether CR is achieved at the first course of treatment can affect the OS rate of children with non-CBF AML.

To understand the epidemiological characteristics of childhood acute lymphoblastic leukemia (ALL) by analyzing the clinical data of 982 patients.A retrospective analysis was performed on 982 children with ALL who were admitted to our center from April 2008 to May 2015. The sex, age and season of onset, risk factors related with the disease, and molecular biological characteristics were analyzed.The ratio of male to female in ALL was 1.5∶1, the median age of onset was 5 years old, and the peak age of onset was 2 to 5 years old. The peak season of onset was spring. Analysis of birth and feeding history showed that the children born after normal period of gestation accounted for 98.0%. Among the born children 55.9% of children were born with natural lobour, and 44.1% of children were born by cesarean section. The breast feeding children accounted for 79.8%, while artificial/mixed feeding children accounted for 20.2%. The median birth weight was 3.5 kg (1.8-7.2 kg). There were 34 cases (3.5%) with abnormal birth history, including 10 cases with umbilical cord around the neck. 31.4% of the patients had a recent history of house decoration, and the median exposure time to decoration environment was 12 months (1-36 months). Among the first to third grade relatives of the children, 44 patients (4.5%) sufferd from blood system diseases, including 23 patients with leukemia, 53 (5.4%) had malignant tumors, and most of them were lung cancer, digestive system tumors and breast cancer. The immunophenotype showed that B-ALL accounted for 90.7% and T-ALL accounted for 9.3%. In molecular biological tests, TEL/AML1 positive patients accounted for 21.0%, E2A/PBX1 positive patients accounted for 5.2%, BCR-ABL positive patients accounted for 6.1%, and MLL positive patients accounted for 2.5%.The childhood ALL occurs in more boys, the peak age of onset is 2-5 years old, the peak season of onset is spring, the peak of birth season is autumn and winter, the proportion of cesarean section, high birth weight and non-breastfeeding after birth are higher than the average value of infants in most parts of the country during the same period. The proportion of childhood ALL patient's exposure to ionizing radiation and house decoration environment, and relatives with history of blood and malignant tumors are high.982例儿童急性淋巴细胞白血病流行病学研究.分析982例儿童急性淋巴细胞白血病（ALL）临床病例，了解儿童ALL流行病学特征.对本中心2008年4月至2015年5月收治的982例ALL患儿临床资料采用回顾性分析的方法，分析其性别、发病年龄、发病季节、发病相关危险因素及分子生物学特征等.ALL患儿男女比例为1.5∶1，中位发病年龄5岁，发病年龄高峰为2-5岁。发病高峰季节为春季。出生和喂养史分析显示，足月产患儿占98.0%；55.9%患儿是顺产，44.1%患儿是剖腹产。母乳喂养者占79.8%，人工混合喂养儿占20.2%。中位出生体重3.5 kg，其中巨大儿占18.3%。有出生异常史者34例（3.5%），其中脐带绕颈者10例。发病近期有家庭装修史者占31.4%，中位装修环境暴露时间12个月。患儿一至三级亲属中，有血液系统疾病者44例（4.5%），有恶性肿瘤者53例（5.4%）。免疫表型分析结果显示，B-ALL占90.7%，T-ALL占9.3%。分子生物学检测中，TEL/AML1阳性者占21.0%，E2A/PBX1阳性者占5.2%，BCR-ABL阳性者占6.1%，MLL阳性者占2.5.本研究中儿童急性淋巴细胞白血病男性患儿较多，发病年龄高峰为2-5岁，发病季节高峰为春季，出生季节高峰为秋冬季，剖宫产术分娩、出生时为巨大儿及出生后非母乳喂养比例高于同期全国大部分地区婴儿的均值，有电离辐射及家居环境暴露史与亲属血液病、恶性肿瘤病史者比例较高.

To analyze the therapeutic outcomes of acute lymphoblastic leukemia(ALL) patients with MLL gene rearrangement.Clinical outcomes of 28 ALL patients aged less than 12 years old with MLL gene rearrangement treated with Chinese Childhood Leukemia Group ALL 2008 (CCLG -ALL 2008) protocol from January 2008 to April 2015 were retrospectively analyzed.Among 28 patients, 14 were boys and 14 were girls, median age was 36(4-144) months and median follow-up period was 12.5 (ranged 2-106) months, and 10 were infants. All patients were given induction chemotherapy and the high-risk project of CCLG-ALL 2008. At the last time of follow-up, five patients gave up and were loss to follow-up. The 5 years OS and EFS were 52.2% and 47.8% respectively for the other 23 patients. The 5 years OS and EFS(28.6% and, 88.9%), (P=0.012), (28.6%, 77.8%), (P=0.048) rate of WBC≥50×10The 5 years OS is 52.2% and 5 years EFS is 47.8% for those ALL patients with MLL gene rearrangement. The WBC≥50×1028例MLL阳性急性淋巴细胞白血病患儿的治疗转归.分析MLL回顾性分析自2008年1月至2015年4月在中国医学科学院血液病医院儿童血液病中心就诊应用CCLG-2008-ALL方案治疗的28例年龄小于12岁MLL28例患者中男性14例，女性14例，中位年龄为36（4-144）个月，其中1岁以下患者共计10例。中位随访时间为12.5（2-106）个月。所有患儿均采用CCLG- 2008-ALL高危组治疗方案诱导及巩固化疗，直至末次随访日期（2019年6月1日），5例患者诱导治疗后早期放弃治疗，后期失访，剩余23例可分析的患者5年EFS和OS率分别为47.8%和52.2%。初诊时白细胞数≥50×10本研究中伴有MLL 阳性的急性淋巴细胞白血病患者5年OS率为52.2%，5年EFS率为47.8%。白细胞数≥50×10

To analyze the clinical efficacy and side effects of reduced-dose of cyclophosphamide combined cyclosporine A for severe aplastic anemia(SAA) children.Ten pediatric patients with SAA from January 2008 to May 2012 were enrolled. All the patients were treated with reduced dose of cyclophosphamide combined cyclosporine A. The dose of cyclophosphamide was 30 mg/(kg·d)×4 d, the dose of cyclosporine A gradually increased15 mg/L accroding to the blood concentration.The median follow-up time of the 10 pediatric patients was 100 months (6-126 months). Among 10 children with SAA, 4 cases achieved complete response(CR), 3 cases obtained partial response (PR) and the overall response rate was 70%, the remaining 3 cases showed no response (NR). One refractory patient treated by cyclophosphamide was progressed to paroxysmal nocturnal hemoglobinuria(PNH) at 25 months and was dead at 42 months after therapy.The results show that reduced-dose cyclophosphamide (30 mg/kg·d for 4 consecutive days) combinated with CsA (initial dose 4 mg/kg·d, and drugvallery concentration150 ng/ml) can make 7 of 10 children with severe aplastic anemia achieve complete response or partial response, and this regimen may be the second line regimen selected for some SAA children.减低剂量环磷酰胺联合环孢菌素A治疗重型再生障碍性贫血患儿的疗效分析.观察减低剂量环磷酰胺联合环孢菌素A治疗重型再生障碍性贫血（以下简称重型再障）患儿的疗效及副反应.自2008年1月到2012年5月就诊的10例重型再障患儿均接受减低剂量的环磷酰胺联合环孢菌素A治疗，具体应用剂量为环磷酰胺30 mg/(kg·d)×4 d，环孢菌素A起始剂量为4 mg/(kg·d), 后根据血药浓度调整用药剂量，使环孢菌素A谷浓度在150 ng/ml以上.中位随访时间为 100 (6-126) 个月，10例患儿中有4例获得完全缓解，3例获得部分缓解，总有效率为70%，其余3例无效。1例难治的重型再障患儿在应用环磷酰胺治疗后25个月进展为阵发性血红蛋白尿，治疗后42个月死于脑梗.减低剂量的环磷酰胺联合环孢菌素A使本组10例儿童重型再生障碍性贫血患者中7例获得缓解或部分缓解，为儿童重型再障患者提供一个备选的二线治疗方案.

OBJECTIVE: To study the association of platelet level at diagnosis with prognosis in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 892 children with ALL who underwent chemotherapy with the CCLG-ALL 2008 regimen were enrolled. According to the platelet count at diagnosis, these children were divided into normal platelet count group (platelet count ≥ 100×10(9)/L; n=263) and thrombocytopenia group (platelet count < 100×10(9)/L; n=629). The thrombocytopenia group was further divided into (50- < 100)×10(9)/L (n=243), (20- < 50)×10(9)/L (n=263), and < 20×10(9)/L (n=123) subgroups. The association of clinical features (sex, age, immunophenotype, and molecular biology) with event-free survival (EFS) and overall survival (OS) was analyzed. RESULTS: Compared with the thrombocytopenia group, the normal platelet count group had significantly lower positive rate of MLL gene rearrangement and recurrence rate (P < 0.05), as well as a significantly higher 10-year EFS rate (P < 0.05). There was no significant difference in 10-year OS between the two groups (P > 0.05). The normal platelet count group still had a significantly higher 10-year EFS rate than the thrombocytopenia group after the children with MLL gene rearrangement were excluded (P < 0.05), and there was still no significant difference in 10-year OS between the two groups (P > 0.05). The < 20×10(9)/L subgroup had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50- < 100)×10(9)/L subgroup, and the (20- < 50)×10(9)/L subgroup (P < 0.05). After the children with MLL gene rearrangement were excluded, the < 20×10(9)/L subgroup still had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50- < 100)×10(9)/L subgroup, and the (20- < 50)×10(9)/L subgroup (P < 0.05). CONCLUSIONS: ALL children with MLL gene rearrangement often have the clinical manifestation of thrombocytopenia. Platelet level at diagnosis is associated with the prognosis of ALL children. The children with normal platelet count have a low recurrence rate and good prognosis, and those with a platelet count of < 20×10(9)/L have the worst prognosis.

OBJECTIVE: To study the long-term clinical effect of CCLG-ALL2008 regimen in the treatment of children and adolescents, aged > 10 years, with newly diagnosed acute lymphoblastic leukemia (ALL). METHODS: A retrospective analysis was performed for the clinical data of 150 ALL children and adolescents aged > 10 years who were treated with CCLG-ALL2008 regimen from April 2008 to April 2015. The Kaplan-Meier method was used to analyze overall survival (OS) rate and event-free survival (EFS) rate. RESULTS: Among the 150 children and adolescents, there were 87 (58.0%) boys and 63 (42.0%) girls, with a median age of 11 years (range 10-15 years). Of the 150 children and adolescents, 84 (56.0%) had intermediate risk and 66 (44.0%) had high risk; 122 (81.3%) had B-lineage acute lymphoblastic leukemia (B-ALL) and 28 (18.7%) had T-lineage acute lymphoblastic leukemia (T-ALL). The fusion gene test yielded positive results in 51 children and adolescents (34.0%), among whom 16 (31%) had positive BCR-ABL, 11 (22%) had positive TEL-AML1, 8 (16%) had positive E2A-PBX1, and 16 (31%) were positive for other fusion genes. The complete remission rate was 96.0% (144/150) after one course of treatment with CCLG-ALL2008 regimen. The median follow-up time was 52 months (range 3-122 months). The 5-year OS rate was 79.0%±3.5%, and the 5-year EFS rate was 67.3%±4.1%. There were no significant differences in 5-year OS and EFS rates between the children with intermediate or high risk, as well as between the children with B-ALL or T-ALL (P > 0.05). The children and adolescents who achieved complete remission of bone marrow at the end of induction therapy had significantly higher 5-year OS and EFS rates than those who did not achieve complete remission (P < 0.05). CONCLUSIONS: In ALL children and adolescents aged > 10 years, CCLG-ALL2008 regimen can help to achieve high complete remission rate, 5-year OS rate and 5-year EFS rate. The children and adolescents failing to achieve complete remission at the end of induction therapy tend to have a poor prognosis.

Acute lymphoblastic leukemia (ALL) is a common pediatric cancer. The second malignant neoplasms (SMNs) in long-term survivors of pediatric ALL are relatively rare. Herein we report a 10-year-old girl who was diagnosed as primitive neuroectodermal tumor (PNET) 5 years after the initial diagnosis of ALL with radiotherapy-free treatment. PNET is an exceedingly rare neoplasm in SMNs of survivors of childhood ALL. It is predisposed to be misdiagnosed and the pathogenesis is unclear. The outcome is poor. Long-term follow-up is necessary for the survival children of ALL.

Pathogenic mutations in 3-keto-dihydrosphingosine reductase (KDSR) gene are associated with keratinization disorders and impaired platelet function. However, no case with both homozygotic mutation of KDSR and hepatic hemangioendothelioma has ever been reported due to its low prevalence. Here we report a seven months old Chinese boy with a homozygotic missense mutation in KDSR and both of his parents carry a same heterozygous mutation. He was born with thick plate-like scales overlying erythrodermic skin, but the skin symptoms were resolved spontaneously over the first month of his birth. He was also diagnosed with hepatic hemangioendothelioma at birth and accepted a resection surgery at 2 months old. At birth, his platelet count was severely low (10-20×109/L) with recurrent skin and gingival bleeding. Meanwhile, he suffered a mild normocytic, normochromic anemia with normal iron and hematinic levels. The anemia spontaneously recovered over the first 6 months, while the platelet count keeped at a low level (4-20×109/L). Treatment with corticosteroids, immunoglobulin or thrombopoietin was all suboptimal.

OBJECTIVE: To investigate the value of multiparameter flow cytometry (MFC) and flow cytometric scoring system (FCSS) in the diagnosis and prognostic evaluation of childhood myelodysplastic syndrome (MDS). METHODS: A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with MDS.MFC was performed to investigate the phenotype and proportion of each lineage of bone marrow cells.The correlations of FCSS score with MDS type, International Prognostic Scoring System (IPSS) score, and revised IPSS (IPSS-R) score were analyzed. RESULTS: Of all the 42 children, 20 (48%) had an increase in abnormal marrow blasts, 19 (45%) had a lymphoid/myeloid ratio of > 1, 14 (33%) had abnormal cross-lineage expression of lymphoid antigens in myeloid cells, 8 (19%) had abnormal CD13/CD16 differentiation antigens, 5 (12%) had abnormal expression of CD56, 3 (7%) had reduced or increased side scatter of granulocytes, 3 (7%) had reduced expression of CD36 in nucleated red blood cells, 2 (5%) had reduced expression of CD71 in nucleated red blood cells, 1 (2%) had absent expression of CD33 in myeloid cells, 1 (2%) had reduced or absent expression of CD11b in granulocytes, and 1 (2%) had absent expression of CD56 and CD14 in monocytes.There were significant differences in the median overall survival time and event-free survival time among the low-, medium-, and high-risk FCSS groups (P < 0.05).Among the low-, medium-, and high-risk FCSS groups, the low-risk FCSS group had the highest 2-year overall survival rate, while there was no significant difference between the medium-and high-risk FCSS groups (P > 0.05).The three groups had a 2-year event-free survival rate of 95%, 60%, and 46% respectively (P < 0.05).FCSS score was positively correlated with MDS type, IPSS score, and IPSS-R score (P < 0.05). CONCLUSIONS: MFC and FCSS help with the diagnosis and prognostic evaluation of childhood MDS.

To explore the HER22 expression in children with ETV6/RUNX1 (E/R)-positive acute lymphoblastic leukemia(ALL) and to investigate the relationship between the HER2 expression and clinical features.Thirty-seven newly diagnosed E/R-positive ALL children and 6 controls (4 cases of ITP and 2 healthy children) were selected in Institute of hematology and blood disease hospital. The 37 patients were divided into standard risk (SR), intermediate risk(IR), high risk(HR) groups according to risk stratification; and they were divided into relapse and non-relapse groups according to follow-up result. The CD10Among the 37 cases, 51.35% (n=19) were boys and 48.65% (n=18) were girls and their median age was 4.72 (1.72-11.99) years old. Among the 6 controls, 50% (n=3) were boys and 50% (n=3) were girls and the median age was 5.24 (1.53-13.17) years old. The expression level of HER2 in E/R-positive ALL patients were lower than that in controls (P0.05). Although the difference of HER2 expression level between the 2 groups failed to achieve statistical significance, the expression level of HER2 in relapse patients were significantly lower than that in non-relapse patients, and the HER2 expression in HR group patients were lower than that in SR and IR groups. In addition, there was no significant correlation between the expression level of HER2 and the sex, age, initial white blood cell count, blast cell percentage and the level of LDH (P0.05).The expression level of HER2 in E/R

Curved girder bridge can adapt to the complex needs of road, so it applies more and more. Because prestressed curved girder bridge is spatial structure, its deformation under load, prestress etc is very complicated. If ill-considered, it will cause accidents as cracking of beam body, too large transverse displacement and bearing disengaging etc. In this paper, by analysis of engineering examples, using ANSYS finite element analysis software modeling and calculating, we get the deformation law of small and medium span curved girder bridge under deadweight and prestress, and the law has guiding significance and practical value on design.

To describe characteristics of monocytes and histiocytes in the bone marrow of patients with a confirmed and suspected diagnosis of reactive histiocytosis.14 patients with a confident diagnosis of reactive histiocytosis or with a suspected diagnosis were inpatients at the Tianjin Blood Diseases Hospital between 2008 and 2012. Nucleated cells from bone marrow were observed by light microscopy - morphologically and immunohistochemically for histiocyte antigens - and ultrastructurally by transmission electron microscopy.Monocytes, atypical histiocytes, macrophages, hemophagocytes, reticular cells and dendritic cells were significantly increased in 9, 9, 5, 3, 3 and 2, respectively, of the 14 cases. Atypical histiocytes expressed some morphological characteristics of promonocytes.Monocytes, atypical histiocytes, macrophages, hemophagocytes, reticular cells and dendritic cells were increased in different relative degrees in patients with bone marrow reactive histiocytosis or suspected reactive histiocytosis. The increase in numbers of monocytes, atypical histiocytes and macrophages was a particularly significant feature. It is argued that atypical histiocytes with immature monocyte features might be precursors of hemophagocytes, reticular cells or dendritic cells.

OBJECTIVE: To investigate the association between clinical outcome and gene mutations in children with Fanconi anemia (FA). METHODS: A retrospective analysis was performed for the clinical data of six children with the same severity of FA and receiving the same treatment. At first, single cell gel electrophoresis and chromosome breakage induced by mitomycin C were performed for diagnosis. Then the gene detection kit for congenital bone marrow failure diseases or complementation test was used for genotyping of FA. Finally the association between the clinical outcome at 3, 6, 9, or 12 months after treatment and gene mutation was analyzed. RESULTS: Of all the six FA children, five had FANCA type disease, and one had FANCM type disease; four children carried two or more FA gene mutations. Among the children with the same severity of FA, those with more FA mutations had a younger age of onset and poorer response to medication, and tended to progress to a severe type. CONCLUSIONS: Children carrying more than two FA mutations have a poor clinical outcome, and hematopoietic stem cell transplantation should be performed as soon as possible.

OBJECTIVE: To identify the incidence of PAX5 deletion in childhood B-lineage acute lymphoblastic leukemia (B-ALL) without reproducible chromosomal abnormalities and to investigate the association between PAX5 abnormalities and prognosis of ALL. METHODS: Multiplex ligation-dependent probe amplification was used to determine the copy numbers of PAX5 gene in children newly diagnosed with B-ALL without reproducible chromosomal abnormalities between April 2008 and April 2013 and controls (children with non-hematologic diseases or tumors). The patients were classifiied into deletion group and non-deletion group based on the presence of PAX5 deletion. RESULTS: Eighteen (21%) out of 86 children with B-ALL had PAX5 deletion. The deletion group had a significantly higher total white blood cell count at diagnosis than the non-deletion group (P=0.001). The Kaplan-Meier analysis demonstrated that the deletion group had a significantly lower disease-free survival (DFS) rate than the non-deletion group (0.69±0.12 vs 0.90±0.04; P=0.017), but there was no significant difference in the overall survival rate between the two groups (P=0.128). The Cox analysis showed that PAX5 deletion was a risk factor for DFS (P=0.03). CONCLUSIONS: PAX5 deletion is an independent risk factor for DFS in B-ALL children without reproducible chromosomal abnormalities.

OBJECTIVE: To investigate the application of multiplex ligation-dependent probe amplification (MLPA) in the detection of copy number variations (CNVs) in pediatric ETV6/RUNX1-positive acute lymphoblastic leukemia (ALL), to compare this method with conventional karyotype analysis and fluorescence in situ hybridization (FISH), and to evaluate the value of MLPA. METHODS: The clinical data of 95 children with ETV6/RUNX1-positive ALL who were treated from January 2006 to November 2012 were analyzed retrospectively, including clinical features, results of karyotype analysis, and results of FISH. CNVs were detected with MLPA. RESULTS: CNVs were detected in 73 (77%), and the median number of CNVs was 1 (range 0-6). The CNVs of EBF1, CDKN2A/2B, PAX5, ETV6, RB1, and BTG1 were detected in more than 10% of all the patients. The changes in the chromosome segments carrying the genes with CNVs detected by MLPA were not detected by conventional karyotype analysis. The coincidence rate between the CNVs in ETV6 gene detected by FISH and those detected by MLPA was 66%. CONCLUSIONS: MLPA is an efficient and convenient method to detect CNVs in children with ETV6/RUNX1-positive ALL.

It’s a gas-liquid-solid three-phase reaction system in the reactor for flue gas desulfurization using pyrolusite pulp. Based on the two-film mass transfer theory and shrine core model, the macro-kinetics of flue gas desulfurization using pyrolusite pulp in a double magnetic stirred reactor were investigated. The effects of diffusion in solid film, surface chemical reaction, diffusion in liquid phase and gas phase of the process, have been carried out to distinguish the control step of the process. It was observed that SO2 absorption efficiency increased with the decreasing of pyrolusite particle size and varied gently when the pyrolusite particle diameter decreased to 0.18mm. SO2 absorption efficiency increased not significantly along with the increase of temperature and the liquid phase stirring speed but increased significantly along with the increase of the gas phase stirring speed. Experiment results showed that under simulated industrial conditions, gas phase diffusion was the control step compared to other related factors, given that pyrolusite particle diameter was kept below 0.1mm.

Congenital dyserythropoietic anemia I (CDA I) is a well-defined entity within the heterogeneous group of the CDAs. So far, most CDA cases were reported from Europe and Israel. A homozygous mutation of the CDAN1-gene was identified from a founder population observed in Bedouin tribes in Israel, and many different mutations in additional cases from Europe were reported. Few cases of CDA I were presented from Asian regions so far, mostly without convincing data and only one case in which a mutation of the CDAN1-gene was detected. Here, the first Chinese family with the typical hematological phenotype, osseous syndactyly and with a compound heterozygous CDAN1-gene mutation is described. Prevalence data of CDA I from Asian countries are not known, but experiences from Europe suggest that in many families the disorder remains undiagnosed.

To identify IKZF1 gene copy number abnormalities in BCR/ABL-negative B-lineage acute lymphoblastic leukemia (B-ALL) in children, and to investigate the association between such abnormalities and prognosis.Multiplex ligation-dependent probe amplification (MLPA) was applied to detect IKZF1 gene copy number abnormalities in 180 children diagnosed with BCR/ABL-negative B-ALL. These children were classified into IKZF1 deletion group and IKZF1 normal group according to the presence or absence of IKZF1 gene deletion. The association between IKZF1 copy number abnormalities and prognosis of children with BCR/ABL-negative B-ALL was analyzed retrospectively.Among 180 children, 27 (15.0%) had IKZF1 deletion; among the 27 children, 4 had complete deletions of 8 exons of IKZF1 gene, 17 had deletion of exon 1, 3 had deletions of exons 4-7, and 3 children had deletions of exons 2-7. Compared with those in the IKZF1 normal group, children in the IKZF1 deletion group had higher white blood cell (WBC) count and percentage of individuals with high risk of minimal residual disease at the first visit. IKZF1 deletions often occurred in BCR/ABL-negative children with no special fusion gene abnormalities. They were frequently accompanied by abnormalities in chromosomes 11, 8, 5, 7, and 21. The analysis with Kaplan-Meier method showed that disease-free survival (DFS) in the IKZF1 deletion group was significantly lower than that in the IKZF1 normal group (0.740 ± 0.096 vs 0.905 ± 0.034; P=0.002). Cox analysis showed that after exclusion of sex, age, initial WBC count, cerebrospinal fluid state at the first visit, prednisone response, and chromosome karyotype, IKZF1 deletion still affected the children's DFS (P0.05).Some children with BCR/ABL-negative B-ALL have IKZF1 deletion, and IKZF1 deletion is an independent risk factor for DFS in children with BCR/ABL-negative B-ALL.

To study the efficacy and safety of Chinese Childhood Leukemia Group ALL 2008 (CCLG-ALL2008) protocol combined with tyrosine kinase inhibitor (TKI, imatinib) for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in children.The clinical data of 53 patients aged less than 15 years when first diagnosed with Ph+ ALL between October 2008 and December 2013 were retrospectively analyzed. The patients were assigned to two groups: HR (n=26) and HR+TKI (n=27). The HR group was treated with CCLG-ALL2008 protocol (for high-risk patients). The HR+TKI group was treated with imatinib in combination with CCLG-ALL2008 protocol (for high-risk patients).The complete remission rate and chemotherapy induction-related mortality rate in the TKI+HR and HR groups were 100% vs 75% and 0 vs 15%, respectively. The 3-year event-free survival (EFS) rate in the HR group was (6±5)%; the 5-year EFS rate of the TKI+HR group was (52±11)%. Compared with the HR group, the TKI+HR group had no increase in the toxic responses to chemotherapy and had a decrease in the infection rate during the induction period.Application of imatinib significantly improves the clinical efficacy in children with Ph+ ALL and has good safety.

Based on stable isotopes in 409 precipitation samples provided by GNIP and meteorological records at the eight stations in Loess Plateau from January 1985 to December 2004, as well as the trajectory model of HYSPLIT 4.9, the spatial and temporal variations of d-excess and Δ18O were analyzed. The spatial distribution of secondary evaporation rate and the impact of meteorological factors on below-cloud secondary evaporation were also discussed. The result showed that: (1) During summer and winter monsoon periods, Δ18O showed an uptrend variation and d-excess showed a downtrend variation from south to north in Loess Plateau. From east to west, Δ180 showed an uptrend variation only in summer monsoon period and a downtrend variation in winter monsoon period. The value of d-excess also showed a downtrend variation. Amplitude of variation Δ18O and d-excess could indicate the routes of monsoon. (2) Secondary evaporation existed on an annual basis, and it was relatively significant during the summer monsoon period, with ranges from 1.51% to 5.88% and an average rate of 3.87%. While winter monsoon became lower, the rates ranged from 1.06% to 5.46%, and the average rate dropped to 3.03%. Monsoon had larger influence on secondary evaporation in margin area of the plateau, while the influence on the central stations was little. (3) Temperature had the highest contribution to secondary evaporation, followed by precipitation amount and water vapor pressure, and relative humidity had a small contribution. Moreover, the influence of wind speed and altitude on secondary evaporation was weak.

To ovaluate the prognostic value of prednisone response in treatment regimes of children with acute lymphoblastic leukemia.A total of 598 newly diagnosed ALL patients were enrolled and received prednisone pre-treatment. Based on the peripheral lymphoblast count on day 8, these patients were divided into 2 groups: prednisone good response (PGR) and prednisone poor response (PPR). PPR patients were classified into high risk group immediately and then received intensed chemotherapy. The all enrolled patients were followed up and the clinical features and treatment outcomes of the two groups were analyzed.Compared with PGR group, PPR group had different characteristics. They were older in age and had higher initial white blood cell count (P0.05). T-cell ALL (T-ALL) and Philadelphia chromosome positive ALL (Ph+ ALL) were frequent in PPR group (P0.05). Event-free survival (EFS) rate of PPR group was significantly lower than that of PGR group (P0.05). 2 year event-free survival(EFS) rate of PGR group was (88.3±1.5)%, while the 2-year EFS rate of PPR group was (58.4±5.3)%. 5 year EFS rates of PGR and PPR were (80.8±2.1)% and (53.4±6.0)%, respectively. The EFS rate of PPR group was falling rapidly within 2 years. PPR group had higher relapse rate, and most relapses occurred within 18 months (P0.05). PPR group had more high incidence of minimal residual disease (MRD) both on day 33 and on week 12 (P0.05). No significant difference of EFS and relapse time was found between PPR and high risk PGR patients (P0.05). In multi-variate regression analysis, the PPR, the presence of BCR-ABL1 and MLL were significantly unfavorable factors (P0.05).Prednisone response has been confirmed to be still great prognostic value and PPR children patients have poor outcomes generally. It is likely that the response to prednisone does not make much sense to high risk ALL patients.

To evaluate the copy number variations (CNV) of gene in pediatric acute myeloid leukemia (AML) and its correlation with clinical features and prognosis.The clinical data of 130 children aged14 years with newly diagnosed AML from May 2006 to March 2013 were analyzed restrospectively. The CNV were analyzed by multiplex ligation-dependent probe amplification (MLPA). Thirty-eight normal children were selected in control group. All the data were statistically analyzed using SPSS16.0 software.gene CNV of 2p24.3(MYCN), 10q23(PTEN) and 13q14(RB1, MIR15A, DLEU) were detected in more than 10% of the patients. CNV were detected in 49 cases(37.7%). The median loss and gain CNV frequencies per sample were 4. The CNV of TP53 correlated significantly with relapse. The loss ond gain CNV have no influence to EFS, DSF and OS. CNV were detected in the twelve percent of patients, but they were not detected with routine karyotype method.The MLPA technique combined with karyotyping makes a substantial increase in the diagnostic rate. Patients with TP53 alterations have significantly higher relapse rate.

To study the clinical features of children with relapsed acute lymphoblastic leukemia (ALL) treated with the CCLG-ALL2008 protocol.The data of 591 children who were newly diagnosed with ALL and were treated with the CCLG-ALL 2008 protocol between April 2008 and June 2013 were collected, and the clinical features of 80 children with relapsed ALL were retrospectively analyzed.After treatment with the CCLG-ALL2008 protocol, the recurrence rate in the standard-risk, intermediate-risk and the high-risk groups were 7.0%, 10.7% and 28.7% respectively (P0.05). The recurrence rate in patients with TEL/AML1-positive ALL was 8.0%, and the 5-year overall survival (OS) of the relapsed patients was 37.04%. The recurrence rates in patients with MLL-positive and BCR/ABL-positive ALL were 35.0% and 24.2% respectively, and none of the relapsed patients had long-term survival. The recurrence mainly occurred at the very early stage (53%), and none of patients with recurrence at the very early stage had long-term survival. The recurrence occurred at early stage and late stage accounted for 34% and 14% respectively, and the 5-year OS rates of patients with recurrence at early stage and late stage were 11.44% and 60.00% respectively. The sites of recurrence were mainly bone marrow alone (83%), and the 5-year OS of patients with recurrence at bone marrow alone was 9.23%. The recurrence in bone marrow and outside bone marrow accounted for 11%, and the 5-year OS of patients with recurrence in both bone marrow and outside bone marrow was 25.00%. The recurrence only outside bone marrow accounted for 6%, and the 5-year OS of patients with recurrence only outside bone marrow was 100%. The recurrence rate in patients with T-cell ALL was 9.5%, and none of the relapsed patients had long-term survival. The recurrence rate in patients with B-cell ALL was 14.3%, and the 5-year OS of the relapsed patients was 15.52%.After treatment with the CCLG-ALL2008 protocol, a relatively high recurrence rate is observed in children with high-risk ALL. Positive MLL and positive BCR/ABL are high-risk factors for recurrence. The recurrence rate is not significantly correlated with immunophenotype. A very low survival rate is seen in children whose recurrence have the following features: at early stage, only in bone marrow, T-cell ALL, and abnormal BCR/ABL and MLL.

To analysze genotype and measure telomere length in two Chinese patients with dyskeratosis congenita(DC).The peripleral blood DNA was extracted in two patients characterized by mucocutaneous abnormalities (abnormal nails, lacy reticulated skin pigmentation, and oral leukoplakia), bone marrow failure, DC genes were amplified by polymerase chain reaction (PCR), including DKC1, TERT, TERC, TINF2, NOP10, NHP2, then DNA sequencing was performed for abnormal exons. Lymphocyte telomere length was measured by flow cytometry-fluorescence in situ hybridization(Flow-FISH).Abnormal peaks were found in exon 6 of TINF2 gene of the two patients and a 811C→T transition in TINF2 gene in one patient. DNA sequencing showed a 848C→A transition in TINF2 gene in another patient. Relative telomere length was remarkable less than that of normal children with same age.Physician should think about DC if the young patients with mucocutaneous abnormalities and marrow failure. Early detection of related genes and measurernant of tolomere length may contribute to avoid misdiagnosis. TINF2 c.811C→T (Q271X) and TINF2 c.848C→A (P283H) exist in the two patients, it is reported in China for the first time.

To investigate the methylation rate of cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase inhibitor 2B (CDKN2B) in the 9P21 region in children with acute myeloid leukemia (AML) and the association of gene methylation with clinical features and outcomes.The clinical data of 58 children who were newly diagnosed with AML between January 2010 and December 2012 were retrospectively analyzed. Thirty-eight healthy children were recruited as the control group. Genomic DNA was extracted from bone marrow or peripheral blood of the 58 patients and 38 healthy children. The methylation status of CDKN2A and CDKN2B was analyzed by methylation-specific multiplex ligation-dependent probe amplification.Gene methylation was not found in healthy children. Methylation probes of 44 patients were detected in 58 patients. The methylation of CDKN2A was detected with 136 bp and 237 bp methylation probes. The methylation of CDKN2B was detected with 130 bp, 210 bp, 220 bp, and 417 bp methylation probes. The methylation rate of CDKN2A was 5%, while the methylation rate of CDKN2B was 76%. The methylation detected by some probes was associated with sex, hemoglobin, and platelet count at the first visit.The methylation of CDKN2B is a common event in children with AML, while the methylation of CDKN2A is relatively rare.

To study the clinical features of patients with refractory cytopenia of childhood (RCC).The clinical data of 1 420 children (0-14 years old) with an initial diagnosis of non-severe aplastic anemia between January 1990 and June 2013 were retrospectively analyzed. Bone marrow cell morphology and histopathology were re-evaluated, and the patients were re-classified using the criteria proposed in the 2008 edition of the World Health Organization classification of RCC in hematopoietic and lymphoid tumor tissues. The clinical outcomes were followed up every 3-6 months.Among all the 1 420 cases, 152 (10.7%) were reassessed as RCC. Patients with RCC had a lower level of hemoglobin and a higher percentage of fetal hemoglobin than those with non-severe aplastic anemia. Of the patients with RCC, 21.5% showed abnormal karyotypes at diagnosis. The median follow-up period for all patients was 36 months (ranging from 1 to 283 months). The rates of complete response, partial response, and no response to cyclosporine and androgen treatment in RCC patients were 19.0%, 26.7%, and 54.3%, respectively. The 5- and 10-year prospective overall survival rates of RCC patients were 87.9% and 72.4%, respectively. The 5- and 10-year prospective clonal evolution rates were 15.3% and 20.0%, respectively. The 2-year prospective incidence of newly diagnosed karyotype abnormality after the initial diagnosis was 3.6%. The 5- and 10-year prospective leukemia transformation rates were 10.0% and 20.0%, respectively.RCC shows clinical features similar to adult myelodysplastic syndrome. Children with RCC have a poor prognosis, an increased risk of transformation to leukemia, and a low response rate to cyclosporine treatment.