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1.
Thromb Res ; 210: 70-77, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35026611

RESUMO

INTRODUCTION: Purpura fulminans (PF) is a hematological emergency that can be caused by severe congenital protein C (PC) deficiency. It has been rarely reported in the Chinese population. We aimed to characterize the clinical and genetic features of Chinese pediatric patients with severe congenital PC deficiency who first presented with PF. MATERIALS AND METHODS: Twelve pediatric patients were diagnosed with severe congenital PC deficiency with PF, which was diagnosed based on our hospital records and previous reports from 1988 to July 2021 in China. We evaluated the clinical and genetic features of these patients. RESULTS: Nine patients (9/12, 75%) had onsets that were observed within the first 48 h after birth. Six patients had a family history of thromboembolism. There was no consanguinity. Other symptoms were intracranial thrombosis or hemorrhage (4, 33.3%), ocular lesions (2, 16.7%), gastrointestinal hemorrhage (2, 16.7%) and kidney infarction before birth (1, 8.3%). All but one of the patients (one case not detected) had a plasma PC activity of <10%. The genetic study indicated that in the eight patients with inherited PC deficiency, two were homozygous, five were compound heterozygous and one was heterozygous for PC deficiency. CONCLUSION: This is the first and largest case series of Chinese pediatric patients with severe congenital PC deficiency who first presented with PF. It has been shown that treatment with both fresh frozen plasma and anticoagulants is recommended when PC concentrate is not easily available, especially in developing countries.


Assuntos
Deficiência de Proteína C , Púrpura Fulminante , Trombofilia , Anticoagulantes/uso terapêutico , Criança , Humanos , Proteína C/metabolismo , Deficiência de Proteína C/complicações , Deficiência de Proteína C/genética , Púrpura Fulminante/tratamento farmacológico , Púrpura Fulminante/genética , Trombofilia/tratamento farmacológico
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(11): 1111-1118, 2021 Nov 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34753542

RESUMO

OBJECTIVES: To study the prognostic value of measurable residual disease (MRD) for childhood acute myeloid leukemia (AML) by analyzing MRD-guided risk stratification therapy. METHODS: A total of 93 children with AML were prospectively enrolled in this study. Chemotherapy with the 2015-AML-03 regimen was completed according to the risk stratification determined by genetic abnormality at initial diagnosis and MRD and bone marrow cytology after induction therapy I. Multiparameter flow cytometry was used to dynamically monitor MRD and analyze the prognostic effect of MRD on 3-year cumulative incidence of recurrence (CIR) rate, event-free survival (EFS) rate, and overall survival (OS) rate. RESULTS: The 93 children with AML had a 3-year CIR rate of 48%±6%, a median time to recurrence of 11 months (range 2-32 months), a 3-year OS rate of 65%±6%, and a 3-year EFS rate of 50%±5%. After induction therapy I and intensive therapy I, the MRD-positive children had a significantly higher 3-year CIR rate and significantly lower 3-year EFS and OS rates than the MRD-negative children (P<0.05). There were no significant differences in 3-year CIR, EFS, and OS rates between the MRD-positive children with a low risk at initial diagnosis and the MRD-negative children after adjustment of chemotherapy intensity (P>0.05). The multivariate analysis showed that positive MRD after intensive treatment I was a risk factor for 3-year OS rate in children with AML (P<0.05). CONCLUSIONS: MRD has predictive value for the prognosis of children with AML. Based on the MRD-guided risk stratification therapy, reasonable application of chemotherapy may improve the overall prognosis of children with AML.


Assuntos
Leucemia Mieloide Aguda , Criança , Progressão da Doença , Citometria de Fluxo , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Neoplasia Residual , Prognóstico
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 835-840, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511174

RESUMO

OBJECTIVES: To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria. METHODS: A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. According to the diagnostic criteria for ALAL by World Health Organization and European Group for the Immunological Characterization of Leukemias, the 39 children were divided into two groups: ALAL group (n=28) and myeloid expression group (n=11). The clinical features, treatment, and prognosis were compared between the two groups. RESULTS: The 34 children receiving treatment had a 3-year event-free survival (EFS) rate of 75%±9% and an overall survival rate of 88%±6%. The children treated with acute myeloid leukemia (AML) protocol had a 3-year EFS rate of 33%±27%, those treated with acute lymphoblastic leukemia (ALL) protocol had a 3-year EFS rate of 78%±10%, and those who had no remission after induction with AML protocol and then received ALL protocol had a 3-year EFS rate of 100%±0% (P<0.05). The children with negative minimal residual disease (MRD) after induction therapy had a significantly higher 3-year EFS rate than those with positive MRD (96%±4% vs 38%±28%, P<0.05). Positive ETV6-RUNX1 was observed in the myeloid expression group, and positive BCR-ABL1, positive MLL-r, and hyperleukocytosis (white blood cell count ≥50×109/L) were observed in the ALAL group. There was no significant difference in the 3-year EFS rate between the myeloid expression and ALAL groups (100%±0% vs 66%±11%, P>0.05). CONCLUSIONS: ALL protocol has a better clinical effect than AML protocol in children with ALAL, and positive MRD after induction therapy suggests poor prognosis. Hyperleukocytosis and adverse genetic changes are not observed in children with myeloid expression, and such children tend to have a good prognosis, suggesting that we should be cautious to take it as ALAL in diagnosis and treatment.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Criança , Intervalo Livre de Doença , Humanos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
4.
J Clin Lab Anal ; 35(8): e23896, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34237177

RESUMO

BACKGROUND: The aim of this study was to design and analyze the applicability of a 21-gene high-throughput sequencing (HTS) panel in the molecular diagnosis of patients with hereditary thrombocytopenia (HT). METHODS: A custom target enrichment library was designed to capture 21 genes known to be associated with HTs. Twenty-four patients with an HT phenotype were studied using this technology. RESULTS: One pathogenic variant on the MYH9 gene and one likely pathogenic variant on the ABCG8 gene previously known to cause HTs were identified. Additionally, 3 previously reported variants affecting WAS, ADAMTS13, and GP1BA were detected, and 9 novel variants affecting FLNA, ITGB3, NBEAL2, MYH9, VWF, and ANKRD26 genes were identified. The 12 variants were classified to be of uncertain significance. CONCLUSION: Our results demonstrate that HTS is an accurate and reliable method of pre-screening patients for variants in known HT-causing genes. With the advantage of distinguishing HT from immune thrombocytopenia, HTS could play a key role in improving the clinical management of patients.


Assuntos
Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Trombocitopenia/genética , Adolescente , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Trombocitopenia/etiologia
5.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(8): 828-833, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32800028

RESUMO

OBJECTIVE: To study the occurrence of serious adverse events (SAEs) related to chemotherapy with CCCG-ALL-2015 regimen in children with acute lymphoblastic leukemia (ALL) and the risk factors for death after the SAEs. METHODS: A retrospective analysis was performed on the medical data of 734 children with ALL. They were treated with CCCG-ALL-2015 regimen from January 2015 to June 2019. The occurrence of SAEs during the treatment was investigated. The children with SAEs were divided into a death group with 25 children and a survival group with 31 children. A multivariate logistic regression analysis was used to analyze the risk factors for death after the SAEs. RESULTS: Among the 734 children with ALL, 56 (7.6%) experienced SAEs (66 cases) after chemotherapy, among which 41 cases occurred in the stage of remission induction therapy. Of all 66 cases of SAEs, 46 (70%) were infection-related SAEs, including 25 cases of septic shock (38%), 20 cases of severe pneumonia (30%), and 1 case of severe chickenpox (2%), and 87% of the children with infection-related SAEs had neutrophil deficiency. The most common infection sites were blood and the lungs. The most common pathogens were Gram-negative bacteria, viruses, fungi, and Gram-positive bacteria. There were 16 cases (24%) of hemorrhage-related SAEs, with 11 cases of gastrointestinal bleeding (17%), 4 cases of pulmonary bleeding (6%), and 1 case of intracranial bleeding (2%). Of all 734 children with ALL, 66 (9.0%) died, among whom 25 died due to SAEs. The treatment-related mortality rate was 3.4%, and infection (72%) and bleeding (24%) were the main causes of death. Severe pneumonia was an independent risk factor for treatment-related death in ALL children (OR=4.087, 95%CI: 1.161-14.384, P=0.028). CONCLUSIONS: SAEs often occur in the stage of remission induction therapy, and infection-related SAEs are more common in ALL children accepting chemotherapy with CCCG-ALL-2015 regimen. The development of severe pneumonia suggests an increased risk for death in these children.


Assuntos
Antineoplásicos/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Bactérias Gram-Negativas , Humanos , Neutrófilos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco
6.
Medicine (Baltimore) ; 99(7): e19150, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049841

RESUMO

Chronic myeloid leukemia (CML) is relatively rare in childhood and few studies have reported the clinical use of imatinib (IM) in pediatric CML. In this study, we evaluated the efficacy and tolerability of IM in children and adolescents with CML.We investigated 21 patients under 18 years of age with newly diagnosed CML and treated with IM in Children's Hospital of Chongqing Medical University between May 2014 and February 2018. The disease was staged according to the European LeukemiaNet criteria and the IM dose was determined based on the disease stage. Cumulative responses and survival probabilities were estimated according to the Kaplan-Meier method.The estimated complete hematologic response rate of chronic phase-chronic myeloid leukemia (CML-CP) was 89.5% at 3 months. The complete cytogenetic response rates increased with time, reaching 47.4%, 73.7%, and 80.3% at 6, 12, and 24 months, respectively. The cumulative major molecular response rates were 42.1% and 76.3% at 12 and 24 months, respectively. With a median follow-up time of 33.8 months (range, 3.2-61.7 months), the estimated 2-year overall survival (OS) rate for CML was 95.2% (95% confidence interval [CI], 70.7%-99.3%). None of the CML-CP patients progressed to the accelerated phase or had a blast crisis. The 2-year OS and progression-free survival rates for the CML-CP cohort were both 100%, while the estimated 2-year event-free survival rate was 68% (95% CI, 42.1%-84.2%). None of the patients in this group had treatment-related deaths or IM discontinuation due to drug toxicities, and only 1 patient had a grade III-IV nonhematologic adverse event. Overall, anemia was the most common adverse effect and 42.9% of patients had a decrease in bone mineral density.IM was effective and the adverse effects were well-tolerated throughout the follow-up period in Chinese CML patients under 18 years of age.


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adolescente , Criança , China/epidemiologia , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Estudos Retrospectivos , Resultado do Tratamento
7.
Int J Lab Hematol ; 41(2): 234-241, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30624855

RESUMO

INTRODUCTION: To investigate the correlation of long noncoding RNA-SOX6-1 (lnc-SOX6-1) with clinicopathological features and treatment outcomes in pediatric acute myeloid leukemia (AML) patients, and further explore its function in AML cell proliferation and apoptosis. METHODS: A total of 146 de novo pediatric AML patients and 73 nonhematologic malignancy patients/donors were recruited. Bone marrow samples were obtained, followed by measurement of lnc-SOX6-1 expression by qPCR. Besides, lnc-SOX6-1 expression in various AML cells and control cells was detected. Blank overexpression (NC (+)), lnc-SOX6-1 overexpression (Lnc RNA (+)), blank shRNA (NC (-)), and lnc-SOX6-1 shRNA plasmids (Lnc RNA (-)) were transferred into KG-1 cells and THP-1 cells. Cell proliferation rate and cell apoptosis rate were detected by CCK-8 assay and AV/PI assay, respectively. RESULTS: Lnc-SOX6-1 expression was upregulated in pediatric AML patients compared to controls, and its high expression correlated with the presence of monosomal karyotype, severer risk stratification, lower possibility of complete response achievement, shorter event-free survival, and poor overall survival. Furthermore, lnc-SOX6-1 expression was elevated in various AML cells compared to normal cells. In KG-1 cells and THP-1 cells, cell proliferation rate was elevated in Lnc RNA (+) group but reduced in Lnc RNA (-) group at 48 and 72 hours, and cell apoptosis rate was decreased in Lnc RNA (+) group but increased in Lnc RNA (-) group at 72 hours compared to the corresponding control groups. CONCLUSION: Lnc-SOX6-1 is highly expressed and correlates with worse risk stratification and poor treatment outcomes, and promotes cell proliferation while represses apoptosis in pediatric AML.


Assuntos
Apoptose , Proliferação de Células , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Regulação para Cima , Criança , Pré-Escolar , Feminino , Células HL-60 , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Estudos Prospectivos , Fatores de Risco , Células THP-1
8.
Oncol Lett ; 15(4): 4314-4322, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29541198

RESUMO

Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is closely associated with a number of diseases; however, its influence in B-cell acute lymphoblastic leukemia (B-ALL) and the potential molecular mechanisms involved remain unclear. The present study aimed to evaluate the expression of PRPS1 in Chinese children with B-ALL and to investigate the mechanism of action of PRPS1 in this disease. A Cell Counting Kit-8 (CCK-8) assay was performed to examine the proliferation of B-ALL Sup-B15 and Raji cells, and flow cytometric analysis was conducted to determine the cell cycle distribution and rate of apoptosis. The mRNA and protein expression levels of PRPS1, MYC proto-oncogene, bHLH transcription factor, cyclin E1, B-cell lymphoma-2 (Bcl-2), cyclin dependent kinase 2 and caspase-3 were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Elevated PRPS1 expression was associated with a high-risk stratification and poor prognosis in patients with B-ALL. Furthermore, overexpression of PRPS1 accelerated the growth of and inhibited apoptosis in Sup-B15 and Raji cells as well as increasing the expression of Bcl-2 to induce an anti-apoptotic effect in B-ALL cell lines. The results of the present study indicate that PRPS1 regulates multiple processes in B-ALL and may be an attractive therapeutic target.

9.
Semin Thromb Hemost ; 43(6): 629-634, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28444667

RESUMO

This study aims to determine the clinical significance of positive antinuclear/antiextractable nuclear antigen (ANA/A-ENA) antibody on manifestation and therapeutic response of childhood immune thrombocytopenia (ITP). Overall, 1,330 patients aged between 1 and 15.6 years diagnosed with primary ITP were retrospectively analyzed, excluding those with secondary ITP. Bleeding manifestations were recorded. All patients underwent autoantibody testing and follow-up for 32 months on average (range: 23-54 months). Steroid response was also assessed. Response rates were compared between ANA/A-ENA-positive and ANA/A-ENA-negative patients. Of all the patients enrolled, 84 tested positive only for ANA, 102 tested positive for A-ENA, 54 tested positive for both ANA and A-ENA, and 1,090 tested negative for both. Patients who were ANA/A-ENA positive were more likely to be female and older than 10 years. Patients who were A-ENA positive were more likely to have either persistent or chronic disease and suffer from life-threatening bleeding as well as poor short-term therapeutic response. We conclude that autoantibody testing is important to determine the short-term prognosis of ITP patients. Females, patients older than 10 years of age, and patients with either mixed positivity or A-ENA positivity should be more closely monitored.


Assuntos
Anticorpos Antinucleares/sangue , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Estudos Retrospectivos , Globulina de Ligação a Hormônio Sexual , Esteroides/administração & dosagem
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(3): 433-6, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-27063178

RESUMO

OBJECTIVE: To summarize the clinical characteristics, laboratory findings and prognosis of patients with Down syndrome-related acute leukemia (DS-AL). METHODS: The clinical data, laboratory findings, chemotherapy and prognosis of 21 children with DS-AL were analyzed. RESULTS: Most of the children had disease onset of leukemia at 1 to 5 years of age (85.7%), and acute myeloid leukemia accounted for 57.1% of these cases; 61.9% of the patients had increased lactate dehydrogenase level by 2 folds or more. Of the 13 cases undergoing echocardiaography, 10 (67.9%) showed abnormal findings, and complex congenital heart disease was common (38.5%). Six of the children received chemotherapy and complete remission was achieved in 4 cases; 2 patients died of infection, and the treatment-related mortality was 33.3%. The 2 patients receiving reduced intensive chemotherapy have so far had event-free survival for 21 and 43 months. CONCLUSION: Acute myeloid leukemia is the most common subtype of DS-AL. Patients with DS-AL are sensitive to chemotherapy and the prognosis was favorable with reduced intensive chemotherapy.


Assuntos
Síndrome de Down/complicações , Leucemia Mieloide Aguda/complicações , Protocolos de Quimioterapia Combinada Antineoplásica , Pré-Escolar , Intervalo Livre de Doença , Humanos , Lactente , Leucemia Mieloide Aguda/tratamento farmacológico , Prognóstico , Indução de Remissão
11.
Nan Fang Yi Ke Da Xue Xue Bao ; 35(12): 1745-50, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-26714909

RESUMO

OBJECTIVE: To explore the clinical features, laboratory findings and treatment of infant leukemia. METHODS: A retrospective analysis of the clinical data was performed of the cases with the diagnosis of infant acute leukemia from August 1993 to October 2014 in our hospital. RESULTS: A total of 144 cases of infant leukemia were diagnosed in the defined period, including 83 cases of acute lymphoblastic leukemia, 55 myeloid leukemia, 1 hybrid acute leukaemia and 5 with incompatible cytological and immunophenotyping findings. The patients at the age of 9 to 12 months accounted for the largest proportion (38.2%), and 87.5% of the patients had hepatosplenomegaly; Six patients below 6 months old had skin infiltration. In about 1/3 of the patients, the white blood cells count was no greater than 100 × 109 /L. Ninety-five patients had chromosome examinations, which identified chromosome abnormalities in 67 patients, including 18 positive for t(4;11)or t(9;11)or t(11;19), and younger patients were more likely to have chromosome abnormalities. Thirty-seven patients underwent MLL gene detection and 11 of them had positive results; the positive patients had higher rate of chromosome 11 abnormalities than the negative patients. Most of the patients gave up treatments after diagnosis and only 6 patients older than 6 months completed regular chemotherapeutic treatments and were now in complete remission. CONCLUSION: Infant leukemia is a rare type of leukemia with different clinical features from other types of leukemia. The patients often present with hepatosplenomegaly, high white blood cell counts, MLL gene fusion, and chromosome 11 abnormalities. The prognosis of infant leukemia is not favorable, and the current treatment still relies on chemotherapy.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 11 , Leucemia Mieloide/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Doença Aguda , Transtornos Cromossômicos , Humanos , Imunofenotipagem , Lactente , Contagem de Leucócitos , Prognóstico , Estudos Retrospectivos
13.
Zhonghua Xue Ye Xue Za Zhi ; 35(5): 424-7, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-24857213

RESUMO

OBJECTIVE: To explore the risk factors, and control measures of cytomegalovirus (CMV) infection after hematopoietic stem cell transplantion (HSCT) in children with primary immunodeficiency diseases(PID). METHODS: We retrospectively analyzed results of 26 patients with PID-Wiskott-Aldrich syndrome (WAS, n=20), severe combined immunodeficiency (SCID, n=1) , X-linked chronic granulomatous disease (XCGD, n=2) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n=3)-who underwent HSCT from June 2007 to December 2012 in our center. Serologic studies (ELISA) and weekly CMV infection surveillance (quantitative PCR, qPCR) were routinely performed before and after HSCT. Ganciclovir or forcarnet was used for pre-emptive and curative therapy. RESULTS: All 26 patients were male with the median age at HSCT of 27 months (range 7-77 months). At a median follow up of 24 months (range 5-66 months), the 5-year overall survival rate was (75.0 ± 9.0) %. CMV infection occurred in 42.3% (11 of 26) of the patients, two of them developed CMV interstitial pneumonia (CMVIP). Univariate analysis revealed that the incidence of pre-transplant CMV infection between with and without CMV activation groups after HSCT was significantly different (62.5% vs 10.0%, P=0.010). Additional variables not associated with CMV infection were stem-cell sources, donor type, HLA disparity and acute GVHD (all P values>0.05). CONCLUSION: CMV infection was a major complication of HSCT. Sensitive monitoring, early diagnosis, timely treatment may improve the survival rate for these PID undergoing HSCT.


Assuntos
Infecções por Citomegalovirus/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Criança , Pré-Escolar , Doença Enxerto-Hospedeiro , Doença Granulomatosa Crônica/terapia , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , Imunodeficiência Combinada Severa/terapia , Doadores de Tecidos , Síndrome de Wiskott-Aldrich/terapia
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 15(9): 737-42, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24034915

RESUMO

OBJECTIVE: The Chinese Children's Leukemia Group (CCLG)-acute lymphoblastic leukemia (ALL) 08 protocol for childhood ALL was established in 2008. This study aims to evaluate the drug-related toxicities of CCLG-ALL 08 protocol in the treatment of childhood ALL. METHODS: A total of 114 children with newly diagnosed ALL were treated with the CCLG-ALL 08 protocol. The protocol was divided into five phases: remission induction (VDLD), early reinforcement (CAM), consolidation therapy, delayed reinforcement (DIa & DIb) and maintenance treatment. Drug-related toxicities in each phase were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Toxicities were more frequent in phase VDLD than other treatment phases, including hepatotoxicity (87.7%), dental ulcer (20.2%), hyperglycemia (20.2%), prolonged activated partial thromboplastin time (21.1%) and decreased fibrinogen (34.2%), with the incidence rates of severe adverse events at 7%, 0, 1.3%, 0.8% and 2.7% respectively. The incidence of allergic reaction to L-ASP was significantly higher in phase DIa than in phase VDLD (28.0% vs 7.9%; P<0.01), and there were no longer any allergic reactions in 15 patients who received continuing treatment with pegaspargase instead. There was no severe arrhythmia, myocardial ischemia, decreased left ventricular function, osteonecrosis, myopathy, organ failure or treatment-related mortality. CONCLUSIONS: The drug-related toxicities of CCLG-ALL 08 protocol are common in phase VDLD, but they are mild and reversible. There is no treatment-related mortality. The CCLG-ALL 08 protocol for childhood ALL is safe.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Asparaginase/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Indução de Remissão
16.
Zhonghua Er Ke Za Zhi ; 48(8): 629-32, 2010 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21055312

RESUMO

OBJECTIVE: To summarize the clinical characteristics of secondary coagulation disorders caused by exposure to poison (raticide) in children and to investigate the diagnosis and corresponding treatment. METHOD: The process of diagnosis, clinical characteristics, response to treatment and the prognosis were analyzed. RESULTS: The main clinical manifestation was mucosal bleeding (66.6%), including epistaxis, gingival bleeding, hematomas and so on. All these children were previously well and had no history of bleeding. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged, factor II was undetectable and the levels of factors VII, IX, and X were lower. The fibrinogen was normal. A raticide was detected in blood and urine of 13 children although 12 of the patients had no definite history of raticide ingestion. Prothrombin complex, fresh frozen plasma and vitamin K(1) were effective in these cases. However, 2 - 3 weeks later, 6 patients presented with recurrent bleeding. CONCLUSION: For children with secondary coagulation disorders of unknown cause, intoxication of raticide should be considered. The administration of blood coagulation factors and vitamin K(1) are effective in early treatment, and the treatment period should be more than 2 months. The PT and APTT should be followed up. Vitamin K(1) should be stopped when PT and APTT are normal.


Assuntos
Transtornos da Coagulação Sanguínea/induzido quimicamente , Transtornos da Coagulação Sanguínea/terapia , Rodenticidas/envenenamento , Vitamina K 1/uso terapêutico , Transtornos da Coagulação Sanguínea/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Vitamina K 1/administração & dosagem
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 39(6): 905-8, 2008 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-19253822

RESUMO

OBJECTIVE: To study the effect of Survivin antisense oligodeoxgnucleotide (ASODN) on drug resistance and its mechanism in K562 cells. METHODS: Cells were divided into four groups: ASODN group, SODN group, Lip group and blank group. Survivin ASODN was transfered into K562 cells by liposomal reagent. The expression of Survivin mRNA was detected by RT-PCR. The sensitivity of K562 cells to adriamycin (ADM) and daunorubicin (DAM) was detected by MTT assay, while the intracellular concentration of ADM and DAM was measured by flowcytometry. RESULTS: Compared to control group Survivin mRNA expression in ASODN group decreased obviously. IC50(s) of ADM and ASODN+ADM were 0.5457 mg/L and 0.1933 mg/L respectively, IC50 (s) of DAM and ASODN+DAM were 0.5408 mg/L and 0.2027 mg/L respectively. Expression of Survivin mRNA decreased by 25.8% after the transfection of ASODN. Fluorescence intensity of ADM and ASODN+ADM in K562 cells were 51.64 and 89.92, Fluorescence intensity of DAM and ASODN+DAM in K562 cells were 63.71 and 88.47. CONCLUSION: Expression of Survivin mRNA in k562 cells was down-regulated by ASODN. Survivin ASODN is able to reverse the drug resistance via inhibition of Survivin expression and inducement of apoptosis.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/genética , Oligodesoxirribonucleotídeos Antissenso/farmacologia , Daunorrubicina/farmacologia , Doxorrubicina/farmacologia , Humanos , Proteínas Inibidoras de Apoptose , Células K562 , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/farmacologia , Oligodesoxirribonucleotídeos Antissenso/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Survivina
18.
Zhonghua Er Ke Za Zhi ; 43(4): 279-83, 2005 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-15924721

RESUMO

OBJECTIVE: Gene therapy of leukemia is a new and effective method. It is known to all that the pathogenesis and development of leukemia are related to a variety of genes. Survivin is a member of inhibitors of apoptotic proteins (IAP). Its cDNA was cloned from target cell protease receptor-1 (EPR-1). It is expressed in common tumors, but there is no expression in normal and mature tissues. High expression of survivin was detected in leukemic cells. The present study was conducted to examine the role of survivin in the differentiation of leukemic cells by using antisense-oligonucleotides. METHODS: Human leukemic cell K562 was used as the model for the study. K562 cells were divided into 4 groups randomly: antisense oligonucleuotide (ASON) group, nonsense oligonucleotide (NSON) group, lipofectin group and control group. There were 5 samples in each group, and the experiment was repeated for three times. ASON was designed with the reference to targeting survivin mRNA. K562 cells were cultured in RPMI1640 contained fetal cattle serum at a concentration of about 10 percent. Cell transfection was induced by lipofectin. Forty-eight hours after thansfection, the morphology and ultrastructure were observed. Twenty-four hours and 48 hours after thansfection, the function of K562 cells was detected by benzidine staining, POX staining and NBT staining, respectively. The mean fluorescence intensity of CD33 was determined by flow cytometry. The method of immunohistochemistry was used to examine the protein level of survivin. RESULTS: After thansfection with ASON, the size of K562 cells was reduced, but the cytoplasm was increased. The metarubricyte, segment granulocyte, apoptotic cells could be found. Morphologically and ultrastructurally, erythroid and myelocytic differentiation was observed. The positive level of benzidine staining in ASON group (11.90 +/- 2.30 at 24 h and 18.20 +/- 2.93 at 48 h) was higher than that of NSON group, lipofectin group and control group, respectively. The positive level of POX staining in ASON group (17.40 +/- 3.54 at 24 h and 29.40 +/- 3.70 at 48 h) was also higher than that of any other groups. The positive level of NBT staining in ASON group (7.50 +/- 2.26 at 24 h and 12.10 +/- 2.63 at 48 h) was significantly higher than that of NSON group, lipofectin group and control group, respectively (P < 0.01). In ASON group, the mean fluorescence intensity of CD33 (21.43 +/- 1.61 at 24 h and 14.86 +/- 1.20 at 48 h) was significantly lower than that of any other groups (P < 0.01). After thansfection for 24 h, the protein level of survivin in ASON group was decreased significantly compared to that of control group. There was no difference in survivin protein level amongst ASON group, NSON group and lipofectin group at 24 h (P > 0.05). Forty-eight hours after thansfection, the protein level of survivin was decreased significantly. CONCLUSIONS: ASON targeting survivin can induce K562 to erythroid and myelocytic differentiation. Survivin is related to differentiation of K562 cells, and it can be a target of gene therapy for leukemia.


Assuntos
Proteínas Associadas aos Microtúbulos/fisiologia , Oligonucleotídeos Antissenso/genética , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Diferenciação Celular , Humanos , Proteínas Inibidoras de Apoptose , Células K562 , Proteínas Associadas aos Microtúbulos/análise , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos/genética , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico , Survivina , Transfecção
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