The efficiency of dendritic cell-activated and cytokine-induced killer cell（DC-CIK） therapy on children with acute myeloid leukemia（AML） after chemotherapy was investigated. Mononuclear cells were collected from c...The efficiency of dendritic cell-activated and cytokine-induced killer cell（DC-CIK） therapy on children with acute myeloid leukemia（AML） after chemotherapy was investigated. Mononuclear cells were collected from children achieving complete remission after chemotherapy,cultured in vitro and transfused back into the same patient. Interleukin-2（IL-2） was injected subcutaneously every other day 10 times at the dose of 1×106 units. Peripheral blood lymphocyte subsets and minimal residual disease（MRD） were detected by flow cytometry. Function of bone marrow was monitored by methods of morphology,immunology,cytogenetics and molecular biology. The side effects were also observed during the treatment. The average follow-up period for all the 22 patients was 71 months and relapse occurred in two AML patients（9.1%）. The percentage of CD3＋/CD8＋ cells in peripheral blood of 15 patients at the 3rd month after DC-CIK treatment（36.73%±12.51%） was dramatically higher than that before treatment（29.20%±8.34%,P〈0.05）. The MRD rate was 〉0.1% in 5 patients before the treatment,and became lower than 0.1% 3 months after the treatment. During the transfusion of DC-CIK,side effects including fever,chills and hives appeared in 7 out of 22（31.82%） cases but disappeared quickly after symptomatic treatments. There were no changes in electrocardiography and liver-renal functions after the treatment. MRD in children with AML can be eliminated by DC-CIK therapy which is safe and has fewer side effects.展开更多
Objective： Multidrug resistance（MDR） is one of the most important reasons for treatment failure and recurrence of acute leukemia. Its manifestations are different in children with acute lymphoblastic leukemia（ALL...Objective： Multidrug resistance（MDR） is one of the most important reasons for treatment failure and recurrence of acute leukemia. Its manifestations are different in children with acute lymphoblastic leukemia（ALL） which may be due to different detection methods. This study was to detect the expression of MDR1 mRNA in bone marrow cells of children with ALL by real-time fluorescence- quantitative reverse transcription polymerase-chain reaction（FQ-RT-PCR）, and combine minimal residual desease（MRD） detection by flow cytometry（FCM） and to study their relationship with treatment response and prognosis of ALL. Methods：The MDR1 mRNA levels in bone marrow cells from 67 children with ALL[28 had newly diagnosed disease, 27 had achieved complete remission（CR）, 12 recurrent] and 22 children without leukemia were detected by FQ-RT-PCR. MRD was detected by FCM. The patients were observed for 9-101 months, with a median of 64 months. Results：Standard curves of human MDR1 and GAPDH genes were constructed successfully. MDR1 mRNA was detected in all children with a positive rate of 100%. The mRNA level of MDR1 was similar among the newly diagnosed ALL group, CR group, and control group（P 〉 0.05）, but significantly higher in the recurrence group than that in newly diagnosed disease group and control group（0.50 ± 0.55 vs. 0.09 ± 0.26 and 0.12 ± 0.23, P〈 0.05）. 54 ALL patients were followed up, and it was found that MDR1 mRNA level was significantly higher in ALL patients within 3 years duration than that of ALL patients with 3-6 years and over 6 years duration（0.63 ± 0.56 vs. 0.11 ± 0.12 and 0.04 ± 0.06, P〈 0.01）. For the 28 children with newly diagnosed disease, the MDR1 mRNA level was similar between WBC 〉 50 ~ 109 group and WBC〈50 × 10^9 group（P〉 0.05）. In the 33 CR patients, the MDR1 mRNA level was significantly higher in MRD〉10a group than that in MRD〈10a group（0.39 ± 0.47 vs. 0.03 ± 0.03, P 〈 0.05）. Conclusion：The sensitivity and specificity of FQ-RT-PCR in detecting MDR1 mRNA in bone marrowy cells of children with ALL patients are high. MDR1 mRNA is expressed in children with and without leukemia. MDR1 mRNA is highly expressed in the CR ALL patients with high MRD, recurrence and short duration（within 3 years）. Monitoring MRD and the MDR1 mRNA level might be helpful for individual treatment.展开更多
Background: In recent decades, the incidence of children’s hematological malignancies has been increasing worldwide including Tunisia. Their severity is reflected in the importance of the medical, social and economic...Background: In recent decades, the incidence of children’s hematological malignancies has been increasing worldwide including Tunisia. Their severity is reflected in the importance of the medical, social and economic impact. This increase remains fully unexplained, and the involvement of genetic, environmental and occupational factors is strongly suspected. Materials and methods: Our study was a cross-sectional survey of the type case-control conducted in the University Hospital of Farhat Hached of Sousse during the period ranging between 1 July 2011 and 30 June 2012, and which included children with acute leukemia compared to children unharmed by neoplastic disease. Cases and controls were matched by age and gender. Our objective was to describe the socio-occupational characteristics of the parents of children with acute leukemia and to identify potential occupational factors implicated in the genesis of acute leukemia. Results: The number of acute leukemia cases in the Hematology Service and day hospital of the University Hospital of Farhat Hached during the study period was 66 cases divided into in 40 boys and 26 girls with a sex ratio of 1.53. Our cases and controls were matched by age and gender. The risk of incidence of leukemia in children from smoking fathers was higher (p = 0.02, OR = 2.24, IC = [1.11 - 4.52]). The risk of incidence of leukemia in children from alcoholic fathers was higher with p = 0.009, OR = 3.9;CI = [1.33 - 11.39]. After adjusting different variables, the difference persisted significantly with pa = 0.03 and ORa = 3.5, ICa = [1.09 - 11.6]. 25.7% of cases had a family history of blood disease and neoplasia, whereas no control presented that. The difference was statistically significant (p = 0.006, OR = 1.46, IC = [1.38 - 1.56]). The parental occupational exposures associated to the occurrence of acute leukemia in children were pesticides with a statistically significant difference (p = 0.03, OR = 2.94, IC = [1.06 - 8.13]). This difference persisted after adjustment with different variables pa = 0.01, ORa 3.75;ICa = [1.27 - 11.03]. This difference had become significant after adjustment with the different variables pa = 0.03, ORa = 2.67, ICa = [1.06 - 6.7]. Conclusion: Our results showed some support for a positive association between childhood acute leukemia risk and parental occupational exposure to pesticides and cement. Additionally, acute leukemia risk among children might be increased with parental alcohol consumption.展开更多
Background: In Mexico, AML survival is referred in 30%. Our aim was to evaluate results with ADE protocol as induction treatment in children with non-M3 AML in a public Mexican institution. Method: We included patient...Background: In Mexico, AML survival is referred in 30%. Our aim was to evaluate results with ADE protocol as induction treatment in children with non-M3 AML in a public Mexican institution. Method: We included patients with AML in a single institution between 2005 and 2013. All non-M3-AML patients received ADE as induction therapy (cytarabine 100 mg/m<sup>2</sup> in continuous infusion from day 1 to 7, daunorrubicin 30 mg/m<sup>2</sup> days 1, 3, 5 and etoposide 100 mg/m<sup>2</sup> over days 1 to 5). Patients received antibiotic prophylaxis and strict scheduled appointments to assure adherence and prevent avoidable emergencies. Main Results: Eighteen patients were included. Median age was 106 months. One patient died at diagnosis so 17 were eligible for induction results analysis;eleven needed two cycles and six patients three. Remission rate was 100%. Analyzing non-M3 patients overall survival was 80.2% at 100 months. No fatal complications were observed. Stratifying by number of cycles we observe that patients receiving one ADE cycle had a 0% overall survival at short follow up, with 2 ADE cycles 80% at 100 months and with 3 cycles 100% at 60 months. Conclusion: ADE induction therapy showed improved results in overall survival compared with other standard regimens. Following the protocol we obtained 100% remission. This is an important achievement in our population. Our focus must be to ameliorate maintenance final results. These results should be reproduced in other hospitals in Mexico and other countries.展开更多
目的分析儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)经中国儿童肿瘤协作组急性淋巴细胞白血病2015方案(Chinese Children's Cancer Group ALL-2015 protocol,CCCG-ALL-2015)治疗后的累积复发率(cumulative incidenc...目的分析儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)经中国儿童肿瘤协作组急性淋巴细胞白血病2015方案(Chinese Children's Cancer Group ALL-2015 protocol,CCCG-ALL-2015)治疗后的累积复发率(cumulative incidence of relapse,CIR),并探讨影响复发的危险因素。方法回顾性分析2015年1月—2019年12月接受CCCG-ALL-2015方案治疗的852例患儿的临床资料,计算CIR并分析影响儿童急性B淋巴细胞白血病(B-ALL)复发的危险因素。结果852例ALL患儿中,146例(17.1%)发生复发,8年CIR为(19.8±1.6)%。B-ALL与急性T淋巴细胞白血病患儿的8年CIR比较差异无统计学意义(P>0.05)。146例复发患儿中,复发时间主要集中于极早期(62例,42.5%)和早期(46例,31.5%),极早期单纯骨髓复发42例(28.8%),早期单纯骨髓复发27例(18.5%)。Cox比例风险回归模型分析显示,融合基因MLLr阳性(HR=4.177,95%CI:2.086~8.364,P<0.001)和第46天微小残留病≥0.01%(HR=2.013,95%CI:1.163~3.483,P=0.012)是B-ALL患儿经CCCG-ALL-2015方案治疗后复发的危险因素。结论儿童ALL经CCCG-ALL-2015方案治疗后仍有较高的复发率,以极早期和早期单纯骨髓复发常见;第46天微小残留病≥0.01%、融合基因MLLr阳性与B-ALL复发密切相关。展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81000211)Important Research Project from Health Department of Hubei Province,China(No.JX4A05)
文摘The efficiency of dendritic cell-activated and cytokine-induced killer cell（DC-CIK） therapy on children with acute myeloid leukemia（AML） after chemotherapy was investigated. Mononuclear cells were collected from children achieving complete remission after chemotherapy,cultured in vitro and transfused back into the same patient. Interleukin-2（IL-2） was injected subcutaneously every other day 10 times at the dose of 1×106 units. Peripheral blood lymphocyte subsets and minimal residual disease（MRD） were detected by flow cytometry. Function of bone marrow was monitored by methods of morphology,immunology,cytogenetics and molecular biology. The side effects were also observed during the treatment. The average follow-up period for all the 22 patients was 71 months and relapse occurred in two AML patients（9.1%）. The percentage of CD3＋/CD8＋ cells in peripheral blood of 15 patients at the 3rd month after DC-CIK treatment（36.73%±12.51%） was dramatically higher than that before treatment（29.20%±8.34%,P〈0.05）. The MRD rate was 〉0.1% in 5 patients before the treatment,and became lower than 0.1% 3 months after the treatment. During the transfusion of DC-CIK,side effects including fever,chills and hives appeared in 7 out of 22（31.82%） cases but disappeared quickly after symptomatic treatments. There were no changes in electrocardiography and liver-renal functions after the treatment. MRD in children with AML can be eliminated by DC-CIK therapy which is safe and has fewer side effects.
基金This work was supported by Science Project from Science and Tech- nology Department of HuBei province(2006AA301B56-3)
文摘Objective： Multidrug resistance（MDR） is one of the most important reasons for treatment failure and recurrence of acute leukemia. Its manifestations are different in children with acute lymphoblastic leukemia（ALL） which may be due to different detection methods. This study was to detect the expression of MDR1 mRNA in bone marrow cells of children with ALL by real-time fluorescence- quantitative reverse transcription polymerase-chain reaction（FQ-RT-PCR）, and combine minimal residual desease（MRD） detection by flow cytometry（FCM） and to study their relationship with treatment response and prognosis of ALL. Methods：The MDR1 mRNA levels in bone marrow cells from 67 children with ALL[28 had newly diagnosed disease, 27 had achieved complete remission（CR）, 12 recurrent] and 22 children without leukemia were detected by FQ-RT-PCR. MRD was detected by FCM. The patients were observed for 9-101 months, with a median of 64 months. Results：Standard curves of human MDR1 and GAPDH genes were constructed successfully. MDR1 mRNA was detected in all children with a positive rate of 100%. The mRNA level of MDR1 was similar among the newly diagnosed ALL group, CR group, and control group（P 〉 0.05）, but significantly higher in the recurrence group than that in newly diagnosed disease group and control group（0.50 ± 0.55 vs. 0.09 ± 0.26 and 0.12 ± 0.23, P〈 0.05）. 54 ALL patients were followed up, and it was found that MDR1 mRNA level was significantly higher in ALL patients within 3 years duration than that of ALL patients with 3-6 years and over 6 years duration（0.63 ± 0.56 vs. 0.11 ± 0.12 and 0.04 ± 0.06, P〈 0.01）. For the 28 children with newly diagnosed disease, the MDR1 mRNA level was similar between WBC 〉 50 ~ 109 group and WBC〈50 × 10^9 group（P〉 0.05）. In the 33 CR patients, the MDR1 mRNA level was significantly higher in MRD〉10a group than that in MRD〈10a group（0.39 ± 0.47 vs. 0.03 ± 0.03, P 〈 0.05）. Conclusion：The sensitivity and specificity of FQ-RT-PCR in detecting MDR1 mRNA in bone marrowy cells of children with ALL patients are high. MDR1 mRNA is expressed in children with and without leukemia. MDR1 mRNA is highly expressed in the CR ALL patients with high MRD, recurrence and short duration（within 3 years）. Monitoring MRD and the MDR1 mRNA level might be helpful for individual treatment.
文摘Background: In recent decades, the incidence of children’s hematological malignancies has been increasing worldwide including Tunisia. Their severity is reflected in the importance of the medical, social and economic impact. This increase remains fully unexplained, and the involvement of genetic, environmental and occupational factors is strongly suspected. Materials and methods: Our study was a cross-sectional survey of the type case-control conducted in the University Hospital of Farhat Hached of Sousse during the period ranging between 1 July 2011 and 30 June 2012, and which included children with acute leukemia compared to children unharmed by neoplastic disease. Cases and controls were matched by age and gender. Our objective was to describe the socio-occupational characteristics of the parents of children with acute leukemia and to identify potential occupational factors implicated in the genesis of acute leukemia. Results: The number of acute leukemia cases in the Hematology Service and day hospital of the University Hospital of Farhat Hached during the study period was 66 cases divided into in 40 boys and 26 girls with a sex ratio of 1.53. Our cases and controls were matched by age and gender. The risk of incidence of leukemia in children from smoking fathers was higher (p = 0.02, OR = 2.24, IC = [1.11 - 4.52]). The risk of incidence of leukemia in children from alcoholic fathers was higher with p = 0.009, OR = 3.9;CI = [1.33 - 11.39]. After adjusting different variables, the difference persisted significantly with pa = 0.03 and ORa = 3.5, ICa = [1.09 - 11.6]. 25.7% of cases had a family history of blood disease and neoplasia, whereas no control presented that. The difference was statistically significant (p = 0.006, OR = 1.46, IC = [1.38 - 1.56]). The parental occupational exposures associated to the occurrence of acute leukemia in children were pesticides with a statistically significant difference (p = 0.03, OR = 2.94, IC = [1.06 - 8.13]). This difference persisted after adjustment with different variables pa = 0.01, ORa 3.75;ICa = [1.27 - 11.03]. This difference had become significant after adjustment with the different variables pa = 0.03, ORa = 2.67, ICa = [1.06 - 6.7]. Conclusion: Our results showed some support for a positive association between childhood acute leukemia risk and parental occupational exposure to pesticides and cement. Additionally, acute leukemia risk among children might be increased with parental alcohol consumption.
文摘Background: In Mexico, AML survival is referred in 30%. Our aim was to evaluate results with ADE protocol as induction treatment in children with non-M3 AML in a public Mexican institution. Method: We included patients with AML in a single institution between 2005 and 2013. All non-M3-AML patients received ADE as induction therapy (cytarabine 100 mg/m<sup>2</sup> in continuous infusion from day 1 to 7, daunorrubicin 30 mg/m<sup>2</sup> days 1, 3, 5 and etoposide 100 mg/m<sup>2</sup> over days 1 to 5). Patients received antibiotic prophylaxis and strict scheduled appointments to assure adherence and prevent avoidable emergencies. Main Results: Eighteen patients were included. Median age was 106 months. One patient died at diagnosis so 17 were eligible for induction results analysis;eleven needed two cycles and six patients three. Remission rate was 100%. Analyzing non-M3 patients overall survival was 80.2% at 100 months. No fatal complications were observed. Stratifying by number of cycles we observe that patients receiving one ADE cycle had a 0% overall survival at short follow up, with 2 ADE cycles 80% at 100 months and with 3 cycles 100% at 60 months. Conclusion: ADE induction therapy showed improved results in overall survival compared with other standard regimens. Following the protocol we obtained 100% remission. This is an important achievement in our population. Our focus must be to ameliorate maintenance final results. These results should be reproduced in other hospitals in Mexico and other countries.
文摘目的分析儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)经中国儿童肿瘤协作组急性淋巴细胞白血病2015方案(Chinese Children's Cancer Group ALL-2015 protocol,CCCG-ALL-2015)治疗后的累积复发率(cumulative incidence of relapse,CIR),并探讨影响复发的危险因素。方法回顾性分析2015年1月—2019年12月接受CCCG-ALL-2015方案治疗的852例患儿的临床资料,计算CIR并分析影响儿童急性B淋巴细胞白血病(B-ALL)复发的危险因素。结果852例ALL患儿中,146例(17.1%)发生复发,8年CIR为(19.8±1.6)%。B-ALL与急性T淋巴细胞白血病患儿的8年CIR比较差异无统计学意义(P>0.05)。146例复发患儿中,复发时间主要集中于极早期(62例,42.5%)和早期(46例,31.5%),极早期单纯骨髓复发42例(28.8%),早期单纯骨髓复发27例(18.5%)。Cox比例风险回归模型分析显示,融合基因MLLr阳性(HR=4.177,95%CI:2.086~8.364,P<0.001)和第46天微小残留病≥0.01%(HR=2.013,95%CI:1.163~3.483,P=0.012)是B-ALL患儿经CCCG-ALL-2015方案治疗后复发的危险因素。结论儿童ALL经CCCG-ALL-2015方案治疗后仍有较高的复发率,以极早期和早期单纯骨髓复发常见;第46天微小残留病≥0.01%、融合基因MLLr阳性与B-ALL复发密切相关。
