Background: The treatment used to combat acute lymphoblastic leukemia (ALL) is multidrug;therefore it is important to use active pharmacovigilance to detect, assess and analyze the likely adverse reactions which may o...Background: The treatment used to combat acute lymphoblastic leukemia (ALL) is multidrug;therefore it is important to use active pharmacovigilance to detect, assess and analyze the likely adverse reactions which may occur during the same period. Objective: To determine the frequency of adverse reactions to chemotherapeutic drugs in children with ALL. Material and Methods: Intensive pharmacovigilance was used to record the reports of adverse reactions to vincristine, L-asparaginase and the vincristine-L-asparaginase combination in children with ALL in a paediatric hospital. For each notification, the adverse reactions were analyzed in order to verify causality. Results: Forty patients were evaluated. Twenty children were female (50.0%) and 20 were male (50%). The children had a mean age, weight and height (±standard deviation: SD) of 8.1 (±3.4) years, 31.4 (±13.9) kg and 1.3 (±0.2) m, respectively. Vincristine was administered to 19 patients, vincristine plus L-asparaginase were given to 19 patients and only 2 patients used L-asparaginase. One-hundred-ninety adverse reactions were detected in the patients, with an average (±SD) of 4.8 (±2.6). Ondansetron was the drug administered for the treating of nausea and vomiting. One hundred eighty-one (95.3%) adverse reactions were identified as “definite”, 5 (2.6%) as “probable” and 4 (2.1%) as “doubtful”. Conclusions: There is a high incidence of adverse reactions by the administration of vincristine and L-asparaginase;the reactions of highest incidence were: nausea, vomiting, neutropenia, diarrhea, constipation, mucositis, headache, and abdominal pain. It is important to promote the detection, collection, reporting, assessment and treatment of ARD’s in children. It is necessary to promote the conduct further studies on pharmacovigilance with this type of treatments and to increase the duration of the studies.展开更多
Objective:To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia cells....Objective:To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia cells.Methods:Acute lymphoblastic leukemia cells REH and CCRFCEM were employed to detect the anti-tumor effect of vincristine and doxorubicin on proliferation and apoptosis using EdU assay,human active caspase-3 Quantikine ELISA kit,and flow cytometry.Vincristine-resistant REH cells(REH-R),survivin knockdown and overexpressing REH cells were established to verify the role of survivin in drug resistance.Additionally,in vitro and in vivo assays were performed to determine the effect of dehydroabietic acid on the cytotoxicity of vincristine.Results:Vincristine and doxorubicin markedly suppressed proliferation and induced apoptosis of REH and CCRF-CEM cells.Survivin expression was upregulated in REH-R cells compared with REH cells.Knockdown of survivin expression obviously restored the sensitivity of REH-R cells to vincristine.Akt phosphorylation was also increased in REH-R cells compared to REH cells.In addition,LY294002,a PI3k/Akt pathway blocker,inhibited survivin expression and enhanced cytotoxicity of vincristine to REH-R cells.Dehydroabietic acid effectively reduced survivin expression in REH-R cells,thereby enhancing the therapeutic effect of vincristine on drug-resistant cells.Survivin overexpression markedly reduced the effect of dehydroabietic acid on enhancing the anti-proliferation and inducing apoptosis effect of vincristine.Moreover,the combination of dehydroabietic acid with vincristine significantly extended the survival rate in a mouse xenograft model of acute lymphoblastic leukemia,compared with vincristine treatment alone.Conclusions:Dehydroabietic acid may be used as a potential candidate for the treatment of acute lymphoblastic leukemia in combination with vincristine.展开更多
本研究采用回顾性方法分析大剂量甲氨喋呤(HD-MTX)为主的HD-MTX-CF+VDT方案在儿童急性淋巴细胞性白血病(ALL)髓外防治中的作用及意义,并分析HD-MTX的毒副作用及动态MTX血药浓度监测在该方案中的重要作用,以避免或减轻HD-MTX的毒副作用,...本研究采用回顾性方法分析大剂量甲氨喋呤(HD-MTX)为主的HD-MTX-CF+VDT方案在儿童急性淋巴细胞性白血病(ALL)髓外防治中的作用及意义,并分析HD-MTX的毒副作用及动态MTX血药浓度监测在该方案中的重要作用,以避免或减轻HD-MTX的毒副作用,及时调整亚叶酸钙(CF)的解救剂量或必要时与以血浆置换,保证化疗的安全性及降低患儿骨髓外复发的几率。对180例ALL患儿先后进行380次HD-MTX-CF+VDT方案的髓外防治,其中诱导缓解期患儿122例,维持期患儿58例;低危组68例、中危组80例、高危组32例。结果表明:HD-MTX的毒副作用包括皮肤黏膜损害、胃肠道反应、肝功能及肾功能受累、发热、骨髓抑制、感染、过敏反应、极少数心肌损害等,占36.3%,均为可逆性损害。本组患儿出现MTX排泄延迟者110例,24小时MTX浓度>10μm o l/L者3例、44小时>1.0μm o l/L者50例、68小时>0.1μm o l/L者57例,以合理调整CF解救剂量及对症治疗保护脏器功能均使MTX血药浓度降到0.1μm o l/L以下的无毒浓度,1例发生肾功能不全并治愈。结论:以HD-MTX为主的髓外防治方案对提高ALL患儿长期缓解及无事件生存率至关重要,但其相关副作用及风险性也随着MTX的剂量增大而增加,且MTX在体内代谢程度存在较大个体差异,因而在治疗过程中动态监测MTX的血药浓度,指导适时适量的CF解救是HD-MTX方案能够安全有效实施的前提和保障。展开更多
文摘Background: The treatment used to combat acute lymphoblastic leukemia (ALL) is multidrug;therefore it is important to use active pharmacovigilance to detect, assess and analyze the likely adverse reactions which may occur during the same period. Objective: To determine the frequency of adverse reactions to chemotherapeutic drugs in children with ALL. Material and Methods: Intensive pharmacovigilance was used to record the reports of adverse reactions to vincristine, L-asparaginase and the vincristine-L-asparaginase combination in children with ALL in a paediatric hospital. For each notification, the adverse reactions were analyzed in order to verify causality. Results: Forty patients were evaluated. Twenty children were female (50.0%) and 20 were male (50%). The children had a mean age, weight and height (±standard deviation: SD) of 8.1 (±3.4) years, 31.4 (±13.9) kg and 1.3 (±0.2) m, respectively. Vincristine was administered to 19 patients, vincristine plus L-asparaginase were given to 19 patients and only 2 patients used L-asparaginase. One-hundred-ninety adverse reactions were detected in the patients, with an average (±SD) of 4.8 (±2.6). Ondansetron was the drug administered for the treating of nausea and vomiting. One hundred eighty-one (95.3%) adverse reactions were identified as “definite”, 5 (2.6%) as “probable” and 4 (2.1%) as “doubtful”. Conclusions: There is a high incidence of adverse reactions by the administration of vincristine and L-asparaginase;the reactions of highest incidence were: nausea, vomiting, neutropenia, diarrhea, constipation, mucositis, headache, and abdominal pain. It is important to promote the detection, collection, reporting, assessment and treatment of ARD’s in children. It is necessary to promote the conduct further studies on pharmacovigilance with this type of treatments and to increase the duration of the studies.
基金supported by Suzhou Science and Technology Development Plan (SKJYD2021047)the Fundation of Suzhou Kowloon Hospital (SZJL202111 and SZJL202104)
文摘Objective:To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia cells.Methods:Acute lymphoblastic leukemia cells REH and CCRFCEM were employed to detect the anti-tumor effect of vincristine and doxorubicin on proliferation and apoptosis using EdU assay,human active caspase-3 Quantikine ELISA kit,and flow cytometry.Vincristine-resistant REH cells(REH-R),survivin knockdown and overexpressing REH cells were established to verify the role of survivin in drug resistance.Additionally,in vitro and in vivo assays were performed to determine the effect of dehydroabietic acid on the cytotoxicity of vincristine.Results:Vincristine and doxorubicin markedly suppressed proliferation and induced apoptosis of REH and CCRF-CEM cells.Survivin expression was upregulated in REH-R cells compared with REH cells.Knockdown of survivin expression obviously restored the sensitivity of REH-R cells to vincristine.Akt phosphorylation was also increased in REH-R cells compared to REH cells.In addition,LY294002,a PI3k/Akt pathway blocker,inhibited survivin expression and enhanced cytotoxicity of vincristine to REH-R cells.Dehydroabietic acid effectively reduced survivin expression in REH-R cells,thereby enhancing the therapeutic effect of vincristine on drug-resistant cells.Survivin overexpression markedly reduced the effect of dehydroabietic acid on enhancing the anti-proliferation and inducing apoptosis effect of vincristine.Moreover,the combination of dehydroabietic acid with vincristine significantly extended the survival rate in a mouse xenograft model of acute lymphoblastic leukemia,compared with vincristine treatment alone.Conclusions:Dehydroabietic acid may be used as a potential candidate for the treatment of acute lymphoblastic leukemia in combination with vincristine.
文摘本研究采用回顾性方法分析大剂量甲氨喋呤(HD-MTX)为主的HD-MTX-CF+VDT方案在儿童急性淋巴细胞性白血病(ALL)髓外防治中的作用及意义,并分析HD-MTX的毒副作用及动态MTX血药浓度监测在该方案中的重要作用,以避免或减轻HD-MTX的毒副作用,及时调整亚叶酸钙(CF)的解救剂量或必要时与以血浆置换,保证化疗的安全性及降低患儿骨髓外复发的几率。对180例ALL患儿先后进行380次HD-MTX-CF+VDT方案的髓外防治,其中诱导缓解期患儿122例,维持期患儿58例;低危组68例、中危组80例、高危组32例。结果表明:HD-MTX的毒副作用包括皮肤黏膜损害、胃肠道反应、肝功能及肾功能受累、发热、骨髓抑制、感染、过敏反应、极少数心肌损害等,占36.3%,均为可逆性损害。本组患儿出现MTX排泄延迟者110例,24小时MTX浓度>10μm o l/L者3例、44小时>1.0μm o l/L者50例、68小时>0.1μm o l/L者57例,以合理调整CF解救剂量及对症治疗保护脏器功能均使MTX血药浓度降到0.1μm o l/L以下的无毒浓度,1例发生肾功能不全并治愈。结论:以HD-MTX为主的髓外防治方案对提高ALL患儿长期缓解及无事件生存率至关重要,但其相关副作用及风险性也随着MTX的剂量增大而增加,且MTX在体内代谢程度存在较大个体差异,因而在治疗过程中动态监测MTX的血药浓度,指导适时适量的CF解救是HD-MTX方案能够安全有效实施的前提和保障。
