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首页> 美国卫生研究院文献>Springer Open Choice >Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse
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Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse

机译：大剂量依托泊苷药代动力学在异基因造血干细胞移植治疗儿童急性淋巴细胞白血病之前的临床和体外研究对移植后白血病复发风险的影响

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The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC–UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1–1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1–0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1–0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material.
机译：研究了异体造血干细胞移植（allo-HSCT）当天依托泊苷（VP-16）的血浆浓度对急性淋巴细胞白血病（ALL）儿童无白血病生存的影响。另外，评估了VP-16对淋巴细胞增殖，细胞毒性活性以及对Th1 / Th2细胞因子应答的体外作用。在31名接受allo-HSCT的儿童中，使用HPLC-UV方法在输注后直至120小时确定了VP-16血浆浓度。对于提及的体外研究，使用在all-HSCT日观察到的VP-16血浆浓度。在84％的儿童中，在输注结束后72小时（即应进行all-HSCT时）VP-16血浆浓度（0.1–1.5μg/ mL）可定量。药物输注结束后4天，在20名（65％）儿童中进行了all-HSCT，在其中12名（39％）的血浆中仍可检测到VP-16（0.1-0.9μg/ mL）。移植后ALL复发发生在四名儿童中，他们全部在allo-HSCT当天血浆中检出VP-16（0.1–0.8μg / mL），而未检出VP-16的儿童未见复发。在体外研究中，VP-16证明了其浓度和暴露时间对刺激淋巴细胞的增殖活性有影响。异体-HSCT日血浆中VP-16的存在可能表明对移植物抗白血病（GvL）反应有不利影响，并增加了移植后ALL复发的风险。因此，如果在VP-16给药后72小时其血浆浓度仍高于0.1μg/ mL，则应考虑将移植后推迟24小时以保护GvL效应细胞免受移植物的侵害。

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