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8 例放射事故后辐射诱导骨髓抑制患者采用细胞因子联合治疗促进造血恢复

Hematopoietic Recovery using Multi-Cytokine Therapy in 8 Patients Presenting Radiation-Induced Myelosuppression after Radiological Accidents.

机构信息

Institute of Radioprotection and Nuclear Safety (IRSN), Health Division, BP17, 92262 Fontenay-aux-Roses, France.

Military Hospital, Department of Hematology and Chemotherapy for Solid Tumors, Sofia, Bulgaria.

出版信息

Radiat Res. 2021 Dec 1;196(6):668-679. doi: 10.1667/RADE-21-00169.1.

DOI:10.1667/RADE-21-00169.1
PMID:34554263
Abstract

Treatment of accidental radiation-induced myelosuppression is primarily based on supportive care and requires specific treatment based on hematopoietic growth factors injection or hematopoietic cell transplantation for the most severe cases. The cytokines used consisted of pegylated erythropoietin (darbepoetin alfa) 500 IU once per week, pegylated G-CSF (pegfilgrastim) 6 mg × 2 once, stem cell factor 20 µg.kg-1 for five days, and romiplostim (TPO analog) 10 µg.kg -1 once per week, with different combinations depending on the accidents. As the stem cell factor did not have regulatory approval for clinical use in France, the French regulatory authorities (ANSM, formerly, AFSSAPS) approved their compassionate use as an investigational drug "on a case-by-case basis". According to the evolution and clinical characteristics, each patient's treatment was adopted on an individual basis. Daily blood count allows initiating G-CSF and SCF delivery when granulocyte <1,000/mm3, TPO delivery when platelets <50,000/mm3, and EPO when Hb<80 g/L. The length of each treatment was based on blood cell recovery criteria. The concept of "stimulation strategy" is linked to each patient's residual hematopoiesis, which varies among them, depending on the radiation exposure's characteristics and heterogeneity. This paper reports the medical management of 8 overexposed patients to ionizing radiation. The recovery of bone marrow function after myelosuppression was accelerated using growth factors, optimized by multiple-line combinations. Particularly in the event of prolonged exposure to ionizing radiation in dose ranges inducing severe myelosuppression (in the order of 5 to 8 Gy), with no indication of hematopoietic stem cell transplantation.

摘要

意外辐射诱导的骨髓抑制的治疗主要基于支持性护理,并根据造血生长因子注射或造血细胞移植的需要,对最严重的病例进行特定治疗。使用的细胞因子包括每周一次的聚乙二醇化促红细胞生成素(达贝泊汀α)500IU、一次的聚乙二醇化 G-CSF(培非格司亭)6mg×2、连续五天的干细胞因子 20μg/kg-1 和每周一次的罗米司亭(TPO 类似物)10μg/kg-1,具体组合取决于事故情况。由于干细胞因子在法国没有获得临床使用的监管批准,法国监管当局(ANSM,前身为 AFSSAPS)批准了其作为研究药物的同情使用,“逐案批准”。根据病情的发展和临床特点,每位患者的治疗都是个体化的。每天进行血液计数,当粒细胞<1000/mm3 时开始给予 G-CSF 和 SCF 治疗,当血小板<50000/mm3 时给予 TPO 治疗,当 Hb<80g/L 时给予 EPO 治疗。每次治疗的持续时间基于血细胞恢复标准。“刺激策略”的概念与每位患者的剩余造血功能有关,每位患者的剩余造血功能因辐射暴露的特点和异质性而异。本文报告了 8 名过量辐射暴露的患者的医疗管理情况。通过多种组合的优化,使用生长因子加速了骨髓抑制后的骨髓功能恢复。特别是在长时间暴露于剂量范围诱导严重骨髓抑制(5 至 8Gy 左右)的电离辐射时,没有造血干细胞移植的指征。

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Hematopoietic Recovery using Multi-Cytokine Therapy in 8 Patients Presenting Radiation-Induced Myelosuppression after Radiological Accidents.8 例放射事故后辐射诱导骨髓抑制患者采用细胞因子联合治疗促进造血恢复
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IL-12 facilitates both the recovery of endogenous hematopoiesis and the engraftment of stem cells after ionizing radiation.白细胞介素-12有助于内源性造血功能的恢复以及电离辐射后干细胞的植入。
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Monitoring of residual hematopoiesis after total body irradiation in humans as a model for accidental x-ray exposure: dose-effect and failure of ex vivo expansion of residual stem cells in view of autografting.以人体全身照射后残余造血功能监测作为意外X射线照射模型:剂量效应及考虑自体移植时残余干细胞体外扩增失败。
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