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Evaluation of the effectiveness of packed red blood cell irradiation by a linear accelerator

机译:线性加速器对充填红细胞照射的有效性评估

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Irradiation of blood components with ionizing radiation generated by a specific device is recommended to prevent transfusion-associated graft-versus-host disease. However, a linear accelerator can also be used in the absence of such a device, which is the case of the blood bank facility studied herein. In order to evaluate the quality of the irradiated packed red blood cells, this study aimed to determine whether the procedure currently employed in the facility is effective in inhibiting the proliferation of T lymphocytes without damaging blood components.The proliferation of T lymphocytes, plasma potassium levels, and the degree of hemolysis were evaluated and compared to blood bags that received no irradiation. Packed red blood cell bags were irradiated at a dose of 25?Gy in a linear accelerator. For this purpose, a container was designed to hold the bags and to ensure even distribution of irradiation as evaluated by computed tomography and dose-volume histogram.Irradiation was observed to inhibit the proliferation of lymphocytes. The percentage of hemolysis in irradiated bags was slightly higher than in non-irradiated bags (p-value >0.05), but it was always less than 0.4% of the red cell mass. Although potassium increased in both groups, it was more pronounced in irradiated red blood cells, especially after seven days of storage, with a linear increase over storage time.The findings showed that, at an appropriate dosage and under validated conditions, the irradiation of packed red blood cells in a linear accelerator is effective, inhibiting lymphocyte proliferation but without compromising the viability of the red cells. class="kwd-title">Keywords: Blood safety, Hemotherapy service, T-lymphocytesIntroductionTransfusion-associated graft-versus-host disease (TA-GvHD) is a rare and acute delayed transfusion reaction which occurs after the transfusion of blood components; this complication is correlated to a high mortality rate. The main mechanism for the occurrence of TA-GVHD is the transfer of T lymphocytes from the blood donor that damage and promote a response in the tissues of the recipient. After recognizing host tissues as foreign, the cytokines released by transfused T lymphocytes, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), drive an inflammatory response. These cytokines activate inflammatory cells, including natural killer (NK) cells, macrophages, and other T lymphocytes, resulting in the destruction of host tissues thereby causing TA-GVHD.1,2 Another mechanism for the occurrence of TA-GVHD occurs through donor-recipient HLA incompatibility.3 The development of this transfusion reaction appears to relate to the number and viability of T lymphocytes transfused in blood components (although this number is not yet known), to the level of immunosuppression of the patient, and to the extent that antigens of the HLA system are common to both the donor and recipient.4,5 Therefore, the greater the number of blood components received, the greater the chance of TA-GVHD occurring in at-risk patients.In susceptible patients, TA-GVHD occurs when the number of viable transfused lymphocytes is more than 1?×?104?cells/kg of body weight.3,5 It is known that non-leukodepleted packed red blood cell (PRBC) bags have approximately 2–3?×?109 leukocytes, whereas leukodepleted PRBC bags have from 2–3?×?106 leukocytes. Therefore, even leukodepletion is not able to protect these patients from TA-GVHD.3,6 In situations in which the patient has a healthy immune system, lymphocytes are destroyed. However, in immunosuppressed patients, these cells are not destroyed by the recipient's immune system and so after proliferation and producing cytokines, the lymphocytes may cause a TA-GvHD-related inflammatory response. Thus, the only effective method to prevent this disease completely is to inactivate donor lymphocytes by irradiating blood components.Determination No. 34 of the Ministry of Health of Brazil/National Health Surveillance Agency (ANVISA) states that the irradiation of blood and blood components should be performed in a specific cell irradiator, and that when this equipment is not available, irradiation can be carried out in a linear accelerator used for radiation therapy.7 Using linear accelerators instead of cell irradiators has been the subject of discussion among authors. Although Vetter and Dodd consider the performance of both methods to be similar,8 dose uniformity may fail to meet the quality standards in linear accelerators if the method is not standardized. This was also reported by Janatpour et al. on comparing the irradiation of blood components with X-rays and gamma-rays.9 Bashir et al. demonstrated similar effects in the dosage of potassium and in the degree of hemolysis in red blood cells subjected to X-rays and gamma radiation, and suggested employing linear accelerators in the place of radioactive equipment due to the lower maintenance c
机译:建议使用特定设备产生的电离辐射照射血液成分,以防止输血相关的移植物抗宿主病。但是,在没有这种装置的情况下也可以使用线性加速器,这是本文研究的血库设备的情况。为了评估被辐照的堆积红细胞的质量,本研究旨在确定该设施中目前采用的程序是否有效抑制T淋巴细胞的增殖而不损害血液成分.T淋巴细胞的增殖,血浆钾水平评估溶血程度,并与未接受辐射的血袋进行比较。在线性加速器中以25?Gy的剂量辐照装好的红细胞袋。为此目的,设计了一个容器来容纳袋子并通过计算机断层扫描和剂量体积直方图评估辐射的均匀分布,并观察到辐射抑制了淋巴细胞的增殖。辐照袋中的溶血百分比比未辐照袋中的溶血百分比略高( p 值> 0.05),但始终小于红细胞质量的0.4%。尽管两组中的钾均增加,但在受辐照的红细胞中尤为明显,尤其是在储存7天后,随着储存时间的增加呈线性增加。研究结果表明,在适当的剂量和有效条件下,包装后的辐照线性加速器中的红细胞有效,可抑制淋巴细胞增殖,但又不损害红细胞的生存能力。 class =“ kwd-title”>关键字:血液安全性,血液治疗服务,T淋巴细胞简介与输血相关的移植物抗-宿主疾病(TA-GvHD)是一种罕见的急性延迟性输血反应,发生在输血后;这种并发症与高死亡率有关。发生TA-GVHD的主要机制是从供血者体内转移T淋巴细胞,从而破坏并促进受体组织的反应。在将宿主组织识别为异物后,由输血T淋巴细胞释放的细胞因子(如白介素1(IL-1)和肿瘤坏死因子(TNF))驱动炎症反应。这些细胞因子激活炎性细胞,包括自然杀伤(NK)细胞,巨噬细胞和其他T淋巴细胞,导致宿主组织破坏,从而引起TA-GVHD。1,2,TA-GVHD发生的另一种机制是通过供体- 3这种输血反应的进展似乎与血液成分中输注的T淋巴细胞的数量和生存能力有关(尽管尚不清楚该数字),与患者的免疫抑制水平有关,并且在一定程度上HLA系统的抗原对于供体和受体都是共同的。4,5因此,高危患者接受的血液成分越多,发生TA-GVHD的机会就越大。当存活的输血淋巴细胞数量超过1?×?10 4 ?细胞/ kg体重时,就会发生这种情况。3,5众所周知,非白血球充填型红细胞(PRBC)袋大约有2–3?×?10 9 白细胞,而去白细胞的PRBC袋中有2–3?×?10 6 白细胞。因此,即使白细胞去除也不能保护这些患者免受TA-GVHD的侵害。3,6。在患者具有健康免疫系统的情况下,淋巴细胞会被破坏。但是,在免疫抑制的患者中,这些细胞不会被受体的免疫系统破坏,因此在增殖并产生细胞因子后,淋巴细胞可能会引起TA-GvHD相关的炎症反应。因此,完全预防这种疾病的唯一有效方法是通过辐照血液成分来使供体淋巴细胞失活。巴西卫生部/国家卫生监督局(ANVISA)第34号裁决指出,应辐照血液和血液成分可以在特定的细胞辐照器中进行辐照,并且当该设备不可用时,可以在用于放射疗法的线性加速器中进行辐照。7使用线性加速器代替细胞辐照器一直是作者讨论的主题。尽管Vetter和Dodd认为两种方法的性能相似,但如果该方法未标准化,则剂量均匀性可能无法满足线性加速器的质量标准。 Janatpour等人也报道了这一点。 Bashir等[9]研究了用X射线和γ射线比较血液成分的辐射。在X射线和γ射线照射的红细胞中,对钾的剂量和溶血度具有相似的效果,并且由于维护成本较低,因此建议使用线性加速器代替放射性设备

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