Dainiak Nicholas, Waselenko Jamie K, Armitage James O, MacVittie Thomas J, Farese Ann M
The Bridgeport Hospital, Bridgeport, CT 06610, USA.
Hematology Am Soc Hematol Educ Program. 2003:473-96. doi: 10.1182/asheducation-2003.1.473.
Since the terrorist attack of September 11, 2001, preparation by the health care system for an act of terrorism has been mandated by leaders of governments. Scenarios for terrorist acts involving radioactive material have been identified, and approaches to management (based on past experience from atomic weapons detonations and radiation accidents) have been developed. Because of their experience in managing patients with profound cytopenia and/or marrow aplasia, hematologists will be asked to play a significant role in evaluating and treating victims of mass accidental or deliberate exposure to radiation. This review provides a framework for understanding how radiation levels are quantified, how radiation alters the function of hematopoietic (and nonhematopoietic) cells and tissues, and how victims receiving a significant radiation dose can be identified and managed. In Section I, Dr. Nicholas Dainiak reviews four components of the Acute Radiation Syndrome: the hematopoietic, neurovascular, gastrointestinal and cutaneous subsyndromes. Clinical signs and symptoms are discussed for exposed individuals at the time of initial presentation (the prodromal phase) and during their course of disease (the manifest illness). In Section II, he presents clinical and laboratory methods to assess radiation doses, including time to onset and severity of vomiting, rate of decline in absolute blood lymphocyte count and the appearance of chromosome aberrations such as dicentrics and ring forms. Potential scenarios of a radiation terrorist event are reviewed, and methods for initial clinical assessment, triage, and early management of the acute radiation syndrome and its component subsyndromes are summarized. In Section III, Dr. Jamie Waselenko reviews the hematopoietic syndrome, and presents guidelines for the use of cytokine therapy, antibiotics, and supportive care that have been developed by the Strategic National Pharmaceutical Stockpile Working Group. Results of preclinical and clinical growth factor therapy studies with G-CSF, GM-CSF, pegylated G-CSF, SCF, and IL-3 are summarized. When and how potassium iodide should be used after exposure to radioiodines is also reviewed. In Section IV, Dr. James Armitage describes a narrow "window" of 7 to 10 Gy where therapy with stem cell transplantation may be appropriate. Victims who are candidates for allotransplantation should not have major trauma or significant injury to other (nonhematopoietic) tissues. Rarely, victims may have an identical sibling or autologous stored marrow or blood stem cells, in which case the threshold for transplantation is 4 Gy. In Section V, Dr. Thomas MacVittie describes new directions for therapy, using cytokines such as IL-7, keratinocyte growth factor, and FLT-3. The potential for combinations of cytokines to enhance hematopoietic recovery is also reviewed.
自2001年9月11日恐怖袭击事件以来,政府领导人已要求医疗保健系统为应对恐怖主义行为做好准备。已确定了涉及放射性物质的恐怖主义行为场景,并制定了管理方法(基于过去原子弹爆炸和辐射事故的经验)。由于血液学家在管理严重血细胞减少和/或骨髓再生障碍患者方面的经验,他们将被要求在评估和治疗大规模意外或故意辐射暴露受害者方面发挥重要作用。本综述提供了一个框架,以了解如何量化辐射水平、辐射如何改变造血(和非造血)细胞及组织的功能,以及如何识别和管理接受大量辐射剂量的受害者。在第一部分,尼古拉斯·戴尼亚克博士回顾了急性放射综合征的四个组成部分:造血、神经血管、胃肠道和皮肤亚综合征。讨论了暴露个体在初次就诊时(前驱期)和疾病过程中(明显疾病期)的临床体征和症状。在第二部分,他介绍了评估辐射剂量的临床和实验室方法,包括呕吐开始时间和严重程度、绝对血淋巴细胞计数下降速率以及染色体畸变(如双着丝粒和环状形式)的出现。回顾了辐射恐怖事件的潜在场景,并总结了急性放射综合征及其组成亚综合征的初始临床评估、分诊和早期管理方法。在第三部分,杰米·瓦塞连科博士回顾了造血综合征,并介绍了战略国家药品储备工作组制定的细胞因子治疗、抗生素和支持性护理的使用指南。总结了G-CSF、GM-CSF、聚乙二醇化G-CSF、SCF和IL-3的临床前和临床生长因子治疗研究结果。还回顾了接触放射性碘后何时以及如何使用碘化钾。在第四部分,詹姆斯·阿米蒂奇博士描述了一个7至10戈瑞的狭窄“窗口期”,在此期间干细胞移植治疗可能是合适的。适合进行同种异体移植的受害者不应有重大创伤或其他(非造血)组织的严重损伤。很少有受害者可能有相同的同胞或自体储存的骨髓或血液干细胞,在这种情况下,移植阈值为4戈瑞。在第五部分,托马斯·麦克维蒂博士描述了使用IL-7、角质形成细胞生长因子和FLT-3等细胞因子的治疗新方向。还回顾了细胞因子组合增强造血恢复的潜力。