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实体器官移植后免疫抑制剂引发的新发恶性肿瘤

Immunosuppressant-driven de novo malignant neoplasms after solid-organ transplant.

作者信息

Billups Kelsey, Neal Jennifer, Salyer Jeanne

机构信息

Virginia Commonwealth University, Richmond, Virginia.

出版信息

Prog Transplant. 2015 Jun;25(2):182-8. doi: 10.7182/pit2015826.

DOI:10.7182/pit2015826
PMID:26107280
Abstract

Solid-organ transplant recipients are at a 3- to 5-fold increased risk of a de novo malignant neoplasm developing compared with the general population. The most frequently developed virus-associated malignant neoplasms are Kaposi sarcoma (standardized incidence ratio [SIR], 208.0), nonmelanoma skin cancer (SIR, 28.6), and posttransplant lymphoproliferative disorder, primarily non-Hodgkin lymphoma (SIR, 8.1). Immunosuppressive agents such as corticosteroids, antimetabolites, calcineurin inhibitors, and mammalian target of rapamycin (mTOR) inhibitors play a key role in either causing or preventing this complication. It is hypothesized that some of these regimens can impair cancer surveillance, facilitate the action of oncogenic viruses, and promote direct oncogenic activity. Evolving research has shown promising dual antitumor and immunosuppressive properties of the mTOR inhibitor class. The effective management of posttransplant neoplasms most likely involves the use of these medications among other preventative options. These measures include monitoring certain viral loads as well as immunosuppressant drug levels. Reducing these levels to as low as possible for healthy engraftment and altering regimens when appropriate are management strategies that could lessen this complication of solid-organ transplant. More studies examining the effects of therapeutic drug monitoring are needed to determine specific plasma drug concentrations that will ensure organ engraftment without the development of de novo malignant neoplasms.

摘要

与普通人群相比,实体器官移植受者发生新发恶性肿瘤的风险增加3至5倍。最常发生的病毒相关恶性肿瘤是卡波西肉瘤(标准化发病率[SIR],208.0)、非黑色素瘤皮肤癌(SIR,28.6)以及移植后淋巴细胞增生性疾病,主要是非霍奇金淋巴瘤(SIR,8.1)。皮质类固醇、抗代谢物、钙调神经磷酸酶抑制剂和雷帕霉素靶蛋白(mTOR)抑制剂等免疫抑制剂在引发或预防这种并发症中起关键作用。据推测,其中一些治疗方案会损害癌症监测、促进致癌病毒的作用并促进直接致癌活性。不断发展的研究表明,mTOR抑制剂类具有令人期待的双重抗肿瘤和免疫抑制特性。移植后肿瘤的有效管理很可能涉及在其他预防措施中使用这些药物。这些措施包括监测某些病毒载量以及免疫抑制剂药物水平。将这些水平降至尽可能低以实现健康植入,并在适当的时候改变治疗方案,这些管理策略可能会减少实体器官移植的这种并发症。需要更多研究来考察治疗药物监测的效果,以确定能确保器官植入且不发生新发恶性肿瘤的具体血浆药物浓度。

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