Receptors

受体
  • 文章类型: Journal Article
    背景:血小板生成素受体激动剂(TPO-RA)用于治疗原发性免疫性血小板减少症(ITP)。一些患者在维持止血血小板计数的同时停止治疗。
    目标:就ITP中何时考虑逐渐减少TPO-RA达成专家共识,如何减少患者的治疗,停药后如何监测患者,以及如何重新开始治疗。
    方法:我们使用了RAND/UCLA修改的Delphi面板方法。评级由每个专家在会议之前和之后独立完成。第二轮评级用于制定小组的指导。该小组是双盲的:赞助商和非主席专家不知道彼此的身份。
    结果:根据患者血小板计数制定了关于儿童和成人TPO-RA何时适合锥化的指南,出血史,加强治疗,创伤风险,和使用抗凝剂/血小板抑制剂。例如,在血小板计数正常/高于正常的患者中逐渐减少TPO-RA是合适的,没有大出血史,并且在过去6个月中不需要加强治疗;对于血小板计数低的患者,不宜逐渐减少TPO-RA。ITP持续时间,在TPO-RA上的几个月,或血小板对TPO-RA的反应时机对小组关于锥度适当性的指导没有影响。关于如何减少患者的治疗的指导,停药后如何监测患者,以及如何重新开始治疗也提供了。
    结论:本指南可以支持临床决策和临床试验的发展,前瞻性测试逐渐减少TPO-RA的安全性。
    BACKGROUND: Thrombopoietin receptor agonists (TPO-RAs) are used to treat primary immune thrombocytopenia (ITP). Some patients have discontinued treatment while maintaining a hemostatic platelet count.
    OBJECTIVE: To develop expert consensus on when it is appropriate to consider tapering TPO-RAs in ITP, how to taper patients off therapy, how to monitor patients after discontinuation, and how to restart therapy.
    METHODS: We used a RAND/UCLA modified Delphi panel method. Ratings were completed independently by each expert before and after a meeting. Second-round ratings were used to develop the panel\'s guidance. The panel was double-blinded: The sponsor and nonchair experts did not know each other\'s identities.
    RESULTS: Guidance on when it is appropriate to taper TPO-RAs in children and adults was developed based on patient platelet count, history of bleeding, intensification of treatment, trauma risk, and use of anticoagulants/platelet inhibitors. For example, it is appropriate to taper TPO-RAs in patients who have normal/above-normal platelet counts, have no history of major bleeding, and have not required an intensification of treatment in the past 6 months; it is inappropriate to taper TPO-RAs in patients with low platelet counts. Duration of ITP, months on TPO-RA, or timing of platelet response to TPO-RA did not have an impact on the panel\'s guidance on appropriateness to taper. Guidance on how to taper patients off therapy, how to monitor patients after discontinuation, and how to restart therapy is also provided.
    CONCLUSIONS: This guidance could support clinical decision making and the development of clinical trials that prospectively test the safety of tapering TPO-RAs.
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  • 文章类型: Journal Article
    免疫效应细胞(IEC)疗法在大量血液癌症患者中提供持久和持续的缓解。虽然这些独特的免疫疗法在许多疾病状态下改善了儿童和成人患者的预后,作为生活药物,它们的毒性特征,包括细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS),与传统的癌症疗法明显不同。在文章准备的时候,美国食品和药物管理局(FDA)已经批准了tisagenlecleucel,axicabtageneciloleucel,和brexucabtageneautoleucel,所有这些都是基于基因修饰的T细胞的IEC疗法,这些T细胞被设计为表达嵌合抗原受体(CAR),预计其他产品将很快获得上市许可,并在适当时候进入临床开发。作为IEC疗法,尤其是CAR-T细胞疗法,进入更广泛的临床应用,有必要明确,关于毒性管理的有凝聚力的建议,促使癌症免疫治疗协会(SITC)召集专家小组制定临床实践指南。小组讨论了在IEC治疗的背景下对常见毒性的识别和管理,包括用于监测的基线实验室参数,发病的时机,和药物干预,最终形成基于证据和共识的建议,以协助医疗专业人员决策并改善患者预后。
    Immune effector cell (IEC) therapies offer durable and sustained remissions in significant numbers of patients with hematological cancers. While these unique immunotherapies have improved outcomes for pediatric and adult patients in a number of disease states, as \'living drugs,\' their toxicity profiles, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), differ markedly from conventional cancer therapeutics. At the time of article preparation, the US Food and Drug Administration (FDA) has approved tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel, all of which are IEC therapies based on genetically modified T cells engineered to express chimeric antigen receptors (CARs), and additional products are expected to reach marketing authorization soon and to enter clinical development in due course. As IEC therapies, especially CAR T cell therapies, enter more widespread clinical use, there is a need for clear, cohesive recommendations on toxicity management, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of common toxicities in the context of IEC treatment, including baseline laboratory parameters for monitoring, timing to onset, and pharmacological interventions, ultimately forming evidence- and consensus-based recommendations to assist medical professionals in decision-making and to improve outcomes for patients.
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  • 文章类型: Journal Article
    急性白血病是一系列快速发展的疾病,无论年龄或性别,都会影响广泛的患者。急性白血病患者的传统治疗选择包括化疗和造血细胞移植。癌症免疫疗法的出现对急性白血病的治疗产生了重大影响。新型免疫治疗剂,包括抗体-药物缀合物,双特异性T细胞衔接者,和嵌合抗原受体T细胞疗法具有疗效,最近已被美国食品和药物管理局(FDA)批准用于治疗急性白血病患者。癌症免疫治疗协会(SITC)召集了一个专家小组,以制定一项临床实践指南,该指南由关于治疗急性淋巴细胞白血病和急性髓细胞性白血病的免疫治疗的共识建议组成。
    Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment of patients with acute leukemia. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop a clinical practice guideline composed of consensus recommendations on immunotherapy for the treatment of acute lymphoblastic leukemia and acute myeloid leukemia.
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