CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Measurable residual disease in acute lymphoblastic leukemia: How low is low enough?
Measurable residual disease in acute lymphoblastic leukemia: How low is low enough?
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急性淋巴细胞白血病(ALL)可测量残留病灶(MRD)定量是一种成熟的临床工具,可在化疗、免疫治疗和/或移植治疗过程中对患者进行风险分层。随着技术进步,新一代测序(NGS)或新一代流式细胞术(NGF)检测极低肿瘤负荷的灵敏度不断提高。如今,过去使用灵敏度较低方法判定为MRD阴性的患者,也可能检出并精确定量MRD。ALL病灶负荷持续存在或复发且高于10⁻⁴(0.01%),通常被视为临床决策的最低阈值;但借助NGS和NGF,临床医生现在可能需要面对低至10⁻⁶(0.0001%,即每百万白细胞中一个白血病细胞)的可定量病灶负荷进行决策。新兴数据表明,灵敏度更高的方法更善于识别复发风险最低的患者;但对于病灶负荷可定量且低于10⁻⁴者,是否应给予贝林妥欧单抗或嵌合抗原受体(CAR)T细胞治疗,或转而进行异基因造血细胞移植(alloHCT),仍有争议。随着更多证据支持将高灵敏度MRD定量纳入临床照护,并结合患者个体基因型解读MRD,未来可能更容易识别可避免alloHCT、甚至可降低治疗强度的患者。
Quantification of measurable residual disease (MRD) in acute lymphoblastic leukemia (ALL) is a well-established clinical tool used to risk stratify patients during the course of chemotherapy, immunotherapy, and/or transplant therapy. As technologies evolve, the sensitivity for quantifying exceptionally low disease burden using either next generation sequencing (NGS) or next generation flow cytometry (NGF) has improved. It is now possible to detect MRD and quantify it precisely in patients who would previously have been deemed MRD negative by older, lower sensitivity methods. Persistence or recurrence of ALL disease burden above 10 -4 (0. 01%) is accepted as the minimum threshold for making clinical decisions, but with NGS and NGF, clinicians now confront decision-making with disease burdens sometimes quantified to as low as 10 -6 (0.
0001%, or one leukemia cell in a million leukocytes). Emerging data suggest these higher sensitivity methods are superior for identifying patients at lowest risk for relapse, but it remains controversial whether to institute therapies such as blinatumomab or chimeric antigen receptor (CAR)-T cells or move patients to allogeneic hematopoietic cell transplant (alloHCT) when they have quantifiable disease burden less than 10 -4 .
With additional evidence to facilitate integration of highly sensitive MRD quantification into clinical care and to contextualize MRD within the genotype of individual patients, it will likely be increasingly possible to identify patients able to avoid alloHCT and potentially even de-escalate therapy.
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