Goldsmith Scott R, Ghobadi Armin, DiPersio John F
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
Front Oncol. 2020 Dec 22;10:608916. doi: 10.3389/fonc.2020.608916. eCollection 2020.
Allogeneic hematopoietic cell transplantation (allo-HCT) and chimeric antigen receptor T cell (CAR T) therapy are the main modalities of adoptive cellular immunotherapy that have widely permeated the clinical space. The advent of both technologies revolutionized treatment of many hematologic malignancies, both offering the chance at sustained remissions for patients who would otherwise invariably succumb to their diseases. The understanding and exploitation of the nonspecific alloreactivity of allo-HCT and the graft-versus-tumor effect is contrasted by the genetically engineered precision of CAR T therapy. Historically, those with relapsed and refractory hematologic malignancies have often been considered for allo-HCT, although outcomes vary dramatically and are associated with potential acute and chronic toxicities. Such patients, mainly with B-lymphoid malignancies, may now be offered CAR T therapy. Yet, a lack of prospective data to guide decisions thereafter requires individualized approaches on whether to proceed to allo-HCT or observe. The continued innovations to make CAR T therapy more effective and accessible will continue to alter such approaches, but similar innovations in allo-HCT will likely result in similarly improved clinical outcomes. In this review, we describe the history of the two platforms, dissect the clinical indications emphasizing their intertwining and competitive roles described in trials and practice guidelines, and highlight innovations in which they complement or inform one another.
异基因造血细胞移植(allo-HCT)和嵌合抗原受体T细胞(CAR T)疗法是过继性细胞免疫疗法的主要形式,已广泛应用于临床。这两种技术的出现彻底改变了许多血液系统恶性肿瘤的治疗方式,都为那些否则将不可避免死于疾病的患者提供了持续缓解的机会。allo-HCT的非特异性同种异体反应性和移植物抗肿瘤效应的理解与利用,与CAR T疗法的基因工程精准性形成对比。从历史上看,复发和难治性血液系统恶性肿瘤患者常被考虑进行allo-HCT,尽管结果差异很大且与潜在的急性和慢性毒性相关。这类主要患有B淋巴细胞恶性肿瘤的患者现在可能会接受CAR T疗法。然而,缺乏前瞻性数据来指导后续决策,这就需要针对是否进行allo-HCT或观察采取个体化方法。使CAR T疗法更有效且更易获得的持续创新将继续改变此类方法,但allo-HCT的类似创新可能会带来同样改善的临床结果。在本综述中,我们描述了这两种平台的历史,剖析临床适应证,强调它们在试验和实践指南中所描述的相互交织和竞争的作用,并突出它们相互补充或相互启发的创新之处。
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