Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Pediatrics, Weill Cornell Medical College, New York, NY; and.
Blood Adv. 2021 Jan 26;5(2):496-503. doi: 10.1182/bloodadvances.2020002735.
Adoptive cell therapy using cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CMV-CTLs) has demonstrated efficacy posttransplant. Despite the predicted limited engraftment of CMV-CTLs derived from third-party donors, partially matched third-party donor-derived CMV-CTLs have demonstrated similar response rates to those derived from primary hematopoietic cell transplantation donors. Little is known about the mechanisms through which adoptive cellular therapies mediate durable responses. We performed a retrospective analysis of patients receiving CMV-CTLs for treatment of CMV viremia and/or disease after allogeneic transplant between September of 2009 and January of 2018. We evaluated whether response to adoptively transferred CMV-CTLs correlated with immune reconstitution (IR), using validated CD4+ IR milestones of 50 × 106/L and 200 × 106/L. In this analysis, a cohort of 104 patients received CMV-CTLs derived from a primary transplant donor (n = 25), a third-party donor (n = 76), or both (n = 3). Response to therapy did not increase the likelihood of achieving CD4+ IR milestones at 1 (P = .53 and P > .99) or 2 months (P = .12 and P = .33). The origin of CMV-CTLs did not impact subsequent CD4+ IR. CMV-CTLs appeared to interact with host immunity in mediating responses. Recipients with a baseline CD4 >50 × 106/L had higher response to therapy (P = .02), improved overall survival (P < .001), and protection from CMV-related death (P = .002). Baseline endogenous immunity appears to improve CMV-related and overall survival in this cohort and can be an important marker at the initiation of therapy.
采用细胞毒性 T 淋巴细胞（CTL）治疗巨细胞病毒（CMV）在移植后已显示出疗效。尽管从第三方供体获得的 CMV-CTL 的预期植入有限，但部分匹配的第三方供体衍生的 CMV-CTL 与从原发性造血细胞移植供体获得的 CMV-CTL 具有相似的反应率。关于过继细胞疗法介导持久反应的机制知之甚少。我们对 2009 年 9 月至 2018 年 1 月期间接受 CMV-CTL 治疗 CMV 病毒血症和/或疾病的患者进行了回顾性分析。我们评估了对过继转移的 CMV-CTL 的反应是否与免疫重建（IR）相关，使用了 50×106/L 和 200×106/L 的经验证的 CD4+IR 里程碑。在这项分析中，一组 104 名患者接受了来自原发性移植供体（n=25）、第三方供体（n=76）或两者（n=3）的 CMV-CTL。治疗反应并未增加在 1 个月（P=0.53 和 P＞0.99）或 2 个月（P=0.12 和 P=0.33）时达到 CD4+IR 里程碑的可能性。CMV-CTL 的来源并不影响随后的 CD4+IR。CMV-CTL 似乎通过与宿主免疫相互作用来介导反应。基线 CD4＞50×106/L 的患者对治疗的反应更高（P=0.02），总体生存率提高（P＜0.001），并且对 CMV 相关死亡的保护（P=0.002）。在本队列中，基线内源性免疫似乎改善了 CMV 相关和总体生存率，并且可以作为治疗开始时的重要标志物。
