CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Donor lymphocyte infusion as immune modulation after pediatric allogeneic transplantation.
Donor lymphocyte infusion as immune modulation after pediatric allogeneic transplantation.
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复发仍然是儿童血液系统恶性肿瘤异基因造血细胞移植后治疗失败的主要原因。供者淋巴细胞输注(DLI)提供了一种独特可及且可扩展的非工程化过继性细胞治疗形式。尽管历史上被视为挽救性治疗,但新兴数据支持将DLI从挽救性治疗转向战略性免疫调节的范式转变。本综述综合了DLI在儿童中应用的生物学依据和临床证据,并在必要时整合成人数据以界定可转化的原则。在不同平台上,结局取决于时机、疾病负荷和免疫背景。
我们强调预防性和抢先性DLI优于治疗性使用,并综述了当代结构化方法,这些方法依赖于以低剂量和安全剂量开始治疗,并根据严格的耐受性和监测标准进行剂量递增。特别关注了单倍体相合移植以及限制基于T细胞干预的免疫逃逸机制,如HLA丢失。
此外,我们探讨了新兴联合方案,包括DLI联合blinatumomab用于B细胞急性淋巴细胞白血病,以及联合去甲基化药物用于髓系恶性肿瘤。
最后,我们讨论了T细胞亚群调控以减轻移植物抗宿主病,同时保留移植物抗白血病效应。所有这些数据支持一个现代儿童DLI框架,该框架优先考虑早期、基于生物学的干预和合理联合,并强调迫切需要儿童特异性的前瞻性研究。
Relapse remains a leading cause of failure after allogeneic hematopoietic cell transplantation for pediatric hematologic malignancies. Donor lymphocyte infusion (DLI) offers a uniquely accessible and scalable form of nonengineered adoptive cellular therapy.
Although historically viewed as salvage therapy, emerging data support a paradigm shift toward using DLI as strategic immune modulation rather than rescue. This review synthesizes the biological rationale and clinical evidence for DLI in children, integrating the adult data when necessary to define translatable principles. Across platforms, outcomes rely on timing, disease burden, and the immune context.
We highlight the superiority of prophylactic and preemptive DLI over therapeutic use and review contemporary structured approaches relying on treatment initiation at low and safe doses and escalation based on strict tolerance and monitoring criteria. Special consideration is given to haploidentical transplantation and mechanisms of immune escape such as HLA loss that limit T-cell-based interventions.
Furthermore, we examine emerging combinations, including DLI with blinatumomab in B-cell acute lymphoblastic leukemia and hypomethylating agents in myeloid malignancies.
Finally, we discuss T-cell subset manipulation to mitigate graft-versus-host disease while preserving the graft-versus-leukemia effects. All these data support a modern framework for pediatric DLI that prioritizes early, biology-informed interventions and rational combinations, underscoring the urgent need for pediatric-specific prospective studies.
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