Abstract
Allogeneic hematopoietic cell transplantation and cell therapy (TCT) are potentially lifesaving treatments for patients with high-risk hematologic malignancies and life-threatening acquired and genetic hematologic disorders. However, these treatments face significant challenges, particularly in the risks of relapse and severe toxicity, leading to both relapse-related and non-relapse mortality (NRM). The immune system plays a critical role in controlling these risks, but predictive immune biomarkers for relapse and toxicity have yet to be fully established. To better understand factors driving outcomes in TCT recipients, researchers are increasingly relying on minimally invasive specimens for analysis, such as peripheral blood. These liquid biopsies provide a cost-effective and rapid means to evaluate parameters such as minimal residual disease and genomic mutation profiles. The evolution of these techniques opens new possibilities for monitoring immune reconstitution, including tracking immune cell development and the diversity of surface and secreted biomarkers. This review presents a practical guideline for establishing an immune monitoring program tailored to the TCT environment. By adopting a proactive, harmonized approach, such programs can enhance prognosis prediction and enable early relapse detection, potentially surpassing traditional diagnostic methods. While recent advancements are promising, considerable progress is still needed to make liquid biopsies a routine component of clinical practice. © 2025 International Society for Cell & Gene Therapy. Published by Elsevier Inc.