Harmonized Immune Recovery Monitoring after HCT: Evidence & Practical Guidance from the Westhafen Intercontinental Group Open Access

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative option for patients with high-risk malignancies and non-malignant disorders. Long-term survival depends on robust immune reconstitution (IR), which governs overall immune homeostasis and risks of infection, graft-versus-host disease, and relapse. However, despite its centrality to post-transplant outcomes, IR is not consistently monitored across transplant centers, limiting ability to generate meaningful, comparable, and translatable data. This review synthesizes current knowledge on numerical and functional IR milestones following allo-HCT, with a primary focus on flow cytometry-based monitoring of key immune cell subsets. Importantly, early CD4+ T cell recovery (achieving >50 cells/µL by Day 100 post-transplant), is supported by strong clinical evidence and correlates with improved outcomes. While emerging data suggest that additional subsets -CD8+ T cells, NK cells, B cells, naïve and recent thymic emigrant T cells, and γδ T cells - may also influence clinical trajectories, further harmonized, multicenter studies are needed to validate prognostic relevance across transplant settings. We propose practical, evidence-based guidelines for IR monitoring, including recommended time points, preferred assays, and flow cytometry panel components. Additionally, we highlight modifiable factors (e.g., immunosuppressive drug exposures, graft manipulation) offering interventional opportunities for influencing IR. Harmonized monitoring strategies will support robust correlation between IR and clinical outcomes, guide real-time risk stratification, and facilitate the development of targeted, individualized transplant approaches. Standardization efforts led by consortia and registries are essential for advancing knowledge and optimizing care. We provide a roadmap for implementing uniform IR monitoring to improve outcomes and quality of life for allo-HCT recipients.