Allogeneic haematopoietic cell transplants as dynamical systems: influence of early-term immune milieu on long-term T-cell recovery.
OBJECTIVES: Immune recovery following haematopoietic cell transplantation (HCT) functions as a dynamical system. Reducing the duration of intense immune suppression and augmenting antigen presentation has the potential to optimise T-cell reconstitution, potentially influencing long-term outcomes.
METHODS: Based on donor-derived T-cell recovery, 26 patients were adaptively randomised between mycophenolate mofetil (MMF) administered for 30-day post-transplant with filgrastim for cytokine support (MMF30 arm,
RESULTS: Clinical outcomes were equivalent between the two groups. The MMF15 arm demonstrated superior T-cell, as well as T-cell subset recovery and a trend towards superior T-cell receptor (TCR) diversity in the first month with this difference persisting through the first year. T-cell repertoire recovery was more rapid and sustained, as well as more diverse in the MMF15 arm.
CONCLUSION: The long-term superior immune recovery in the MMF15 arm, administered GMCSF, is consistent with a disproportionate impact of early interventions in HCT. Modifying the 'immune-milieu' following allogeneic HCT is feasible and may influence long-term T-cell recovery.
Published In/Presented At
Zelikson, V., Sabo, R., Serrano, M., Aqeel, Y., Ward, S., Al Juhaishi, T., Aziz, M., Krieger, E., Simmons, G., Roberts, C., Reed, J., Buck, G., & Toor, A. (2023). Allogeneic haematopoietic cell transplants as dynamical systems: influence of early-term immune milieu on long-term T-cell recovery. Clinical & translational immunology, 12(7), e1458. https://doi.org/10.1002/cti2.1458
Medicine and Health Sciences
Department of Medicine, Hematology-Medical Oncology Division