Allogeneic haematopoietic cell transplants as dynamical systems: influence of early‐term immune milieu on long‐term T‐cell recovery

Abstract

Abstract 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, N = 11), or MMF given for 15 days with sargramostim (MMF15 arm, N = 15). All patients underwent in vivo T‐cell depletion with 5.1 mg kg−1 antithymocyte globulin (administered over 3 days, Day −9 through to Day −7) and received reduced intensity 450 cGy total body irradiation (3 fractions on Day −1 and Day 0). Patients underwent HLA‐matched related and unrelated donor haematopoietic cell transplantation (HCT). 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.

Keywords

• graft versus host disease
• haematopoietic cell transplantation
• immune reconstitution
• T‐cell receptor beta repertoire
• T‐cell recovery
• total body irradiation