Allogeneic Haematopoietic Cell Transplants As Dynamical Systems: Influence of Early-term Immune Milieu on Long-term T-cell Recovery

Overview

Journal Clin Transl Immunology

Specialty Allergy & Immunology

Date 2023 Jul 17

PMID 37457614

Authors

Viktoriya Zelikson

Roy Sabo

Myrna Serrano

Younus Aqeel

Savannah Ward

Taha Al Juhaishi

May Aziz

Elizabeth Krieger

Gary Simmons

Catherine Roberts

Jason Reed

Gregory Buck

Amir Toor

Affiliations

Soon will be listed here.

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, = 11), or MMF given for 15 days with sargramostim (MMF15 arm, = 15). All patients underwent T-cell depletion with 5.1 mg kg 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.

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