Key Points

  • Profiling of immune cell populations and plasma markers at day 100 after HSCT demonstrates biological differences between cGvHD and L-aGvHD

  • Immune profiling differences between patients meeting NIH diagnostic criteria versus those with distinctive features only were similar.

Human graft-versus-host disease (GvHD) biology beyond 3 months post-hematopoietic stem cell transplantation (HSCT) is complex. The Applied Biomarker in Late Effects of Childhood Cancer (ABLE/PBMTC1202, NCT02067832) study evaluated the immune profiles in chronic GvHD (cGvHD) and late acute GvHD (L-aGvHD). Peripheral blood immune cell and plasma markers were analyzed at day 100 after HSCT and correlated with GvHD diagnosed according to the NIH cGvHD consensus criteria (NIH-CC). Of 302 children enrolled, 241 were evaluable as a) L-aGvHD, b) cGvHD, c) active L-aGvHD or cGvHD, and d) no cGvHD/L-aGvHD. Significant marker differences, adjusted for major clinical factors, were defined as meeting all 3 criteria: ROC AUC ≥0.60; p-value ≤0.05; and effect ratio ≥1.3 or ≤0.75. Patients with only distinctive features but determined as cGvHD by the adjudication committee (non-NIH-CC) had similar immune profiles to NIH-CC. Both cGvHD and late aGvHD had decreased transitional B cells and increased cytolytic NK cells. cGvHD had additional abnormalities, with increased activated T cells, naïve Th and Tc cells, a loss of CD56bright NKreg cells; and increased ST2 and sCD13. Active L-aGvHD before day 114 had additional abnormalities in naïve Th, naive Treg populations, and cytokines and active cGvHD an increase in PD-1- and decrease in PD1+ memory Treg cells. Unsupervised analysis appeared to show a progression of immune abnormalities from no cGvHD/L-aGvHD to L-aGvHD with the most complex pattern in cGvHD. Comprehensive immune profiling will allow us to better understand how to minimize late aGvHD and cGvHD. Further confirmation in adult and pediatric cohorts are needed.

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