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Immune profile differences between chronic GVHD and late acute GVHD: results of the ABLE/PBMTC 1202 studies

Schultz, K. R.; Kariminia, A.; Ng, B.; Abdossamadi, S.; Lauener, M.; Nemecek, E. R.; Wahlstrom, J. T.; Kitko, C. L.; Lewis, V. A.; Schechter, T.; Jacobsohn, D. A.; Harris, A. C.; Pulsipher, M. A.; Bittencourt, H.; Choi, S. W.; Caywood, E. H.; Kasow, K. A.; Bhatia, M.; Oshrine, B. R.; Flower, A.; Chaudhury, S.; Coulter, D.; Chewning, J. H.; Joyce, M.; Savasan, S.; Pawlowska, A. B.; Megason, G. C.; Mitchell, D.; Cheerva, A. C.; Lawitschka, A.; Azadpour, S.; Ostroumov, E.; Subrt, P.; Halevy, A.; Mostafavi, S.; Cuvelier, G. D. E.

Blood. 2020 Feb 13; 135(15):1287-1298

Abstract

Human graft-versus-host disease (GVHD) biology beyond 3 months after hematopoietic stem cell transplantation (HSCT) is complex. The Applied Biomarker in Late Effects of Childhood Cancer study (ABLE/PBMTC1202, NCT02067832) 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 post-HSCT and correlated with GVHD diagnosed according to the National Institutes of Health consensus criteria (NIH-CC) for cGVHD. Of 302 children enrolled, 241 were evaluable as L-aGVHD, cGVHD, active L-aGVHD or cGVHD, and no cGVHD/L-aGVHD. Significant marker differences, adjusted for major clinical factors, were defined as meeting all 3 criteria: receiver-operating characteristic area under the curve ≥0.60, P ≤ .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 immune profiles similar to NIH-CC. Both cGVHD and L-aGVHD had decreased transitional B cells and increased cytolytic natural killer (NK) cells. cGVHD had additional abnormalities, with increased activated T cells, naive helper T (Th) and cytotoxic T cells, loss of CD56bright regulatory NK cells, and increased ST2 and soluble CD13. Active L-aGVHD before day 114 had additional abnormalities in naive Th, naive regulatory T (Treg) cell populations, and cytokines, and active cGVHD had an increase in PD-1- and a decrease in PD-1+ 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 L-aGVHD and cGVHD. Further confirmation in adult and pediatric cohorts is needed.

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