Immune profile differences between chronic GVHD and late acute..

TRANSPLANTATION| APRIL 9, 2020

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

Kirk R. Schultz, Amina Kariminia, Bernard Ng, Sayeh Abdossamadi, Madeline Lauener, Eneida R. Nemecek, Justin T. Wahlstrom, Carrie L. Kitko, Victor A. Lewis, Tal Schechter, David A. Jacobsohn, Andrew C. Harris, Michael A. Pulsipher, Henrique Bittencourt, Sung Won Choi, Emi H. Caywood, Kimberly A. Kasow, Monica Bhatia, Benjamin R. Oshrine, Allyson Flower, Sonali Chaudhury, Donald Coulter, Joseph H. Chewning, Michael Joyce, Sureyya Savasan, Anna B. Pawlowska, Gail C. Megason, David Mitchell, Alexandra C. Cheerva, Anita Lawitschka, Shima Azadpour, Elena Ostroumov, Peter Subrt, Anat Halevy, Sara Mostafavi, Geoffrey D. E. Cuvelier

Blood (2020) 135 (15): 1287–1298.

https://doi.org/10.1182/blood.2019003186

Key Points

Profiling of immune cell populations and plasma markers at day 100 post-HSCT demonstrates biological differences between cGVHD and L-aGVHD.

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

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.

Subjects:

Clinical Trials and Observations, Immunobiology and Immunotherapy, Transplantation

Topics:

graft-versus-host disease, chronic, graft-versus-host disease, acute

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