TY - JOUR
T1 - Immune profile differences between chronic GVHD and late acute GVHD
T2 - Results of the ABLE/PBMTC 1202 studies
AU - Schultz, Kirk R.
AU - Kariminia, Amina
AU - Ng, Bernard
AU - Abdossamadi, Sayeh
AU - Lauener, Madeline
AU - Nemecek, Eneida R.
AU - Wahlstrom, Justin T.
AU - Kitko, Carrie L.
AU - Lewis, Victor A.
AU - Schechter, Tal
AU - Jacobsohn, David A.
AU - Harris, Andrew C.
AU - Pulsipher, Michael A.
AU - Bittencourt, Henrique
AU - Choi, Sung Won
AU - Caywood, Emi H.
AU - Kasow, Kimberly A.
AU - Bhatia, Monica
AU - Oshrine, Benjamin R.
AU - Flower, Allyson
AU - Chaudhury, Sonali
AU - Coulter, Donald
AU - Chewning, Joseph H.
AU - Joyce, Michael
AU - Savasan, Sureyya
AU - Pawlowska, Anna B.
AU - Megason, Gail C.
AU - Mitchell, David
AU - Cheerva, Alexandra C.
AU - Lawitschka, Anita
AU - Azadpour, Shima
AU - Ostroumov, Elena
AU - Subrt, Peter
AU - Halevy, Anat
AU - Mostafavi, Sara
AU - Cuvelier, Geoffrey D.E.
N1 - Publisher Copyright:
© 2020 by The American Society of Hematology
PY - 2020/4/9
Y1 - 2020/4/9
N2 - 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-12 and a decrease in PD-11 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.
AB - 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-12 and a decrease in PD-11 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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U2 - 10.1182/BLOOD.2019003186
DO - 10.1182/BLOOD.2019003186
M3 - Article
C2 - 32047896
AN - SCOPUS:85084987345
SN - 0006-4971
VL - 135
SP - 1287
EP - 1298
JO - Blood
JF - Blood
IS - 15
ER -