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

doi:10.1182/BLOOD.2019003186

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 FlowerSonali 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

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

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 CD56^bright regulatory NK cells, and increased ST2 and soluble CD13. Active L-aGVHD before day 114 had additional abnormalities in naive Th, naive regulatory T (T_reg) cell populations, and cytokines, and active cGVHD had an increase in PD-12 and a decrease in PD-1¹ memory T_reg 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.

Original language	English (US)
Pages (from-to)	1287-1298
Number of pages	12
Journal	Blood
Volume	135
Issue number	15
DOIs	https://doi.org/10.1182/BLOOD.2019003186
State	Published - Apr 9 2020

Funding

A Canadian Institutes of Health Research team grant funded these studies. The team grant received funding from the Canadian Institutes of Health Research, the Canadian Cancer Society, the C17 Research Network, the Garron Family Cancer Center at the Hospital for Sick Children, and the Pediatric Oncology Group of Ontario. Support for PBMTC efforts was provided by a grant from the Johnny Crisstopher Children's Charitable Foundation St. Baldrick's Consortium as well as National Institutes of Health, National Heart, Lung, and Blood Institute/National Cancer Institute grant 2UG1HL069254. A Canadian Institutes of Health Research team grant funded these studies. The team grant received funding from the Canadian Institutes of Health Research, the Canadian Cancer Society, the C17 Research Network, the Garron Family Cancer Center at the Hospital for Sick Children, and the Pediatric Oncology Group of Ontario. Support for PBMTC efforts was provided by a grant from the Johnny Crisstopher Children’s Charitable Foundation St. Baldrick’s Consortium as well as National Institutes of Health, National Heart, Lung, and Blood Institute/National Cancer Institute grant 2UG1HL069254.

ASJC Scopus subject areas

Hematology
Biochemistry
Cell Biology
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1182/BLOOD.2019003186

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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., ... Cuvelier, G. D. E. (2020). Immune profile differences between chronic GVHD and late acute GVHD: Results of the ABLE/PBMTC 1202 studies. Blood, 135(15), 1287-1298. https://doi.org/10.1182/BLOOD.2019003186

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title = "Immune profile differences between chronic GVHD and late acute GVHD: Results of the ABLE/PBMTC 1202 studies",

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-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.",

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

note = "Publisher Copyright: {\textcopyright} 2020 by The American Society of Hematology",

year = "2020",

month = apr,

day = "9",

doi = "10.1182/BLOOD.2019003186",

language = "English (US)",

volume = "135",

pages = "1287--1298",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "15",

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Schultz, KR, Kariminia, A, Ng, B, Abdossamadi, S, Lauener, M, Nemecek, ER, Wahlstrom, JT, Kitko, CL, Lewis, VA, Schechter, T, Jacobsohn, DA, Harris, AC, Pulsipher, MA, Bittencourt, H, Choi, SW, Caywood, EH, Kasow, KA, Bhatia, M, Oshrine, BR, Flower, A, Chaudhury, S, Coulter, D, Chewning, JH, Joyce, M, Savasan, S, Pawlowska, AB, Megason, GC, Mitchell, D, Cheerva, AC, Lawitschka, A, Azadpour, S, Ostroumov, E, Subrt, P, Halevy, A, Mostafavi, S & Cuvelier, GDE 2020, 'Immune profile differences between chronic GVHD and late acute GVHD: Results of the ABLE/PBMTC 1202 studies', Blood, vol. 135, no. 15, pp. 1287-1298. https://doi.org/10.1182/BLOOD.2019003186

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.

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

Abstract

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UN SDGs

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