Anti-Thymocyte Globulin Prophylaxis Induces a Decrease in Naive Th Cells to Inhibit the Onset of Chronic Graft-versus-Host Disease: Results from the Canadian Bone Marrow Transplant Group (CBMTG) 0801 Study

Leonie Naeije; Amina Kariminia; Sayeh Abdossamadi; Shima Azadpour; Peter Subrt; Boris Kuzeljevic; Michael A Irvine; Irwin Walker; Kirk R Schultz

doi:10.1016/j.bbmt.2019.11.015

Anti-Thymocyte Globulin Prophylaxis Induces a Decrease in Naive Th Cells to Inhibit the Onset of Chronic Graft-versus-Host Disease: Results from the Canadian Bone Marrow Transplant Group (CBMTG) 0801 Study

Biol Blood Marrow Transplant. 2020 Mar;26(3):438-444. doi: 10.1016/j.bbmt.2019.11.015. Epub 2019 Nov 19.

Authors

Leonie Naeije¹, Amina Kariminia², Sayeh Abdossamadi², Shima Azadpour³, Peter Subrt², Boris Kuzeljevic⁴, Michael A Irvine⁴, Irwin Walker⁵, Kirk R Schultz⁶

Affiliations

¹ Division of Pediatric Hematology/Oncology/Blood & Marrow Transplant, BC Children's Hospital, Vancouver, British Columbia, Canada.
² Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
³ Department of Hematology, Faculty of Medical Sciences, Tarbiat Modaress University, Tehran, Iran.
⁴ Clinical Research Support Unit, BC Children's Research, Vancouver, British Columbia, Canada.
⁵ McMaster University and Juravinski Hospital and Cancer Centre, Hamilton, Ontario, Canada.
⁶ Division of Pediatric Hematology/Oncology/Blood & Marrow Transplant, BC Children's Hospital, Vancouver, British Columbia, Canada; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada. Electronic address: kschultz@mail.ubc.ca.

PMID: 31756535
DOI: 10.1016/j.bbmt.2019.11.015

Abstract

Anti-thymocyte globulin (ATG) is an established approach to decrease chronic GVHD (cGVHD), yet the exact mechanism is uncertain. To better understand the mechanism of action of ATG in preventing cGVHD, we evaluated the day 100 immune reconstitution of known cGVHD cellular biomarkers using patients from the randomized Canadian Bone Marrow Transplant Group (CBMTG) 0801 trial, which demonstrated a significant impact of ATG on cGVHD. In a separate companion biology study, we evaluated the impact of ATG prophylaxis on cGVHD cellular markers at day 100 in 40 CBMTG 0801 patients. Analysis focused on previously identified cGVHD cellular biomarkers, including naive helper T (Th) cells, recent thymic emigrant (RTE) Th cells, CD21^low B cells, CD56^bright NK_reg cells, and T_reg cells ST2, osteopontin, soluble B-cell activating factor (sBAFF), Interleukin-2 receptor alpha (sCD25), T-cell immunoglobulin and mucin domain-3 (TIM-3), matrix metallopeptidase 3, ICAM-1, C-X-C motif chemokine 10 (CXCL10), and soluble aminopeptidase N. The ATG-treated group had a >10-fold decrease in both RTE naive Th and naive Th cells (P < .0001) and a 10-fold increase in CD56^bright NK_reg cells (P < .0001). T_reg cells, conventional Th cells, CD21^low B cells, and all plasma markers were not affected. In the populations most affected by ATG, changes in naive Th cells were associated with the later development of cGVHD. This analysis suggests that ATG primarily impacts on cGVHD through suppression of naive Th cell expansion after transplantation. These associations need to be validated in additional studies.

Trial registration: ClinicalTrials.gov NCT01217723.

Keywords: ATG; Biomarkers; Development cGVHD; Hematopoietic stem cell transplantation; Naive Th cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antilymphocyte Serum / therapeutic use
Canada
Graft vs Host Disease* / prevention & control
Hematopoietic Stem Cell Transplantation*
Humans
Transplantation Conditioning

Substances

Antilymphocyte Serum

Associated data

ClinicalTrials.gov/NCT01217723

Grants and funding

CIHR/Canada