Risk Factors for Severe Acute Graft-versus-Host Disease in Donor Graft Composition

Abstract

Acute graft-versus-host disease (aGVHD) is 1 of the main major complications of post-hematopoietic stem cell transplantation (HSCT). Identifying patients at risk of severe aGVHD may lead to earlier intervention and treatment, resulting in increased survival and a better quality of life. We aimed to identify biomarkers in donor grafts and patient plasma around the time of transplantation that might be predictive of aGVHD development. We build on our previously published methods by using multiplex assays and multicolor flow cytometry. We identified 5 easily assessable cellular markers in donor grafts that combined could potentially be used to calculate risk for severe aGVHD development. Most noteworthy are the T cell subsets expressing IL-7 receptor-α (CD127) and PD-1. Additionally, we identified a potential role for elevated tumor necrosis factor-α levels in both graft and patient before HSCT in development of aGVHD.

The importance of graft cell composition in outcome after allogeneic stem cell transplantation in patients with malignant disease

“…Our group has shown that additional precision in assessing patients outcome ie, risk for acute GVHD can be attained by pinpointing donor graft cell risk phenotypes, that is, PD-1 T-cells, their allogeneic reactivity in combination with biomarkers in the patients' plasma. 46,53…”

“…Our group has shown that additional precision in assessing patients outcome ie, risk for acute GVHD can be attained by pinpointing donor graft cell risk phenotypes, that is, PD-1 T-cells, their allogeneic reactivity in combination with biomarkers in the patients' plasma 46,53. In this single center study, there was a correlation between donor CD8 + cell dose and probability of relapse in the URD group while for patients with sibling PBSC donors, graft CD19 + and CD4 + cell dose were associated with acute and chronic GVHD, respectively.…”

Graft γδ TCR Sequencing Identifies Public Clonotypes Associated with Hematopoietic Stem Cell Transplantation Efficacy in Acute Myeloid Leukemia Patients and Unravels Cytomegalovirus Impact on Repertoire Distribution

“…PBSC samples were obtained during preparation of the graft for infusion and processed as previously described (3). Mononuclear cells were separated by density gradient centrifugation (800 g, 20 min, Lymphoprep; Fresenius Kabi, Oslo, Norway) and cryopreserved in liquid nitrogen in 10% DMSO in RPMI 1640 medium (HyClone; Thermo Fisher, Waltham, MA) enriched with 10% human AB-serum (Karolinska University Hospital), 100 IU/ml penicillin G (Life Technologies, Paisley, U.K.), and 100 mg/ml streptomycin (Life Technologies).…”

“…To improve transplantation outcomes, the impact of donor graft T cell subsets on the clinical outcome after HSCT has been studied. Although it has been clearly shown that ab T cells present in the grafts are the main component behind GvHD development (3)(4)(5)(6), little is known about gd T cells' influence on HSCT clinical outcomes.…”

The complex existence of γδ T cells following transplantation: the good, the bad and the simply confusing

“…Interestingly, the Foxp3‐positive subsets utilised both Vδ1 and Vδ2 TCR segments, and a follow‐up study narrowed the effective subset to be CD27 + Vδ1 + . However, in direct contrast, grafts containing higher proportion of CD8 + γδ T cells were associated with increased incidence of GvHD . Therefore, as reported in the above section, the role of γδ T cells in the prevention or promotion of GvHD following HSCT is far from clear.…”