Biomarkers for Allogeneic HCT Outcomes

Abstract

Allogeneic hematopoietic cell transplantation (HCT) remains the only curative therapy for many hematological malignant and non-malignant disorders. However, key obstacles to the success of HCT include graft-versus-host disease (GVHD) and disease relapse due to absence of graft-versus-tumor (GVT) effect. Over the last decade, advances in "omics" technologies and systems biology analysis, have allowed for the discovery and validation of blood biomarkers that can be used as diagnostic test and prognostic test (that risk-stratify patients before disease occurrence) for acute and chronic GVHD and recently GVT. There are also predictive biomarkers that categorize patients based on their likely to respond to therapy. Newer mathematical analysis such as machine learning is able to identify different predictors of GVHD using clinical characteristics pre-transplant and possibly in the future combined with other biomarkers. Biomarkers are not only useful to identify patients with higher risk of disease progression, but also help guide treatment decisions and/or provide a basis for specific therapeutic interventions. This review summarizes biomarkers definition, omics technologies, acute, chronic GVHD and GVT biomarkers currently used in clinic or with potential as targets for existing or new drugs focusing on novel published work.

Management of Chronic Graft-vs.-Host Disease in Children and Adolescents With ALL: Present Status and Model for a Personalised Management Plan

“…Among those considered to be validated plasma biomarkers are soluble BAFF, a panel consisting of 4 biomarkers [ST2, chemokine (C-X-C) motif ligand 9 (CXCL9), matrix metalloproteinase 3 (MMP-3) and osteopontin], CXCL10, and chemokine (C-C motif) ligand 15 (CCL15) (Table 1) (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63). Validated cellular biomarkers include CD163, B cells expressing toll-like receptor 9 (TLR9), B cells defined as CD19 + /CD21 low B cells, a high BAFF:B cell ratio in the plasma, T regs , CD4 + CD146 + CCR5 + T cells and Tfh cells (Table 1) (64). We briefly discuss these biomarkers below.…”

Enzymatic Methods for Salivary Biomarkers Detection: Overview and Current Challenges

“…A biomarker, also known as a biological marker, is any molecule, substance, or measurable process in the body or in one of its components that can support the diagnosis, prognosis, prediction, or response to the treatment of a disease [1]. Unlike symptoms, which often are endpoints of the disease, biomarkers appear, disappear, or vary in concentration from the onset of the disease, so they are useful for detection at earlier stage [2].…”

Acute GVHD: think before you treat

“…In addi tion to opti miz ing clin i cal GVHD scor ing sys tems, efforts to improve the deter mi na tion of sever ity and like li hood of re sponse have focused on iden ti fy ing periph eral blood bio mark ers. Criteria and phases of bio marker devel op ment, as well as the dif fer ent types of bio mark ers for acute and chronic GVHD, have recently been reviewed by Adom et al 13 Because some avail able bio mark ers used to diag nose aGVHD are con founded by organ dam age or infec tions, they are of lim ited use in aGVHD risk assess ment.…”