Biomarkers for the detection of graft-versus-host disease in cancer patients after bone marrow transplantation

Sophie Paczesny

Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA

Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective form of tumor immunotherapy available to date, and the frequency of transplants continues to increase worldwide. However, while allogeneic HSCT can induce beneficial graft-versus-tumor (GVT) effects, the adverse effect of graft-versus-host disease (GVHD), which is closely linked to GVT, is the major source of morbidity and mortality following HSCT. Acute GVHD (aGVHD) develops when the donor's immune cells from the graft attack the patient's skin, liver, or intestines. Target organs involved in chronic GVHD (cGVHD) are variable, resemble autoimmune manifestations, and typically include skin; mucosa (mouth, eyes, genitalia); muscles/fascia/joints; lungs; and gastrointestinal tract/liver. GVHD occurs in two forms, classically distinguished as aGVHD, beginning before day 100 after HSCT, and cGVHD, occurring after day 100, although it is now accepted that these are two separate pathophysiologic entities. Currently available diagnostic and staging tools frequently fail to identify those at higher risk of GVHD progression, unresponsiveness to different forms of therapy, or death. Furthermore, there are shortcomings in the prediction of the future occurrence of GVHD before clinical signs develop. In parallel, in recent years there has been an explosive evolution of proteomics technologies, largely due to important advances in chemistry, engineering, high-throughput technical devices, and bioinformatics. Building on these opportunities, plasma biomarkers have been identified and validated both as promising diagnostic tools of GVHD and as prognostic tools for nonrelapse mortality. These biomarkers might facilitate timely and selective therapeutic intervention. However, such biomarkers should be more widely validated and incorporated into a new grading system to risk-stratify patients and better customize treatment. This review identifies biomarkers for the detection of GVHD; summarizes the current information on available GVHD biomarkers, which are mostly aGVHD biomarkers; proposes future prospects for the blinded evaluation of these biomarkers in samples collected as part of a multicenter prospective study; and discusses the need for biomarkers of cGVHD.

Keywords: GVHD, hematopoietic stem cell transplantation, risk stratification, proteomics