Proteomics in the discovery of biomarkers of major complications after allogeneic hematopoietic cell transplantation.

PURPOSE OF REVIEW: Allogeneic hematopoietic cell transplantation (allo-HCT) is complicated by life-threatening conditions whose prompt diagnosis is essential yet frequently delayed. This review examines proteomic approaches to biomarker discovery for the most common posttransplant complications, emphasizing methodological reliability and translational status. RECENT FINDINGS: Proximity extension assay (PEA) and aptamer-based platforms now permit simultaneous quantification of thousands of proteins from microliter plasma volumes. For acute graft-versus-host disease (GVHD), validated plasma panels incorporating ST2 and REG3α have been established as prognostic tools, and a PEA discovery study in patients with acute myeloid leukemia identified a four-marker panel (SLAMF7, IL-1ra, BTN3A2, and DAB2) with an area under the curve of 0.90. For sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), a PEA study of very severe cases identified multiple candidate proteins at diagnosis and four proteins whose serum levels declined during defibrotide treatment. Proteomic evidence for other complications remains sparse and early in development. SUMMARY: Most proteomic biomarker studies in allo-HCT derive from small single-center discovery cohorts. Multicenter validation, harmonized biobanking, and integration with clinical risk models are required before these biomarkers can enter transplant practice.