Serum Protein Markers of Survival, Relapse and GvHD Identified within the First Two Weeks Post Stem Cell Transplantation

Allogeneic stem cell transplantation (SCT) is used widely in the treatment of hematopoietic malignancy. However, relapse of malignant disease and Graft vs host disease (GvHD) are primary causes of treatment failure and reflect a loss of immunological graft versus leukaemia effect. We measured the serum protein expression of 92 inflammation-related markers (by Olink Proteomics) from 49 patients at Day 0 (D0) and 154 patients at Day 14 (D14) following transplantation, relating these early serum protein levels to clinical outcomes including survival, relapse and GvHD risk. Numerous candidate biomarkers were identified with association to outcome. Specifically D14 serum expression of CDCP1, IL10 and PDL1 were elevated in all-cause mortality, CCL23 and LIFR increased in AGvHD and CASP8 increased in CGvHD. In contrast, levels of IL-2, IL-6 and IL-17C were decreased in patients who went on to suffer disease relapse. Time-to-event analysis revealed that serum concentration of CCL23 at D14 is predictive of short-term events including AGvHD, whilst CDCP1 is predictive of long-term events including the incidence of relapse-related mortality and overall survival. Increased serum expression of both CCL23 and CDCP1 at D14 were associated with worse patient prognosis. This work identifies potential biomarkers in the blood of SCT patients at very early post transplantation time points that could be utilised to inform treatment and early intervention decision making.

Kinsella:TC biopharm: Other: Data Safety and Monitoring Board ; Gilead: Research Funding; Therakos: Honoraria. Moss:astrazeneca: Research Funding.