Donor and Recipient Plasma Follistatin Levels are Associated with Acute Graft-versus-Host Disease in Blood and Marrow Transplant Clinical Trials Network 0402

Follistatin is an angiogenic factor elevated in the circulation after allogeneic hematopoietic cell transplantation (HCT). Elevations in follistatin plasma concentrations are associated with the onset of and poor survival after acute graft versus host disease (aGVHD). Using data from the Blood and Marrow Transplant Clinical Trials Network 0402 study (n=247), we sought to further quantify the longitudinal associations between plasma follistatin levels in transplant recipients, as well as baseline HCT donor follistatin levels, and allogeneic HCT outcomes. Higher recipient baseline follistatin levels were predictive of development of aGVHD (P=0.04). High donor follistatin levels were also associated with the incidence of aGVHD (P<0.01). Elevated follistatin levels on day 28 were associated with the onset of grade II–IV aGVHD prior to day 28, higher one-year non-relapse mortality, (NRM), and lower overall survival (OS). In multivariate analyses, individuals with follistatin levels >1088 pg/mL at day 28 had a four-fold increased risk for NRM (RR=4.3, 95% CI 1.9–9.9, P<0.01) and a nearly three-fold increased overall risk for mortality (RR=2.8, 95% CI 1.5–5.2, P<0.01). Given the multiple roles of follistatin in tissue inflammation and repair, and the confirmation that this biomarker is predictive of important HCT outcomes, the pathobiology of these relationships need further study.