Early Hyperglycemia after Initiation of Glucocorticoid Therapy Predicts Adverse Outcome in Patients with Acute Graft-versus-Host Disease

Abstract

Because of first-line treatment with high-dose glucocorticoids (GC), steroid-induced hyperglycemia develops frequently in patients with acute graft-versus-host disease (aGVHD), potentially affecting their outcome. We performed a retrospective analysis on 104 patients who received systemic GC for aGVHD and investigated the consequences of aberrant glucose metabolism. In particular, we focused on glucose parameters early after initiation of GC. With a median of 50 (range, 4 to 513) blood glucose measurements during GC treatment, increasing mean, median, and maximum glucose levels and the need for insulin treatment were associated with decreased overall survival (OS) in simple and multiple survival analysis. Early hyperglycemia, as defined by mean blood glucose levels >125 mg/dL during the first 3 days of GC therapy, was also found to be highly associated with adverse outcome (hazard ratio [HR], 2.5 for death; 95% confidence interval [CI], 1.3 to 4.8, and HR of 3.5 for death due to nonrelapse mortality, 95% CI, 1.7 to 7.5, in a competing risk analysis). A score based on early hyperglycemia and nonresponse to GC within 7 days allowed the identification of 3 risk groups: patients with both risk factors had an inferior OS at 5 years of 4.1% compared with 75.4% in patients with none. Patients with 1 risk factor had a 5-year OS rate of 32.0% (P = .0002 for trend). Early hyperglycemia after GC initiation is a prominent risk factor for adverse outcome in patients with aGVHD. A score based solely on early hyperglycemia and lack of response to GC can predict survival in these patients.

Keywords: Acute graft-versus-host disease; Early hyperglycemia; Nonrelapse mortality; Overall survival; Steroid-induced hyperglycemia.