Controlled, Randomized, Open-Label Trial of Risk-Stratified Corticosteroid Prevention of Acute Graft-Versus-Host Disease After Haploidentical Transplantation

J Clin Oncol. 2016 Jun 1;34(16):1855-63. doi: 10.1200/JCO.2015.63.8817. Epub 2016 Apr 18.

Abstract

Purpose: This study evaluated whether a prophylaxis strategy directed by the graft-versus-host disease (GVHD) biomarker might reduce the 100-day incidence of acute GVHD grades II to IV.

Patients and methods: This controlled, open-label, randomized trial included 228 patients who underwent haploidentical transplantation. On the basis of bone marrow allogeneic graft CD4:CD8 ratios, patients were categorized as low risk (n = 83; group A) or high risk (n = 145). Patients at high risk were randomly assigned to either receive (n = 72; group B) or not receive (n = 73; group C) low-dose corticosteroid prophylaxis.

Results: The incidence in group B was 21% (95% CI, 11% to 31%) compared with 26% (95% CI, 16%to 36%; P = .43) in group A and 48% (95% CI, 32% to 60%; P < .001) in group C. Low-dose corticosteroid prophylaxis was significantly associated with a relatively low risk of acute GVHD grades II to IV (hazard ratio, 0.66; 95% CI, 0.49 to 0.89; P = .007) and rapid platelet recovery (hazard ratio, 0.30; 95% CI, 0.23 to 0.47; P < .001). The incidence of moderate-to-severe chronic GVHD in group B (21%) was lower than that in both group A (50%; P = .025) and group C (36%; P = .066). The 100-day corticosteroid doses were 205 ± 111 mg in group B, 229 ± 149 mg in group A (P = .256), and 286.54 ± 259.67 mg in group C (P = .016). Compared with group C, group B showed significantly lower incidences of femoral head necrosis (P = .034) and hypertension (P = .015). Infection rates were comparable among these groups.

Conclusion: Our results suggest that risk stratification-directed, low-dose corticosteroid prophylaxis significantly decreased the incidence of acute GVHD grades II to IV, accelerated platelet recovery, and reduced adverse events without increasing infections.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Bone Marrow Transplantation / adverse effects*
  • Female
  • Graft vs Host Disease / prevention & control*
  • Hematopoiesis
  • Humans
  • Male
  • Middle Aged
  • Transplantation, Homologous

Substances

  • Adrenal Cortex Hormones