CRP levels as a predictor of allogeneic transplant outcomes

Lia Minculescu and colleagues from Copenhagen University Hospital Rigshospitalet in Denmark conducted a retrospective study of allogeneic transplant patients to investigate whether C-reactive protein (CRP) levels drawn at time of graft-versus-host disease (GvHD) diagnosis can predict resistance to steroid therapy.

CRP is a protein made by the liver, which is released into the bloodstream as a response to tissue injury, infection or other inflammatory triggers. The study hypothesis is that co-existing causes of inflammation may aggravate GvHD. The study investigated both risk factors for development of GvHD and risk factors for development of steroid-refractory GvHD (SR-GvHD).

Key Findings:

• N = 461 total patients observed
  • Acute GvHD (aGvHD): 44%
  • Chronic GvHD (cGvHD): 49%
  • SR-GvHD: 6%
• Risk factors for GvHD grade II–IV
  • Age >53 years old vs < 53 years old: Odds Ratio (OR) = 0.67 (95% CI, 0.45–1.00), P = 0.05
  • Non-myeloablative prep regimen vs myeloablative: OR = 0.54 (95% CI, 0.36–0.8), P = 0.02
  • High-intensity (12 Gy) total body irradiation (TBI) vs other:OR = 0.35 (95% CI, 0.23–0.53), P = 0.001
  • Peripheral blood stem cell product vs bone marrow, OR = 0.63 (95% CI, 0.41–0.98), P = 0.04
• CRP levels at GvHD diagnosis
  • Liver: 104 mg/L (9–195)
  • Skin: 36 mg/L (0–223)
  • GI: 60 mg/L (0–253)
• Risk factors for SR-GVHD
  • Grade II vs III GVHD: OR = 0.05 (95% CI, 0.02–0.14), P = <0.001
  • Lack of visceral involvement: OR = 0.21 (95% CI, 0.09–0.51), P = 0.05
  • CRP >10: OR = 1.5 (95% CI, 1.18–1.93), P = 0.001
  • Patient age, preparatory regimen, TBI, donor-recipient gender mismatch, and graft source were not found to impact risk of SR-GvHD
• 5-year transplant related mortality (TRM) 50% greater if CRP >10 vs <10, P = 0.002
• GvHD-related mortality in SR-GvHD patients: 57.1%

This study showed that elevated CRP levels are associated with increased SR-GvHD and 5-year TRM rates. Grade III and visceral GvHD involvement also increased the risk of SR-GvHD. These are important indices that can help identify patients at highest risk of initial treatment failure to quickly navigate those patients toward second-line therapies.