Lia Minculescuand colleagues from Copenhagen University Hospital Rigshospitaletin 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) vsother:OR = 0.35 (95% CI, 0.23–0.53), P= 0.001
- Peripheral blood stem cell product vsbone 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 vsIII 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.