Low serum complement C3 levels are associated with adverse clinical outcomes in myelodysplastic syndromes

Complement C3, a critical component of the complement system, has been implicated in cancer risk across various malignancies. However, its role in myelodysplastic syndromes (MDS) remains inadequately explored. This study investigates the impact of serum complement C3 levels on survival outcomes in patients with MDS.

Clinical data, including demographic characteristics (sex and age), hematological indices (white blood cell count and platelet count), bone marrow blast percentage, immunoglobulin levels (IgG, IgM, and IgA), and complement components (C3, C4, and Factor B), were retrospectively analyzed in 145 patients with MDS. Serum C3 levels were compared quantitatively between healthy controls and patients with MDS. Univariate and multivariate Cox proportional hazards regression analyses were employed to identify prognostic factors associated with clinical outcomes in MDS.

A significant reduction in peripheral blood complement C3 levels was observed in patients with MDS compared to healthy controls (P < 0.0001). Patients with lower serum C3 levels exhibited notably poorer clinical outcomes, including reduced overall survival (OS; P = 0.019) and leukemia-free survival (LFS; P = 0.043). Multivariate Cox regression analysis, incorporating the Revised International Prognostic Scoring System (IPSS-R) but not the Molecular IPSS (IPSS-M), identified serum C3 levels below 79 mg/dL as an independent prognostic factor for both OS (P = 0.041) and LFS (P = 0.005).

Decreased serum complement C3 levels emerge as an independent prognostic biomarker in MDS, correlating with unfavorable clinical outcomes regardless of IPSS-R stratification. This novel parameter offers additional prognostic value and may enhance existing risk assessment tools in the clinical management of MDS.