Prognosis in Pediatric Hematologic Malignancies Is Associated With Serum Concentration of Mannose-Binding Lectin-Associated Serine Protease-2 (MASP-2)

Background. Mannose-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are key components of the lectin pathway of complement activation. Their serum concentrations show a wide interindividual variability. This study investigated whether the concentration of MBL and MASP-2 is associated with prognosis in pediatric patients with cancer. Methods. In this retrospective multicenter study, MBL and MASP-2 were measured by commercially available ELISA in frozen remnants of serum taken at diagnosis. Associations of overall Survival (OS) and event-free survival (EFS) with MBL and MASP-2 were assessed by multivariate Cox regression accounting for prognostically relevant clinical variables. Results. in the 372 patients studied, median serum concentration of MBL was 2,808 mu g/L (range, 2-10,060) and 391 mu g/L (46-2,771) for MASP-2. The estimated 4-year EFS was 0.60 (OS, 0.78). In the entire, heterogeneous sample, MBL and MASP-2 were not significantly associated with OS or EFS. In patients with hematologic malignancies, however, higher MASP-2 was associated with better EFS in a significant and clinically relevant way (hazard ratio per tenfold increase (HR), 0.22; 95% Cl, 0.09-0.54; P=0.001). This was due to patients with lymphoma (HR, 0.11; 95% Cl, 0.03-0.47; P=0.003), but less for those with acute leukemia (HR, 0.35; 95% Cl, 0.11-1.15; P=0.083). Conclusion. In this study, higher MASP-2 was associated with better EFS in pediatric patients with hematologic malignancies, especially lymphoma. Whether MASP-2 is an independent prognostic factor affecting risk stratification and anticancer therapy needs to be assessed in prospective, disease-specific Studies. Pediatr Blood Cancer 2009;53:53-57. (C) 2009 Wiley-Liss, Inc.