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Prognosis in pediatric hematologic malignancies is associated with serum concentration of mannose-binding lectin-associated serine protease-2 (MASP-2)

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Abstract

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 µg/L (range, 2–10,060) and 391 µg/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% CI, 0.09–0.54; P = 0.001). This was due to patients with lymphoma (HR, 0.11; 95% CI, 0.03–0.47; P = 0.003), but less for those with acute leukemia (HR, 0.35; 95% CI, 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. © 2009 Wiley-Liss, Inc.

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