Bone marrow fibrosis at diagnosis predicts survival for primary acute myeloid leukemia.

Abstract

As a desmoplastic reaction, tissue fibrosis played crucial roles in solid tumor progression, chemo-resistance, and consequently heralded poor clinical outcome. Previous studies implied the effects of marrow fibrosis on prognosis for acute lymphoblastic leukemia were disputable. In this study, we aimed to investigate the potential role of bone marrow fibrosis on clinical survival in acute myeloid leukemia (AML) patients. Bone marrow fibrosis (evaluated as reticulin fiber density, RFD) in bone marrow sections was evaluated at diagnosis via computer technology. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of RFD for relapse and survival status. Kaplan-Meier method was used to estimate survival rates per subgroup between patients with different RFD. Cox proportional hazard regression was used to model the overall survival. High RFD at diagnosis in bone marrow sections from primary AML might predict early relapse and shorter survival (P=0.003 and 0.001, respectively). The optimal cutoff value of RFD at diagnosis was determined to be 7.2%. Furthermore, the Kaplan-Meier analysis indicated that patients with high marrow RFD had shorter relapse-free survival (RFS) and overall survival (OS) than patients with low RFD (P=0.007 and 0.000, respectively). Multivariate analysis suggested that similar with cytogenetics, marrow RFD at diagnosis was an independent prognostic factor for RFS [HR 0.564, 95% confidence interval (CI) 0.338-0.940, P=0.028] and OS (HR 0.457, 95% CI 0.225-0.929, P=0.031) in primary AML patients. Our data suggest that marrow RFD before treatment should be seemed as prognostic factor in primary AML, it may provide valuable clues for developing new targeted therapy.