Clustered precursors in bone marrow sections predict early relapse in patients with acute myeloid leukemia within hematologic remission

BACKGROUND: Bone marrow (BM) aspiration is largely used for relapse assessment in acute myeloid leukemia (AML). It remains unclear what roles that BM trephine biopsy plays on relapse assessment. METHODS: Bone marrow (BM) sections during complete remission (CR) from 60 acute myeloid leukemia (AML) patients were retrospectively analyzed. Computer image processing technology was performed for detection of the distance between precursors and endosteum, and density of precursors was also calculated under light microscopic image. Immunohistochemistry was used to identify the immunophenotype of clustered precursors. RESULTS: Except for single and double precursors, there existed clustered precursors of 3-5 cells during CR. Here, we demonstrated that clustered precursors, but not single and double precursors, were useful in risk factor of relapse. Area under the receiving operator curve (ROC) was of 0.007 (CI 95%, from 0.572 to 0.851). Using a standard cut-off value of >4.0/mm(2) for cluster density, early relapse was detected with a sensitivity of 51.5% and a specificity of 85.7%. Multivariate Cox regression analysis revealed that clustered precursor is an independent risk factor for early relapse (Adjusted HR: 0.325, 95% CI: 0.156-0.679, p = 0.003). CONCLUSIONS: Cumulatively, clustered precursors in BM sections during CR may serve as an independent risk factor of early relapse and poor outcome for AML patients in cluster density > 4.0/mm(2) in sections. Early aggressive interventions are needed to prevent hematologic relapse.