Buffy Coat Enrichment Improves the Success Rate of Conventional Cytogenetics in Hypocellular Specimens: A Prospective...

Background: Specimens with low cell counts may fail to yield sufficient analyzable metaphases or are rejected for chromosomal analysis. Buffy coat enrichment (BCE) concentrates nucleated cells prior to culture; however, its impact on routine cancer cytogenetics has not been systematically evaluated. Methods: We first validated BCE in hypocellular specimens (<5 K/µL) and then conducted a prospective quality improvement study from November 2024 to October 2025, encompassing 12,088 specimens. A phased intervention strategy was implemented by performing BCE on specimens with cell counts of 2.0-4.9 K/µL (designated as phase I); followed by expanding BCE to specimens with cell counts of 1.0-4.9 K/µL (phase II). Outcomes were assessed by the rate of successful karyotypes, defined as ≥10 analyzable metaphases. Results: In the validation cohort (cell counts < 5 K/µL), BCE improved the success rate across all cell count strata. In the prospective study cohort, implementation of BCE increased the overall success rate from 78% at baseline to 83% in phase I, and further increased to 90% in phase II. Conclusions: BCE significantly improves the success rate of chromosomal analysis by increasing the yield of metaphases in hypocellular specimens. This simple and scalable intervention reduces specimen rejection and enhances diagnostic yield in routine cancer cytogenetics.