Marionneaux, Steven Michael. The use of digital morphology for residual disease screening in patients with chronic lymphocytic leukemia. Retrieved from https://doi.org/doi:10.7282/t3-zpz5-dg38
DescriptionAdvancements in the treatment of chronic lymphocytic leukemia (CLL) have led to higher rates of complete remission (CR) and measurable residual disease (MRD) negativity. Currently, all patients who achieve CR are subsequently tested for MRD by high sensitivity multicolor flow cytometry (MFC also abbreviated FC). FC is expensive, time consuming, complicated and resource draining. Many patients in CR have higher levels of residual CLL lymphocytes that could be detected using a simpler screening test. The goal of the study was to determine if digital morphology (DM) review of peripheral blood films could fulfill this role and limit the use of FC to only those patients who test negative by DM. Blood films and FC results from 27 CLL patients in CR with various concentrations of CLL lymphocytes were studied. FC served as the reference method. To assist with the identification of CLL lymphocytes in these patients, the investigator and an independent expert examined images of numerous CLL lymphocytes from 40 randomly selected patients with active disease. From this review, criteria for CLL lymphocyte identification were developed that covered the morphologic variability that can be encountered between patients. The criteria were subsequently used in the method validation phase to identify CLL lymphocytes in the study patients during post-classification analysis and independent expert verification of the results. CLL lymphocytes were also presumptively identified using pre-classification data from the variant lymphocyte, plasma cell, blast and smudge cell results. A receiver operator characteristic curve was constructed to assess the diagnostic accuracy od DM. At an optimal threshold of 9.40% CLL lymphocytes, the sensitivity, specificity, and area under the curve were 36%, 100%, and .671 (p = .052). Additional statistical measurements of correlation and agreement between DM and FC were also calculated. Despite limitations associated with a small sample size and blood film artifacts, the findings of the study suggested it may be possible to use DM for morphologic identification of CLL lymphocytes. Incorporating the new DM test in the MRD decision tree algorithm may lead to more appropriate use of FC for MRD testing that is timelier and more cost effective.