Oral Presentation Australasian Cytometry Society 44th Annual Conference and Workshop

Measurable Residual Disease in Chronic Lymphocytic Leukaemia (24578)

Michelle Petrasich 1
  1. LabPlus, Auckland City Hospital, Auckland, New Zealand

In chronic lymphocytic leukaemia (CLL) measureable residual disease (MRD) has emerged as a
sensitive indicator of disease burden during and at the end of treatment, and provides prognostic
information. The detection of MRD above a level of 0.01% is an independent predictor of
progression-free-survival and overall-survival in CLL patients treated with chemoimmunotherapy.
Determining MRD status (by flow cytometric or molecular studies) is now an integral part of CLL
clinical trials, and there is evidence that using MRD as a surrogate of treatment depth response can
be used to assess the efficiency of new therapies.
With the increasing ability to achieve deeper remission it is suggested a lower level of MRD
assessment is required to measure residual disease, within a trial setting. International consensus
recommendations indicate that the use of an European-Research-Initiative on CLL (ERIC) compliant
flow cytometry assay of 6 or more colours, together with the acquisition of significantly more events
(2-5 million) permits an increased level of sensitivity, improving the level of detection to 0.001%.
With the entry of local patients into clinical trials the laboratory investigated the performance of a
dry format 8 colour tube: Duraclone® RE CLB (Beckman-Coulter), together with bulk lysis of either
peripheral blood or bone marrow, to quantify MRD in CLL to a lower level of detection of 0.001%.
Testing was performed on a FacsLyric flow cytometer (BD-Biosciences), and analysis undertaken
using Infinicyt software (Cytognos).
Statistical correlation between the existing flow cytometry assay, to a level of 0.01%, was acceptable
(R 2 = 0.9634), and dilution studies were performed to demonstrate detection between 0.01% and
0.001%.
While the role of MRD assessment in CLL is yet to be determined for routine clinical practice outside
of clinical trials, the laboratory is being asked to provide assays of increased sensitivity. With the
recent publication of the CLSI Flow Cytometry Validation document, this will be a challenging
process.

  1. Wierda WG, Rawstron AC, Cymbalista F, Badoux X, Rossi D, Brown JF et al. Measurable residual disease in chronic lymphocytic leukaemia: expert review and consensus recommendations. Leukaemia. 2021;35:3059-3072.
  2. Rawstron AC, Fazi C, Agathangelidis A, Villamor N, Letestu R et al. A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukaemia: an European Research Initiative on CLL study. Leukaemia. 2016. 30:929-936