Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia

Abstract

Treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors has advanced to a stage where many patients achieve very low or undetectable levels of disease. Remarkably, some of these patients remain in sustained remission when treatment is withdrawn, suggesting that they may be at least operationally cured of their disease. Accurate definition of deep molecular responses (MRs) is therefore increasingly important for optimal patient management and comparison of independent data sets. We previously published proposals for broad standardized definitions of MR at different levels of sensitivity. Here we present detailed laboratory recommendations, developed as part of the European Treatment and Outcome Study for CML (EUTOS), to enable testing laboratories to score MR in a reproducible manner for CML patients expressing the most common BCR-ABL1 variants.

Figure 1

LoD of BCR-ABL1 detection. The graph shows the Poisson distribution with a mean of 3 BCR-ABL1 targets per well. The percentage of wells with 0–10 targets per well is indicated (20  000 computer-generated random datapoints; Minitab version 16, Coventry, UK) and shows that 95% of wells has at least one BCR-ABL1 target. As the LoD is defined as the lowest concentration of target that can be detected with 95% confidence, the maximal theoretical LOD is 3 copies.