Detection of Dormant Chronic Myeloid Leukemia Clones in the Bone Marrow of Patients in Complete Molecular Remission

Clonogenic assays have been proposed as a means to document the absence of minimal residual disease (MRD) in chronic myeloid leukemia (CML) with the intent of treatment discontinuation. A pilot study in 14 patients in chronic phase indicates that clonogenic assays are not sensitive enough to confidently document the absence of MRD. Background: Several methods are available to detect MRD in patients with CML in complete molecular remission (CMR) and taking tyrosine kinase inhibitor (TKI) therapy. Materials and Methods: We performed clonogenic assays on mononuclear bone marrow cells from 14 patients. Of the 10 assessable samples, 6 were from patients in CMR and 4 from patients in complete cytogenetic remission but had detectable MRD using polymerase chain reaction (FOR) analysis (positive controls). At least 10 colonies per sample were microaspirated and individual colonies were subjected to FOR analysis. Results: Of the 6 patients in CMR, 5 harbored breakpoint cluster region abelson (BCR-ABL1) negative colonies but in 1 sample, 1 of the 10 colonies analyzed was positive for BCR-ABL1. Of the 4 patients with evidence of MRD in peripheral blood, 2 had negative and 2 had positive BCR-ABL1 colonies. Conclusion: MRD is still detectable using clonogenic assays in some patients with CML after achieving CMR using TKI therapy, which is likely responsible for relapse on TKI discontinuation. Because of the large number of single colonies that need to be analyzed, the use of clonogenic assays in clinical practice to determine the feasibility of TKI discontinuation is not recommended.