Lineage-specific detection of residual disease predicts relapse in chronic myeloid leukemia patients stopping therapy.

Chronic myeloid leukemia (CML) patients who are eligible for treatment-free remission (TFR) may still relapse after tyrosine kinase inhibitor (TKI) cessation. There is a need for accurate predictors of outcome to enable patients with a favorable profile to proceed while avoiding futile attempts. Sensitive detection of residual disease in total leukocytes at treatment cessation is associated with relapse, but is not highly discriminatory, likely because it is a composite measure of residual leukemia derived from different cell lineages whereas only some lineages are relevant for relapse. We prospectively measured BCR::ABL1 DNA as a predictive yes/no binary test in five cellular fractions from 48 patients meeting conventional criteria for TKI discontinuation. The median BCR::ABL1 DNA level was higher in granulocytes and in T cells, but not in other lineages, in patients who relapsed. In the 40 patients undergoing a first TFR attempt we defined three groups with differing relapse risk: granulocytes-positive (100%), granulocytes-negative/T cells-positive (67%), and granulocytes-negative /T cells-negative (25%). These data show the critical importance of lineage-specific assessment of residual disease in the selection of patients who can attempt TFR with a high expectation of success, and concurrently defer patients who have a high probability of relapse.