B08 | Clinical role of peripheral blood leukemia stem cells at diagnosis in chronic myeloid leukemia: final results of the Prospective Flowers Study

Background: We previously demonstrated that CD26+ leukemia stem cells (LSCs) are detectable by flow cytometry in the peripheral blood (PB) of chronic myeloid leukemia (CML) patients (pts) at diagnosis, during tyrosine kinase inhibitor (TKI) therapy, and in treatment-free remission (TFR). However, prospective data on the dynamics of PB CD26+LSCs from diagnosis and their potential correlation with molecular response (MR) are lacking.Methods: We report final results of a prospective, multicenter Italian study enrolling newly diagnosed chronic phase (CP) CML. Pts were centrally monitored by flow cytometry to quantify PB CD26+LSCs from diagnosis up to 24 months (mos) of therapy.Results: 242 consecutive CP-CML pts were included (132 treated with imatinib, 72 with nilotinib, and 38 with dasatinib). The CD26+LSC count at diagnosis varied among pts, with a median of 7.14 cells/µl (IQR 2.18–33.26 cells/µl). During TKI, we observed a rapid and significant reduction of CD26+LSCs, with median values decreasing to 0.013 cells/µL (IQR 0–0.034), 0.011 cells/µL (IQR 0–0.031), and 0.007 cells/µL (IQR 0–0.025) at 3, 12, and 24 mos, respectively. No significant differences in LSC log-reduction were observed according to the type of TKI employed. CD26+LSCs were significantly higher in the high Sokal risk group compared to intermediate or low risk groups (22.65 cells/µL vs 5.60 cells/µL vs 6.16 cells/µL) (p=0.018). A significant association was found between low CD26+LSCs count at diagnosis and optimal MR (BCR::ABL1