Unravelling a clinical role of peripheral blood leukemia stem cells at diagnosis in chronic myeloid leukemia patients: Final results of prospective FLOWERS study

Sicuranza, Anna;Pacelli, Paola;Santoni, Adele;Abruzzese, Elisabetta;Cattaneo, Daniele;Iurlo, Alessandra;Luciano, Luigiana;Galimberti, Sara;Giai, Valentina;Mulas, Olga;Caocci, Giovanni;Sorà, Federica;Capodanno, Isabella;Crugnola, Monica;Gozzini, Antonella;Russo, Sabina;Annunziata, Mario;Fozza, Claudio;Cartocci, Alessandra;Fredducci, Sara;Pacini, Emanuele;Liberati, Anna Marina;Defina, Marzia;Bestoso, Elena;Marzano, Cristina;Tocci, Dania;Miracapillo, Teresa;Turriziani, Camilla;Peccia, Katia;Raspadori, Donatella;Bocchia, Monica

2025-01-01

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Abstract

Background: The authors previously demonstrated that in peripheral blood (PB) of chronic myeloid leukemia (CML), patients’ leukemia stem cells (LSCs) CD26+ are detectable by flow cytometry at diagnosis, during tyrosine kinase inhibitor (TKI) therapy, and during treatment-free remission. Methods: This study presents results of a prospective multicenter study including 242 newly diagnosed CML patients monitored for PB CD26+ leukemic stem cells (LSCs) quantification from diagnosis up to 24 months of TKI treatment. Results: The bulk of CD26+ LSCs at diagnosis varied between patients with a median value of 7.14 cells/µL. During TKI treatment, it has been observed their consistent and rapid reduction without statistical differences according to type of first-line TKI. Instead, a significant correlation between a low amount of CD26+ LSCs at diagnosis and an optimal molecular response at 3, 12, and 24 months was documented (p =.03, p =.004, and p =.009, respectively). Three tertiles of CD26+ LSCs correlating to molecular response were identified: <3.21 cells/µL; between 3.21 and 19.21 cells/µL; and >19.21 cells/µL. The incidence of patients with optimal response was higher in the first CD26+ LSCs tertile respect to the third one (p =.027, p =.015, and p =.079, respectively) at all time points (3, 12 and 24 months). Conclusions: This study demonstrated a correlation between the amount of CD26+ LSCs at diagnosis and the molecular response, suggesting that the number of CD26+ LSCs at diagnosis could represent an additional tool for predicting TKI response.