Leukemic stem cells shall be searched in the bone marrow before "tyrosine kinase inhibitor-discontinuation" in chronic myeloid leukemia.

Abstract

Leukemic stem cells (LSCs) of chronic myeloid leukemia (CML), persisting in the bone marrow (BM) niche, could be responsible for the relapses within the patients of whom the treatment-free remission (TFR) had been attempted. We assessed the presence of the CML LSCs in the peripheral blood (PB) and concurrently in the BM in the patients with chronic-phase CML (CP CML). Thirty-eight patients with CP CML were included into the study. CD45+ /CD34+ /CD38- cells with positive CD26 expression were considered as CML LSCs (CD26+ LSC) by using multiparameter flow cytometry (FCM). Mean BCR-ABL, PB LSC, and BM LSC were 58.528 IS (37.405-83.414 IS), 237.5LSC/μL (16-737.5LSC/μL), and 805LSC/106 WBCs (134.6-2470LSC/106 WBCs), respectively, in newly diagnosed CML patients. In the patients with BCR-ABL positive hematopoiesis, mean BCR-ABL, PB LSCs, and BM LSCs were 30.09IS (0.024-147.690IS), 13.5LSC/μL (0-248.7LSC/μL) and 143.5LSC/106 WBCs (9-455.2LSC/106 WBCs), respectively. No CML LSCs were detected in PB of patients who achieved deep molecular response (DMR). BM LSCs of the patients who were in DMR were 281.1LSC/106 WBCs (3.1-613.7LSC/106 WBCs). The amount of PB LSCs was highest in patients with newly diagnosed CML (P<.001). LSCs persisted in the BM of the patients with DMR, whereas there was no LSCs in the peripheral blood. The investigation of the CML LSCs in bone marrow before deciding TKI discontinuation could be justified to achieve and maintain stable TFR.