Leukemic stem cells shall be searched in the bone marrow before “tyrosine kinase inhibitor‐discontinuation” in chronic myeloid leukemia

Abstract

Background 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). Patients and Methods 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). Results Mean BCR‐ABL, PB LSC, and BM LSC were 58.528 IS (37.405‐83.414 IS), 237.5 LSC/μL (16‐737.5 LSC/μL), and 805 LSC/106 WBCs (134.6‐2470 LSC/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 30.09 IS (0.024‐147.690 IS), 13.5 LSC/μL (0‐248.7 LSC/μL) and 143.5 LSC/106 WBCs (9‐455.2 LSC/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 281.1 LSC/106 WBCs (3.1‐613.7 LSC/106 WBCs). The amount of PB LSCs was highest in patients with newly diagnosed CML (P < .001). Conclusion 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.

Identification of peripheral blood CD26+ leukemic stem cells has a potential role in the rapid diagnosis of chronic myeloid leukemia

“…They concluded that TKIs are ineffective in eliminating the CD26+ CML LSCs from bone marrow even in patients who had DMR. 9 In the present cohort, all the patients with a documented RTPCR-negative result had undetectable CD26+ LSCs in the PB. BM results were not available in these patients.…”

“…A recent study on 38 CML‐CP patients on TKIs with a documented deep molecular response (DMR) found persisting CD26+ CML LSCs in the bone marrow, whereas circulating LSCs were not found. They concluded that TKIs are ineffective in eliminating the CD26+ CML LSCs from bone marrow even in patients who had DMR 9 . In the present cohort, all the patients with a documented RTPCR‐negative result had undetectable CD26+ LSCs in the PB.…”

Peripheral blood CD26 positive leukemic stem cells as a possible diagnostic and prognostic marker in chronic myeloid leukemia

“…However, treatment can be successfully discontinued in a minority of patients depending on whether the durations of both treatment and DMR are long enough to make TFR a feasible option [ 26 ]. Other authors recommended BM examination for LSC before the discontinuation of TKI treatment [ 27 ].…”

CD26/DPP-4 in Chronic Myeloid Leukemia

“…A recent work of a Turkish group on 38 CML patients showed that CD26+ LSCs were fluctuating but measurable, both in PB and BM samples, during TKI treatment. However, in those CML patients in DMR, CD26+ LSCs were present in BM but not in PB samples [ 54 ]. These findings, even if based on a small cohort of patients evaluated, once again open the controversial question about the appropriateness of PB and/or BM samples for measuring residual CD26+ LSCs.…”