Increased NK Cells and Decreased CD3+CD8+CD62L+ T Cells in CML Patients Who Sustained Complete Molecular Remission After Discontinuation of Imatinib
Authors: Ohyashiki Kazuma , Katagiri Sei-ichiro , Tauchi Tetsuzo , Ohyashiki Junko H , Maeda Yasuhiro , Matsumura Itaru , Kyo Taiichi 
Published: October 2019

Abstract
Abstract 1697

Background and Aim:
Recent study demonstrated that approximately 60% of chronic myeloid leukemia (CML) patients who stopped imatinib therapy (STOP-IM) after a period of stable complete molecular remission (CMR) relapsed molecularly within the next 6 months, whereas nearly all the remaining patients sustained a stable CMR beyond 18 months of follow-up.

Study design:
To elucidate the immunological diversity of CML patients, we assessed subsets of circulating lymphocytes obtained from 30 CML patients: 16 CML patients who had discontinued imatinib treatment for more than 6 months (STOP-IM), and 14 CML patients who were receiving imatinib with CMR for more than 2 consecutive years.

Results:
One-way analysis of variance revealed that certain cell fractions of lymphocyte subsets were significantly altered in STOP-IM patients compared with healthy volunteers and CML-CMR patients. We focused on the CD3+CD8+CD62L+ and CD3―CD56+ cell fractions, because other cell fractions, except CD19+CD20+, were not particularly different between STOP-IM and CML-CMR patients. The CD3+CD8+CD62L+ cell fractions in STOP-IM patients tended to down-regulate (P = 0.0658) and the CD3―CD56+ cell fraction increased significantly compared with that in CML-CMR (P = 0.0214). Our observations indicate that some lymphocyte subsets may be affected by imatinib therapy, even in CMR. The differences in subset cell fractions between CML-CMR and STOP-IM patients therefore may have some bearing on discontinuation of imatinib therapy. We were able to determine NK cell activity in 11 STOP-IM patients. This activity ranged from 24% to 69% (normal range, 18%–40%); 7 of the 11 patients had elevated NK cell activity, and a positive correlation was found between NK cell activity and NK cell percentages in the 11 STOP-IM patients.

Discussion:
We noticed deviation in some fractions of circulating lymphocytes in STOP-IM patients with CML, in comparison with CML patients who were CMR but were still taking imatinib. in STOP-IM patients in our study, an elevated cell fraction was detected only in CD3−CD56+ NK cells, and others were down-regulated. We were able to determine NK cell activity in 11 STOP-IM patients. This activity ranged from 24% to 69% (normal range, 18%–40%); 7 of the 11 patients had elevated NK cell activity, and a positive correlation was found between NK cell activity and NK cell percentages in the 11 STOP-IM patients. Two CMR patients satisfied criteria for both down-regulated CD3+CD8+CD62L+ cells and up-regulated CD3―CD56+ NK cells compared with those of healthy subjects.

Conclusion:
Our results therefore may aid in the selection of possible candidates for discontinuation of imatinib therapy in patients in CMR. The minimal requirements for discontinuation of imatinib treatment might be CMR duration of more than 2 years and low/intermediate Sokal scores at the time of CML diagnosis. In addition, increasing number of NK cells and decreased CD3+CD8+CD62L+ cell fractions may also be indications that imatinib therapy can be stopped.

Disclosures:
No relevant conflicts of interest to declare.