Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment-free remission
| Autor: | Tadashi Murase, Kaichi Nishiwaki, Hisashi Sakamaki, Naoki Takezako, Kosei Matsue, Junichi Sakamoto, Chiaki Nakaseko, Satoshi Morita, Kazuteru Ohashi, Yasuji Kouzai, Hina Takano, Takashi Kumagai, Hisashi Wakita, Shimousa Hematology Study Groups Kanto Cml, Chikashi Yoshida, Koiti Inokuchi |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cancer Research Lymphocyte Dasatinib Basal (phylogenetics) 0302 clinical medicine Cytotoxic T cell Prospective Studies CML Aged 80 and over education.field_of_study biology Remission Induction General Medicine Middle Aged TKI Killer Cells Natural medicine.anatomical_structure Treatment Outcome Oncology 030220 oncology & carcinogenesis Female Original Article medicine.drug Adult medicine.medical_specialty NK stop T cell CD3 Population 03 medical and health sciences Clinical Research Internal medicine Leukemia Myelogenous Chronic BCR-ABL Positive medicine Humans Lymphocyte Count education Protein Kinase Inhibitors Aged business.industry Original Articles 030104 developmental biology Endocrinology biology.protein business CD8 Follow-Up Studies T-Lymphocytes Cytotoxic |
| Zdroj: | Cancer Science |
| ISSN: | 1349-7006 |
| Popis: | This study presents the final report of the multicenter, prospective tyrosine kinase inhibitor discontinuation study, D‐STOP, after a 3‐year follow‐up of 54 patients with chronic CML who discontinued dasatinib after a sustained deep molecular response (DMR) for ≥2 years with dasatinib treatment. Estimated treatment‐free remission (TFR) rates at 12 and 36 months were 63.0% [95% confidence interval (CI): 48.7‐74.3] and 59.3% (95% CI: 45.0‐71.0), respectively. CD3−CD56+ NK, CD16+CD56+ NK, and CD57+CD56+ NK large granular lymphocyte (NK‐LGL), CD8+CD4– cytotoxic T cell, and CD57+CD3+ T‐LGL cell numbers were relatively elevated throughout the 24‐month consolidation only in failed patients who molecularly relapsed within 12 months. In successful patients, these subsets elevated transiently after 12 months, but returned to basal levels after 24‐month consolidation. Therefore, smaller changes in NK/T, particularly the NK subset throughout consolidation, reflected higher TFR rates. TFR rates of those patients exhibiting elevation in CD3−CD56+ NK >376 cells/μL, CD16+CD56+ NK > 241 cells/μL, or CD57+CD56+ NK‐LGL >242 cells/μL during consolidation compared with others were 26.7% (8.3%‐49.6%) vs 78.3% (55.4%‐90.3%), HR 0.032 (0.0027‐0.38; P = .0064), 31.2% (11.4%‐53.6%) vs 85.0% (60.4%‐94.9%), HR 0.039 (0.0031‐0.48; P = .011), or 36.8% (16.5%‐57.5%) vs 77.3% (53.7%‐89.8%), HR 0.21 (0.065‐0.69; P = .010), respectively. Therefore, silent responses of T/NK subsets to dasatinib throughout consolidation were significant for longer TFR. Elevated NK/T, particularly NK lymphocytes responsive to dasatinib, may be immunologically insufficient to maintain TFR. Their decline, subsequently replaced by altered lymphocyte population with less response to dasatinib during sustained DMR, might be immunologically significant. (D‐STOP, NCT01627132). The figure shows that silent NK/T cell reactions against dasatinib, particularly that of NK cells, during sustained DMR before dasatinib discontinuation are significant for longer treatment‐free remission. |
| Databáze: | OpenAIRE |
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