Objective: To compare the differences of deep molecular response (DMR) rate and time of obtaining DMR between dasatinib treated patients with increased and normal levels of large granular lymphocytes (LGLs) in newly diagnosed or imatinib resistant/intolerant chronic myeloid leukemia (CML) patients with positive BCR-ABL fusion gene. Methods: LGLs in peripheral blood were counted by flow cytometry and BCR-ABL fusion gene transcriptional level was detected by real-time quantitative polymerase chain reaction in 25 CML patients before and 1, 3, 6, 9, 12, 15, 18 months after dasatinib treatment. The enrolled patients were classified into LGLs+ group and LGLs- group according to whether the LGL counts were increased or not. Results: Among the 25 patients investigated, LGLs in 15 cases (5/15, 60%) were increased. Five cases in LGL+ group obtained DMR (33.3%) which was significantly higher than that of LGL- group (33.3% vs 10 %, P < 0.05). The median time of obtaining DMR in LGLs+ group and LGLs- group were 12 and 15 months respectively. Conclusions: Increased LGLs can be used as an indicator of prognosis in CML patients with positive BCR-ABL fusion gene who treated with dasatinib.
Chronic Myeloid Leukemia, Large Granular Lymphocyte, Dasatinib, Deep Molecular Response
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Chronic Myelogenous Leukemia，V.2.2008. NCCN Web Site. 8-28-2007. Accessed October 25, 2007.
- Zhang A，Hu Q，Zhang L, et al. Clinical analysis of children diagnosed with BCR/ABL positive acute lymphoblastic leukemia. Leukemia. Lymphoma 2014, 23 (3):160-162.
- Zhou B，An C, Pu X. Research and development status of next generation tyrosine kinase inhibitor agents. Chinese Journal of New Drugs 2011, 20(7):1661-1666
- Mustjoki S, Ekblom M, Arstila, TP, et al. Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy. Leukemia 2009, 23:1398-1405.
- Kim DH, Kamel-Reid S, Chang H, et al. Natural killer or Natural killer/T cell lineage large granular lymphocytes associated with dasatinib therapy for Philadelphia chromosome positive leukemia. Haematologica 2009, 94: 135-139.
- Nagata Y, Ohashi K, Fukuda S, et al. Clinical features of dasatinib-induced large granular lymphocytosis and pleural effusion. Int J Hematol 2010, 91:799–807.
- Powers JJ, Dubovsky JA, Epling-Burnette PK, et al. A molecular and functional analysis of large granular lymphocyte expansions in patients with chronic myelogenous leukemia treated with tyrosine kinase inhibitors. Leuk Lymphoma 2015, 2:668–679.
- Tanaka H and Nakashima S. Rapid and sustained increase of large granular lymphocytes and rare cytomegalovirus reactivation during dasatinib treatment in chronic myelogenous leukemia patients. Int J Hematol 2012, 96:308–319.
- Paydas S. Dasatinib, large granular lymphocytosis, and pleural effusion: Useful or adverse effect? Crit Rev Oncol Hematol 2014, 89:242–247.
- Kumagai T, Matsuki E, Inokuchi K, et al. Relative increase in lymphocytes from as early as 1 month predicts improved response to dasatinib in chronic-phase chronic myelogenous leukemia. Int J Hematol 2014, 99:41–52.
- Inokuchi K, Kumagai T, Matsuki E, et al. Efficacy of molecular response at 1 or 3 months after the initiation of dasatinib treatment can predict an improved response to dasatinib in imatinib-resistant or imatinib-intolerant Japanese patients with chronic myelogenous leukemia during the chronic phase. J Clin Exp Hematol 2014, 54:197–204.
- Lee SJ, Jung CW, Kim DY, et al. Retrospective multicenter study on the development of peripheral lymphocytosis following second-line dasatinib therapy for chronic myeloid leuk-mia. Am J Hematol 2011, 86:346–350.
- Iriyama N, Fujisawa S, Yoshida C, et al. Early cytotoxic lymphocyte expansion contributes to a deep molecular response to dasatinib in patients with newly diagnosed chronic myeloid leukemia in the chronic phase: results of the D-first study. Am J Hematol 2015, 90:819-824.
- Falchi L, Kantarjian HM, Wang X, et al. Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors. Am J Hematol 2013, 88 (12):1024-1029.
- Savona MR and Saglio G. Identifying the time to change BCR-ABL inhibitor therapy in patients with chronic myeloid leukemia. Acta Haematol 2013, 130 (4):268-278.
- Shan NP, Tran C, Lee FY et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004, 305 (5682): 399-401.
- Guo F, Chen Y, Yang M et al. Therapeutic effect of dasatinib on chronic myelogenous leukemia patients in acceleration stage. Chinese Journal of Disease Control 2015, 19(6):601-604.
- Qing H，Shi H，Liu Z et al. Peripheral blood T lymphocyte subgroup detection and clinical significance in 253 patients diagnosed with malignant tumor. Laboratory Diagnostics of China 2009, 13(11):1589-1590.
- Wu X, Zhang Q, Hou S et al. Detection and clinical significance of peripheral blood T lymphocyte subgroup and natural killer cell activity on refractory lymphoma patients. Leukemia. Lymphoma 2011, 20(3):162-164.
- Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol 2010, 28:445-489.
- Yao Z, Zhao G, Wang, Y, et al. Analysis of the relationship between clinical status and quantitative of BCR/ABL in CML patients. Chinese Journal of Experimental Hematology 2009, 17(4):861-865.
- Qiu Z, Xu W, Li J. Large granular lymphocytosis during dasatinib therapy. Cancer Biology &Therapy 2014, 15: 247-255.
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