Large granular lymphocytosis during dasatinib therapy

Figures & data

Table 1. Summary of articles about LGL lymphocytosis during daatinib therapy

Reference	No. of patients	Median age (years)	Dasatinib dose (mg/d)	Rate of LGL lymphocytosis	Lymphocyte counts (10^9/L)	Median interval from starting dasatinib to LGL	Median number of LGL (10^9/L)
Mustjoki et al.^15	30	54 (25–76)	140	73% (22)	4–20	3 mo (range 1–15 mo)	NR
Kreutzman et al.^16	20	51 (29–78)	NR	50% (10)	NR	NR	NR (range 4–20)
Nagata et al.^17	20	50 (29–81)	100–180	45% (9)	NR	1 mo (range 1–8 mo)	6.5 (range 2.9–17.4)
Kim et al.^18	18	NR	140	44% (8)	4.6–8.8	4 mo (range 1.5–15 mo)	NR (range 2.2–5.6)
Tanaka et al.^19	25	64 (20–84)	50–140	60% (12)	NR	11 wk (range 6–44 wk)	3.0 (range 1.6–6.0)
Valent et al.^20	15	NR	100–140	27% (4)	5.0–6.9	NR	NR (range 2.3–4.83)
Lee et al.^21^,*	50	49	100–140	46% (23)	3.7–7.9	4 mo (range 1–13 mo)	NR
Powers et al.^22	16	56 (48–65)	NR	31% (5)	NR	NR	1.6 (range 0.6–2.7)

Note: *In this study, the development of lymphocytosis could not be directly interpreted as an expansion of large granular lymphocytes because a PB smear was not available; NR, not reported.

Table 2. The relationship between favorable response and LGL lymphocytosis

Reference	MMR			CMR
	LGL^+	LGL^−	P	LGL^+	LGL^−	P
Mustjoki et al.^15	17/22 (77%)	2/8 (25%)	0.015	12/22 (55%)	1/8 (13%)	0.047
Nagata et al.^17	8/9 (89%)	6/11 (55%)	0.08	NR
Kim et al.^18	8/8 (100%)	3/10 (30%)	0.01	7/8	2/10	0.003
Tanaka et al.^19	NR			4/5 (80%)	0/3 (0%)	0.01
Lee et al.^21	12/23 (52%)	5/27 (15%)	0.05	10/23 (44%)	4/27 (15%)	0.024
Mustjoki et al.^29	7/7 (100%)	1/30 (3%)	<0.00	6/7 (86%)	1/30 (3%)	<0.00

MMR, major molecular response; CMR, complete molecular response; NR, not reported.

Table 3. The relationship between PE and LGL lymphocytosis

Reference	PE
	LGL^+	LGL^−
Mustjoki et al.^15	13/22 (59%)	NR
Nagata et al.^17	5/9 (56%)	3/11 (27%)
Tanaka et al.^19	9/15 (60%)	2/10 (20%)
Lee et al.^21	5/23 (22%)	6/27 (22%)
Powers et al.^22	3/5 (60%)	2/11 (18%)

PE, pleural effusions; NR, not reported.

Figure 1. The pathogenesis of LGL lymphocytosis during dasatinib therapy.

Mustjoki S, Ekblom M, Arstila TP, Dybedal I, Epling-Burnette PK, Guilhot F, Hjorth-Hansen H, Höglund M, Kovanen P, Laurinolli T, et al. Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy. Leukemia 2009; 23:1398 - 405; http://dx.doi.org/10.1038/leu.2009.46; PMID: 19295545

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Kreutzman A, Juvonen V, Kairisto V, Ekblom M, Stenke L, Seggewiss R, Porkka K, Mustjoki S. Mono/oligoclonal T and NK cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy. Blood 2010; 116:772 - 82; http://dx.doi.org/10.1182/blood-2009-12-256800; PMID: 20413659

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Nagata Y, Ohashi K, Fukuda S, Kamata N, Akiyama H, Sakamaki H. Clinical features of dasatinib-induced large granular lymphocytosis and pleural effusion. Int J Hematol 2010; 91:799 - 807; http://dx.doi.org/10.1007/s12185-010-0565-1; PMID: 20405252

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Kim DH, Kamel-Reid S, Chang H, Sutherland R, Jung CW, Kim HJ, Lee JJ, Lipton JH. Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia. Haematologica 2009; 94:135 - 9; http://dx.doi.org/10.3324/haematol.13151; PMID: 19066329

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Tanaka H, Nakashima S, Usuda M. 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 - 19; http://dx.doi.org/10.1007/s12185-012-1132-8; PMID: 22767140

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Valent JN, Schiffer CA. Prevalence of large granular lymphocytosis in patients with chronic myelogenous leukemia (CML) treated with dasatinib. Leuk Res 2011; 35:e1 - 3; http://dx.doi.org/10.1016/j.leukres.2010.08.022; PMID: 20888043

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Lee SJ, Jung CW, Kim DY, Lee KH, Sohn SK, Kwak JY, Kim HJ, Kim IH, Park S, Kim DH. Retrospective multicenter study on the development of peripheral lymphocytosis following second-line dasatinib therapy for chronic myeloid leukemia. Am J Hematol 2011; 86:346 - 50; http://dx.doi.org/10.1002/ajh.21980; PMID: 21442637

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Powers JJ, Dubovsky JA, Epling-Burnette PK, Moscinski L, Zhang L, Mustjoki S, Sotomayor EM, Pinilla-Ibarz JA. A molecular and functional analysis of large granular lymphocyte expansions in patients with chronic myelogenous leukemia treated with tyrosine kinase inhibitors. Leuk Lymphoma 2011; 52:668 - 79; http://dx.doi.org/10.3109/10428194.2010.550074; PMID: 21271862

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Mustjoki S, Auvinen K, Kreutzman A, Rousselot P, Hernesniemi S, Melo T, Lahesmaa-Korpinen AM, Hautaniemi S, Bouchet S, Molimard M, et al. Rapid mobilization of cytotoxic lymphocytes induced by dasatinib therapy. Leukemia 2013; 27:914 - 24; http://dx.doi.org/10.1038/leu.2012.348; PMID: 23192016

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