Prognostic significance of peripheral blood absolute lymphocyte count and derived neutrophil to lymphocyte ratio in patients with newly diagnosed extranodal natural killer/T-cell lymphoma

Figures & data

Table 1 Correlation between dNLR and clinical characteristics of ENKTL patients

	Total (%)	dNLR		ALC
Mean ± SD	P-value	Mean ± SD	P-value
	33
Gender			0.129		0.602
Male	26 (78.8%)	2.658±1.804		1.264±0.616
Female	7 (21.2%)	1.570±0.584		1.109±0.690
Age (year)			0.588		0.664
<60	27 (81.8%)	2.503±1.787		1.208±0.602
≥60	6 (18.2%)	2.084±1.095		1.333±0.774
Ann Arbor Stage			0.047		0.188
I/II	13 (39.4%)	1.801±0.832		1.410±0.539
III/IV	20 (60.6%)	2.834±1.962		1.115±0.661
B symptoms			0.194		0.941
Absence	13 (39.4%)	2.018±0.807		1.221±0.523
Presence	20 (60.6%)	2.693±2.033		1.238±0.693
ECOG PS score			0.050		0.002
0 or 1	26 (78.8%)	1.942±0.925		1.381±0.550
≥2	7 (21.2%)	4.612±2.556		0.555±0.501
Serum LDH			0.026		0.01
Normal	18 (54.5%)	2.235±1.272		1.478±0.476
Increased<3×NL	9 (27.3%)	1.763±1.243		1.130±0.461
Increased≥3×NL	6 (18.3%)	3.999±2.474		0.642±0.854
Extranodal site			0.458		0.231
0 or 1	21 (63.6%)	2.233±1.285		1.331±0.584
≥2	12 (36.4%)	2.768±2.230		1.057±0.679
Distant lympho node			0.013		0.026
Not involved	13 (39.4%)	1.651±0.745		1.525±0.460
Involved	20 (60.6%)	2.932±1.919		1.040±0.652
BM involvement			0.715		0.085
Absence	31 (93.9%)	2.348±1.551		1.278±0.612
Presence	2 (6.1%)	3.648±3.824		0.495±0.318
β2-microglobulin			0.035		0.029
<2.8 mg/L	19 (58%)	1.825±0.775		1.451±0.429
≥2.8 mg/L	14 (42%)	3.245±2.198		0.933±0.734
Blood EBV DNA			0.126		0.011
<5,000 copies/mL	19 (57.6%)	1.991±0.942		1.462±0.527
≥5,000 copies/mL	14 (42.4%)	3.019±2.243		0.917±0.625
Treatment			0.879		0.504
RT alone	11 (33.3%)	2.418±1.877		1.394±0.522
CT alone	17 (51.5%)	2.533±1.786		1.109±0.678
Combined RT and CT	5 (15.2%)	2.087±0.849		1.286±0.678
Response			0.123		0.349
No response (SD, PD)	18 (54.5%)	2.819±2.075		1.141±0.752
Response (CR, PR)	15 (45.5%)	1.957±0.871		1.339±0.425
PINK score			0.236		0.125
0 or 1	17 (51.5%)	2.088±1.338		1.394±0.524
≥2	16 (48.5%)	2.788±1.953		1.058±0.690
IPI Score			0.044		0.024
0 or 1	17 (51.5%)	1.837±0.787		1.465±0.571
≥2	16 (48.5%)	3.055±2.126		0.923±0.597

Note: Bold signifies P<0.05.

Abbreviations: ALC, absolute lymphocyte count; dNLR, derived neutrophil to lymphocyte ratio; ECOG PS, Eastern Cooperative Oncology Group performance status; ENKTL, extranodal natural killer/T-cell lymphoma; LDH, lactate dehydrogenase; BM, bone marrow; EBV, Epstein–Barr virus; RT, radiotherapy; CT, chemotherapy; CR, complete remission; PR, partial remission; SD, stable disease; PD, progressive disease; PINK, prognostic index for NK/T cell lymphoma; IPI, international prognostic index; ULN, upper limit of normal.

Figure 1 ROC curves for dNLR (A) and ALC (B) at diagnosis.

Abbreviations: ALC, absolute lymphocyte count; AUC, area under the curve; dNLR, derived neutrophil to lymphocyte ratio; ROC, receiver operating characteristic.

Table 2 Association between clinical variables and dNLR, ALC

Variables	Total (n=33)	dNLR≥3.6 (n=5)	dNLR<3.6 (n=28)	P-value	ALC≥0.8×10^9/L (n=24)	ALC<0.8×10^9/L n=9	P-value
Gender				0.559			0.358
Male	26	5 (100.0%)	21 (75.0%)		20 (83.3%)	6 (66.7%)
Female	7	0 (0.0%)	7 (25.0%)		4 (16.7%)	3 (33.3%)
Age (year)				1			1
<60	27	4 (80.0%)	23 (82.1%)		20 (83.3%)	7 (77.8%)
≥60	6	1 (20.0%)	5 (17.9%)		4 (16.7%)	2 (22.2%)
Ann Arbor Stage				0.131			0.263
I/II	13	0 (0.0%)	13 (46.4%)		11 (45.8%)	2 (22.2%)
III/IV	20	5 (100.0%)	15 (53.6%)		13 (54.2%)	7 (77.8%)
B symptoms				0.131			1
Absence	13	0 (0.0%)	13 (46.4%)		10 (41.7%)	3 (33.3%)
Presence	20	5 (100.0%)	15 (53.6%)		14 (58.3%)	6 (66.7%)
ECOG PS score				0.004			0.009
0 or 1	26	1 (20.0%)	25 (89.3%)		22 (91.7%)	4 (44.4%)
≥2	7	4 (80.0%)	3 (10.7%)		2 (8.3%)	5 (55.6%)
Serum LDH				<0.001			0.001
Normal	18	1 (20.0%)	17 (60.7%)		17 (70.8%)	1 (11.1%)
Increased<3×ULN	9	0 (0.0%)	9 (32.1%)		6 (25.0%)	3 (33.3%)
Increased≥3×ULN	6	4 (80.0%)	2 (7.2%)		1 (4.2%)	5 (55.6%)
Distant lympho node				0.131			0.047
Not involved	13	0 (0.0%)	13 (46.4%)		13 (54.2%)	1 (11.1%)
Involved	20	5 (100.0%)	15 (53.6%)		11 (45.8%)	8 (88.9%)
BM involvement				0.284			0.068
Absence	31	4 (80.0%)	27 (96.4%)		24 (100.0%)	7 (77.8%)
Presence	2	1 (20.0%)	1 (3.6%)		0 (0.0%)	2 (22.2%)
β2-microglobulin				0.008			0.02
<2.8 mg/L	19	0 (0.0%)	19 (67.9%)		18 (75.0%)	1 (11.1%)
≥2.8 mg/L	14	5 (100.0%)	9 (32.1%)		6 (25.0%)	8 (88.9%)
Blood EBV DNA				0.628			0.019
<5,000 copies/mL	19	2 (40.0%)	17 (60.7%)		17 (70.8%)	2 (22.2%)
≥5,000 copies/mL	14	3 (60.0%)	11 (39.3%)		7 (29.2%)	7 (77.8%)
Treatment				0.344			0.163
RT alone	11	1 (20.0%)	10 (35.7%)		10 (41.7%)	1 (11.1%)
CT alone	17	4 (80.0%)	13 (46.4%)		10 (41.7%)	7 (77.8%)
Combined RT and CT	5	0 (0.00%)	5 (17.9%)		4 (16.7)	1 (11.1%)
Response				0.049			0.021
No response (SD, PD)	18	5 (100.0%)	13 (46.4%)		10 (41.7%)	8 (88.9%)
Response (CR, PR)	15	0 (0.0%)	15 (53.6%)		14 (58.3%)	1 (11.1%)
PINK				0.175			0.269
0 or 1	17	1 (20.0%)	16 (57.1%)		14 (58.3%)	3 (33.3%)
≥2	16	4 (80.0%)	12 (42.9%)		10 (41.7%)	6 (66.7%)
IPI Score				0.018			0.057
0 or 1	17	0 (0.0%)	17 (60.7%)		15 (62.5%)	2 (22.2%)
≥2	16	5 (100.0%)	11 (39.3%)		9 (37.5%)	7 (77.8%)

Note: Bold signifies P<0.05.

Abbreviations: ALC, absolute lymphocyte count; dNLR, derived neutrophil to lymphocyte ratio; ALC, absolute lymphocyte count; ECOG PS, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; BM, bone marrow; EBV, epstein-barr virus; RT, radiotherapy; CT, chemotherapy; CR, complete remission; PR, partial remission; SD, stable disease; PD, progressive disease; PINK, prognostic index for NK/T cell lymphoma; IPI, international prognostic index; ULN, upper limit of normal.

Figure 2 Kaplan–Meier curve of overall survival according to dNLR (A) and ALC (B) at diagnosis in patients with ENKTL.

Abbreviations: ALC, absolute lymphocyte count; AUC, area under the curve; dNLR, derived neutrophil to lymphocyte ratio; ENKTL, extranodal natural killer/T-cell lymphoma.

Figure 3 Kaplan–Meier curve of progression-free survival according to dNLR (A) and ALC (B) at diagnosis in patients with ENKTL.

Abbreviations: ALC, absolute lymphocyte count; AUC, area under the curve; dNLR, derived neutrophil to lymphocyte ratio; ENKTL, extranodal natural killer/T-cell lymphoma.

Figure 4 Kaplan–Meier curve of overall survival and progression-free survival according to dNLR (A and B) and ALC (C and D) at diagnosis in ENKTL patients with stage III/IV disease.

Abbreviations: ALC, absolute lymphocyte count; AUC, area under the curve; dNLR, derived neutrophil to lymphocyte ratio; ENKTL, extranodal natural killer/T-cell lymphoma.

Table 3 Univariate and multivariate Cox regression analysis of overall survival in patients with ENKTL

Prognostic factors	Overall survival
	Univariate analysis		Multivariate analysis
HR (95% CI)	P-value	HR (95% CI)	P-value
Male sex	0.342 (0.095–1.227)	0.1	n.d.	n.d.
Age≥60 years	0.463 (0.059–3.659)	0.465	n.d.	n.d.
Stage III/IV	7.378 (0.949–57.353)	0.056	9.202 (0.567–149.365)	0.119
B symptoms	1.285 (0.381–4.328)	0.686	n.d.	n.d.
ECOG PS score ≥2	4.865 (1.477–16.030)	0.009	2.520 (0.183–34.801)	0.490
Serum LDH > normal	3.373 (0.979–11.614)	0.054	1.674 (0.329–8.510)	0.535
Distant lympho node involved	3.237 (0.705–14.857)	0.131	n.d.	n.d.
BM involvement	3.267 (0.691–15.454)	0.135	n.d.	n.d.
β2-MG ≥2.8mg/L	4.795 (1.223–18.809)	0.025	0.556 (0.030–10.246)	0.693
Blood EBV DNA ≥5,000 copies/mL	2.714 (0.814–9.054)	0.104	n.d.	n.d.
No response to treatment	61.243 (0.573–6,543.069)	0.084	n.d.	n.d.
PINK score ≥2	2.356 (0.704–7.891)	0.165	n.d.	n.d.
IPI Score ≥2	6.332 (1.379–29.074)	0.018	1.358 (0.142–12.955)	0.790
ALC<0.8×10^9/L	11.251 (2.946–42.968)	0.0004	36.023 (2.438–532.243)	0.009
dNLR ≥3.6	5.938 (1.790–19.704)	0.004	0.103 (0.05–2.098)	0.140

Note: Bold signifies P<0.05.

Abbreviations: ALC, absolute lymphocyte count; dNLR, derived neutrophil to lymphocyte ratio; ECOG PS, Eastern Cooperative Oncology Group performance status; ENKTL, extranodal natural killer/T-cell lymphoma; LDH, lactate dehydrogenase; BM, bone marrow; β2-MG, β2-microglobulin; EBV, Epstein–Barr virus; PINK, prognostic index for NK/T cell lymphoma; IPI, international Prognostic Index; ULN, upper limit of normal. n.d.: not done in multivariate analysis.

Table 4 Univariate and multivariate Cox regression analysis of progression-free survival in patients with ENKTL

Prognostic Factors	Progression-free survival
	Univariate analysis		Multivariate analysis
HR (95% CI)	P-value	HR (95% CI)	P-value
Male sex	0.371 (0.107–1.281)	0.117	n.d.	n.d.
Age≥60 years	1.664 (0.439–6.312)	0.454	n.d.	n.d.
Stage III/IV	1.807 (0.486–6.727)	0.378	n.d.	n.d.
B symptoms	1.351 (0.402–4.539)	0.626	n.d.	n.d.
ECOG PS score ≥2	2.568 (0.809–8.147)	0.109	n.d.	n.d.
Serum LDH > normal	3.733 (1.111–12.541)	0.033	2.063 (0.534–7.968)	0.294
Distant lympho node Involved	4.412 (0.963–20.206)	0.056	n.d.	n.d.
BM involvement	2.799 (0.598–13.098)	0.191	n.d.	n.d.
β2-MG ≥2.8 mg/L	3.350 (0.972–11.541)	0.055	n.d.	n.d.
Blood EBV DNA≥5,000 copies/mL	3.588 (0.968–13.295)	0.056	n.d.	n.d.
No response to treatment	68.634 (0.655–7,191.306)	0.075	n.d.	n.d.
PINK score ≥2	1.405 (0.442–4.471)	0.564	n.d.	n.d.
IPI Score ≥2	3.426 (0.923–12.717)	0.066	n.d.	n.d.
ALC <0.8×10^9/L	7.392 (2.213–24.693)	0.001	7.698 (1.573–37.679)	0.012
dNLR ≥3.6	4.199 (1.326–13.297)	0.015	0.615 (0.131–2.894)	0.539

Note: Bold signifies P<0.05.

Abbreviations: ALC, absolute lymphocyte count; dNLR, derived neutrophil to lymphocyte ratio; ECOG PS, Eastern Cooperative Oncology Group performance status; ENKTL, extranodal natural killer/T-cell lymphoma; LDH, lactate dehydrogenase; BM, bone marrow; β2-MG, β2-microglobulin; EBV, epstein-barr virus; PINK, prognostic index for NK/T cell lymphoma; IPI, international prognostic index; ULN, upper limit of normal. n.d.: not done in multivariate analysis.