The Clinical Features and Survival Outcome of 107 Newly Diagnosed Advanced Stage Extranodal NK/T-Cell Lymphoma Cases: A Triple-Center Study

Figures & data

Table 1 Patient Characteristics

Characteristics	Patient Number (%)	CHOP Group (n = 28)	L-asp Group (n = 66)			P value (L-asp vs CHOP Group)
			Total	GELOXD (n = 44)	SMILE (n = 22)
Gender						0.4237
Male	75 (70.1)	21	44	28	16
Female	32 (29.9)	7	22	16	6
Age (years)						0.9702
> 60	20 (18.7)	5	12	7	0 5
≤ 60	87 (81.3)	23	54	37	0 17
Median (years)	42.0	37.5	41.5
ECOG PS						0.5275
0–1	105 (98.1)	27	65	43	0 22
2–4	2 (1.9)	1	1	1	0
B symptom						0.2049
Yes	61 (57.0)	13	40	25	0 15
No	46 (43.0)	15	26	19	0 7
IPI score	91	23	60	41	0 19	0.1642
> 1	31 (34.1)	16	50	36	0 14
≤ 1	60 (65.9)	7	10	5	0 5
LDH level	91	23	60	40	0 20	0.3745
Elevated	44 (48.4)	9	30	17	0 13
Normal	47 (51.6)	14	30	23	0 7
Primary sites						0.5596
UAT	88 (82.2)	23	52	36	0 17
NAT	19 (17.8)	4	13	8	0 5
Skin	9	2	5	3	0 2
Intestinal tract	6 (1.4)	1	5	3	0 2
Breast	1	0	1	1	0 0
Distant lymph nodes	3	1	2	1	0 1
PINK	107	28	66			0.2282
1–2	38 (35.5)	7	25	13	0 12
≥3	69 (64.5)	21	41	31	0 10
Immunophenotype
Ki- 67 ≥ 60%	62 (57.9)	18	32	22	0 10	0.1603
EBER +	101 (94.4)	25	62	41	0 21	0.4319

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; IPI, International Prognostic Index; LDH, lactate dehydrogenase; PINK, Prognostic Index of Natural Killer Lymphoma; EBER, EBV encoded RNA.

Table 2 The Response Rates for Different Treatment Regimens

	CHOP (n=28)	L-asp Containing Regimen (n=66)	VIPD (n=7)	P value (L-asp vs CHOP)	P value (VIPD vs CHOP)
CR	6	31	3	0.0204	0.2460
PR	6	14	2
SD	4	9	1
PD	12	12	1
ORR	42.9%	68.2%	71.4%	0.0215	0.2285

Figure 1 Kaplan-Meier survival curve of advanced stage ENKTL patients.

Notes: (A and B) The progression-free survival (PFS) (A) and overall survival (OS) (B) of all patients. (C) The progression-free survival in the CHOP and L-asp groups. (D) The overall survival in the CHOP and L-asp groups. (E) The progression-free survival in the SMILE and GELOXD groups. (F) The overall survival in the SMILE and GELOXD groups.

Figure 2 Significant impact of primary involved site, IPI score and PINK score on the survival outcome.

Notes: (A) The progression-free survival in the UAT and NUAT groups. (B) The overall survival in the UAT and NUAT groups. (C) The progression-free survival in the low-IPI and high-IPI groups. (D) The overall survival in the low-IPI and high-IPI groups. (E) The progression-free survival in the low-PINK and high-PINK groups. (F) The overall survival in the low-PINK and high-PINK groups.

Table 3 Univariate and Multivariate Analysis of Prognostic Factors for Survivals (by Cox Regression)

Clinical Factor	Progression-Free Survival				Overall Survival
	Univariate		Multivariate		Univariate		Multivariate
	P	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)
Aged ≥ 60y	0.011	0470 (0.255–0.865)			0.019	0.491 (0.264–0.909)
Gender	0.817	0.921 (0.458–1.852)			0.820	0.919 (0.444–1.903)
B symptom	0.928	1.029 (0.550–1.924)			0.909	0.963 (0.502–1.847)
LDH	0.532	1.243 (0.628–2.462)			0.649	1.173 (0.648–2.156)
Ki67≥60%	0.238	0.605(0.262–1.395)			0.553	0.763(0.313–1.862)
Primary tumor site (UAT vs NUAT)	0.002	0.377(0.195–0.728)			0.012	0.435(0.221–0.855)
Stage (III vs IV)	0.147	1.837 (0.807–4.180)			0.238	1.648(0.719–3.778)
IPI score ≥ 2	0.029	0.370 (0.144–0.951)			0.039	0.389 (0.151–0.999)
PINK score≥3	0.001	0.417 (0.239–0.726)	0.014	0.335 (0.141–0.798)	0.011	0.491 (0.279–0.866)	0.048	0.415 (0.174–0.991)
β2 -microglobulin elevated > 2.5mg/L	0.974	0.986 (0.416–2.333)			0.770	0.874 (0.355–2.154)
Hemoglobin < 110g/L	0.568	0.828 (0.420–1.632)			0.289	0.677 (0.329–1.391)
Leukopenia < 4×10^9/L	0.415	1.359(0.650–2.842)			0.732	1.140 (0.538–2.419)
Platelet < 150×10^9/L	0.649	0.853 (0.431–1.690)			0.367	0.723 (0.358–1.461)
L-asp containing regimen	0.106	1.548(0.899–2.667)			0.042	1.776(1.022–3.089)
CR after treatment	0.000	5.409 (2.893–10.113)	0.002	4.577 (1.72412.150)	0.000	5.150 (2.717–9.759)	0.045	2.507 (1.021–6.153)

Table 4 Grade 3/4 Toxicity That Occurred in the Two Groups

Toxicity	GELOXD (n=44)	SMILE (n=22)	P value
Hematologic	7	13	0.0003
Neutropenia	6(13.6%)	12(54.5%)
Anemia	4(9.1%)	8(36.4%)
Thrombocytopenia	2(4.5%)	9(40.9%)
Febrile neutropenia	1(2.3%)	2(9.1%)
Non-hematologic	8	14	0.0002
Nausea	5 (11.4%)	8 (36.4%)
Vomiting	2 (4.5%)	3 (13.6%)
Diarrhea	0	2 (9.1%)
Transaminase elevation	2 (4.5%)	7 (31.8%)
ALT elevation	2 (4.5%)	3 (13.6%)
AST elevation	1 (2.3%)	5 (22.7%)
Hyperbilirubinemia	1 (2.3%)	3 (13.6%)
Peripheral neuropathy	1 (2.3%)	2 (9.1%)
Fatigue	1 (2.3%)	3 (13.6%)