Impact of Serum Levels of IL-18 and Soluble IL-2 Receptor on the Clinical Outcome of Patients With Diffuse Large B-cell Lymphoma Treated with R-CHOP Regimen

Figures & data

Table 1. Patients characteristics.

Variable	Frequency (n = 73)	Percentage
Gender – Males – Females	44 29	60% 40%
Median age (years) (Range)	53 (18xx68)	–
ECOG PS – PS 0 – PS 1 – PS 2 – PS 3	26 32 10 5	36% 44% 14% 6%
LDH level – Normal – Elevated	31 42	42.5% 57.5%
Number of extranodal sites – 0 – 1 – 2 or more	44 24 5	60% 33% 7%
Extranodal sites – Stomach – Bone marrow – Liver – Chest wall – Muscle – Pancreas – Paraspinal – Bone – Breast – Paratoid – Kidney – Lung – Small intestine	9 6 5 3 2 2 2 1 1 1 1 1 1	-
Stage I Stage II Stage III Stage IV	10 27 17 19	14% 37% 23% 26%
IPI risk score – Low – Low intermediate – High intermediate – High	34 21 12 6	47% 29% 16% 8%
B symptoms – Absent – Present	48 25	66% 34%
Bulky disease (≥7.5 cm) – Absent – Present	60 13	82% 18%
HBsAg −ve +ve HBcAB −ve +ve HBV DNA Not detectable Detectable	72 1 73 0 1 0	98% 2% 100% 0% 100% 0%
HCV Ab −ve +ve HCV RNA Not detectable Detectable	43 30 20 10	59% 41% 77% 33%

ECOG: Eastern Cooperative Oncology Group; IPI: International Prognostic Index; PS: Performance status.

Table 2. Serum IL-18 level according to conventional prognostic factors.

Factor		Serum IL-18			Serum sIL-2R
		Median	Range	p-value	Median	Range	p-value
All patients		10.8	3.8 – 231.7		468.8	67.5 – 2362.6
Gender	Males	10.8	3.8 – 231.7	0.739	456.8	67.5 – 2331.6	0.955
	Females	10.8	4.8 – 110.5		468.8	94.8 – 2362.6
Age	≤60	9.9	3.8 – 159	0.052	355.3	67.5 – 2362.6	<0.001
	>60	13.5	5.8 – 231.7		1145.7	98.7 – 2331.6
PS	0 or 1	10.6	3.8 – 231.7	0.465	454.7	67.5 – 2362.6	0.594
	2 – 4	11.0	5.6 – 86.5		468.8	104.3 – 2096.2
LDH	Normal	8.5	3.8 – 110.5	0.017	330	67.5 – 1942.2	<0.001
	Elevated	12.8	4.8 – 231.7		799.2	104.3 – 2362.6
Number of extranodal sites	0 or 1	10.9	3.8 – 231.7	0.243	422.7	67.5 – 2231.6	0.078
	≥2	9.3	5.6 – 28.5		766.4	478.8 – 2362.6
Clinical stage	I, II	9.0	3.8 – 110.5	0.066	350.0	67.5 – 1942.2	0.001
	III, IV	12.8	4.8 – 231.7		799.2	104.3 – 2362.6
IPI	L	8.9	3.8 – 110.5	0.615	310.9	67.5 – 1942.2	<0.001
	LI	12.1	5.8 – 159		725.6	104.3 – 1990.5
	HI	13.5	5.6 – 231.7		1819.6	541.8 – 2362.6
	H	22.2	9.3 – 79.1		1989.2	478.8 – 2080
B symptom	(−)	10.9	3.8 – 159	0.949	376.8	94.8 – 2231.6	0.036
	(+)	10.6	4.8 – 231.7		725.6	67.5 – 2362.6
Bulky sites	(−)	9.9	3.8 – 231.7	0.231	451.8	67.5 – 2362.6	0.171
	(+)	13.8	4.8 – 79.1		598.0	171.7 – 2231.6
HCV Ab	(−)	8.63	3.8 – 159	0.438	414.7	67.5 – 2080	0.069
	(+)	13.8	5.6 – 231.7		725.6	98.7 – 2362.6

Values in bold highlight variables with significant p value.

HCV Ab: Hepatitis C virus antibodies; IPI: International prognostic index; LDH: LDH level; PS: Performance status.

Table 3. Remission rate and survival outcome according to serum levels IL-18 and sIL-2R and other prognostic factors.

Factor		Number	CR rate		3-year DFS		3-year OS
			Percentage	p-value	Percentage	p-value	Percentage	p-value
Serum IL-18 (ROC)	≤11.3 pg/ml	39	79.5	0.339	49.3	0.279	62.9	0.153
	>11.3 pg/ml	34	69.7		66.2		72.1
Serum IL-18 (mean)	≤22.2 pg/ml	60	76.7	0.465	72.1	0.127	77.8	0.008
	>22.2 pg/ml	13	66.7		NR		55.4
Serum IL-18 (median)	≤10.8 pg/ml	37	78.4	0.496	40.9	0.126	54.8	0.280
	>10.8 pg/ml	36	71.4		70.1		73.7
Serum sIL-2R	≤592.4 U/ml	44	90.9	0.001	75.4	0.007	95.4	0.001
	>592.4 U/ml	29	50.0		35.4		NR
Gender	Males	44	79.5	0.264	53.4	0.131	68.1	0.854
	Females	29	67.9		93.3		86.1
Age	≤60	52	80.4	0.100	67.4	0.581	83.9	0.124
	>60	21	61.9		55.0		49.8
PS	0 or 1	58	78.9	0.132	65.0	0.385	72.7	0.116
	2–4	15	60		NR		71.8
LDH	Normal	31	87.1	0.039	69.8	0.975	100	0.014
	Elevated	42	65.9		36.0		59.0
Number of extranodal sites	0 or 1	68	77.9	^†	60.5	^†	74.3	0.038
	≥2	5	25.0		NR		NR
Clinical stage	I, II	37	86.5	0.021	81.5	0.008	82.6	0.012
	III, IV	36	62.9		NR		61.4
IPI	L	34	88.2	0.003	85.3	^†	97.0	0.001
	LI	21	76.0		NR		55.6
	HI	12	45.5		NR		55.6
	H	6	0.0		NR		NR
B symptoms	(−)	48	77.1	0.564	65.5	0.053	84.8	0.010
	(+)	25	70.8		56.9		55.4
Bulky sites	(−)	60	79.7	0.052	NR	0.314	69.9	0.414
	(+)	13	53.8		83.3		68.4

Values in bold highlight variables with significant p value.

† p-value cannot be calculated because of small numbers within some strata.

DFS: Disease-free survival; IPI: International prognostic index; LDH: LDH level; PS: Performance status; NR: Not reached; OS: Overall survival; ROC: Receiver operating characteristic.

Figure 1. Overall survival according to the mean of serum level of IL-18 (p = 0.008).

OS: Overall survival.

Figure 2. Overall survival according to serum level of sIL-2R (p = 0.001).

OS: Overall survival.

Figure 3. Overall survival according to International Prognostic Index (p = 0.001).

IPI: International prognostic index; OS: Overall survival.

Figure 4. Disease-free survival according to serum level of sIL-2R (p = 0.007).

DFS: Disease-free survival.

Figure 5. Disease-free survival according to clinical stage (p = 0.008).

DFS: Disease-free survival.

Table 4. Multivariate analyses on overall survival and disease-free survival.

Factor	HR	95% CI	p-value
Overall survival
sIL-2R (>592.4 U/ml)	11.41	2.5 – 52.4	0.022
Disease-free survival
sIL-2R (>592.4 U/ml)	4.1	1.0 – 16.5	0.057
Clinical stage (advanced stage)	3.5	0.9 – 12.8	0.047

Values in bold highlight variables with significant p-value.

HR: Hazard ratio.