Central Nervous System Involvement in Patients with Diffuse Large B Cell Lymphoma: Analysis of the Risk Factors and Prognosis from a Single-Center Retrospective Cohort Study

Figures & data

Table 1 Univariate Analysis of Risk Factors for CNS Involvement

Clinical Features	CNS (n)	Non-CNS (n)	OR	95% CI	χ^2	P Value
Gender				(0.701–4.773)	1.738	0.187
Male	15	50	1.875
Female	8	50
Age (years)				(0.419–2.480)	0.005	0.943
≥60	11	47	1.034
<60	12	53
ECOG Score			3.756	(1.466–10.22)	7.652	0.006
>2	10	17
≤2	13	83
Bulky Disease				(0.022–1.393)	2.132	0.144
Yes	1	16	0.239
No	22	84
Extranodal Site Involvement			1.6	(0.599–4.054)	0.912	0.340
≥2	8	25
<2	15	75
Stage			4.25	(1.614–11.56)	8.649	0.003
III–-IV	17	40
I–II	6	60
IPI			3.892	(1.406–9.766)	8.087	0.005
>2	16	37
≤2	2	63
LDH>236 U/L			3.183	(1.299–8.026)	6.299	0.012
Yes	13	29
No	10	71
GCB/Non-GCB			0.516	(0.140–1.936)	0.879	0.348
GCB	3	32
Non-GCB	8	44
Bone marrow Involvement			1.409	(0.459–4.529)	0.303	0.582
Yes	4	13
No	19	87
Rituximab			0.898	(0.303–2.974)	0.032	0.858
YES	19	81
No	4	19
Dorubicin Liposome			0.235	(0.070–0.806)	5.603	0.018
Yes	3	39
No	20	61

Table 2 Multivariate Analysis of Risk Factors for CNS Involvement

Clinical Factors	P Value	Hazard Ratio (95% CI)
Gender(male/female)	0.186	2.173(0.688–6.862)
Age ≥60 years	0.411	0.605(0.183–2.003)
ECOG >2	0.111	3.166(0.767–13.057)
IPI >2	0.084	4.564(0.815–25.547)
Elevated LDH	0.030	4.035(1.147–14.195)
Stage I–II/III–IV	0.859	0.861(0.164–4.522)
Extranodal involvement ≥2	0.959	1.038(0.245–4.398)
Bulky disease	0.059	0.113(0.012–1.088)
No use of dorubicin liposome	0.051	0.241(0.058–1.004)

Table 3 Baseline Characteristics of 38 DLBCL Patients with CNS Involvement

Baseline Characteristics (at Time of Diagnosis)	n (%)
Age (years)	59.84±8.71^a
Gender
Male	26(68.4%)
Female	12(21.6%)
LDH
High (>236U/L)	15(42.9%)
Normal (≤236U/L)	23(57.1%)
Bulky Disease^b
Yes	9(7.1%)
No	29(92.9%)
Sites
CNS only	11(35.7%)
CNS and Systemic	27(64.3%)
Deep lesion^c
Yes	21(55.3%)
No	17(44.7%)
CSF Protein
>1.0g/L	13(43.3%)
≤1.0g/L	17(66.7%)
CSF Nuclear Cells
>8×10^6/L	10(32.3%)
≤8×10^6/L	21(67.7%)
CSF Lymphoma Cells
Positive	24(35.7%)
Negative	14(64.3%)
Eyes Involvement
Yes	7(7.1%)
No	31(92.9%)

Notes: ^aMean±SD; ^bBulky disease refers to the lesion diameter greater than 3 cm; ^cDeep lesions defined as lesions located more than 3 cm from the brain surface.

Table 4 Univariate Analysis of 38 DLBCL Patients with CNS Involvement

Clinical Factors	Median Survival (Months)	Number	Death (N)	HR 95% CI	χ^2	P Value
Gender				1.063(0.332–3.399)	0.011	0.918
Male	22	26	11
Female	NR	12	4
Age (years)				2.683(0940–7.663)	3.399	0.065
≥60	21	21	11
<60	NR	17	4
ECOG Score				5.215(1.842–14.76)	9.678	0.002
>2	8	19	13
≤2	NR	19	2
LDH>236 U/L				5.355(1.648–17.4)	7.789	0.005
Yes	8	15	9
No	NR	23	6
CSF Protein				10.84(2.165–54.32)	8.406	0.004
≥1.0 g/L	8	13	6
<1.0 g/L	NR	17	7
CSF Nuclear Cell				2.254(0.782–6.495)	2.265	0.132
>8×10^6/L	21	24	11
≤8×10^6/L	NR	14	4
Lymphocyte Count				8.857(1.999–39.25)	5.025	0.023
≤0.75×10^9/L	3.5	4	2
>0.75×10^9/L	31	34	13
White Blood Cell
3.5–9.5×10^9/L	NR	21	7		1.586	0.452
>9.5×10^9/L	21	10	4
<3.5×10^9/L	14	7	4
Neutrophil Count
1.8–6.3×10^9/L	NR	24	12		3.202	0.074
>6.3×10^9/L	NR	11	3
<1.8×10^9/L	21	3	0
Neutrophil (%)				1.269(0.424–3.793)	0.182	0.670
≥75%	NR	16	6
<75%	22	22	9
Lymphocyte (%)				2.483(0.862–7.153)	2.837	0.092
<20%	14	21	10
20–50%	NR	17	5
Bulky Disease				1.476(0.47–4.635)	0.254	0.614
Diameter ≥3 cm	21	9	4
Diameter <3 cm	31	29	11
Deep Lesion				2.745(0.960–7.852)	3.546	0.060
Yes	21	21	12
No	NR	17	3
Systemic Involvement with SCNS				1.357(0.410–4.488)	0.250	0.617
Yes	22	27	12
No	NR	11	3
Site of CNS Involvement					4.931	0.085
Parenchymal (incl. eye)	NR	21	6
Leptomeningeal Only	8	2	1
Both	8	15	8

Table 5 Multivariate Analysis of 38 DLBCL Patients with CNS Involvement

Clinical Factors	Std. Err.	Z Value	P Value	HR	95% CI
Age ≥60 years	0.861	0.053	0.951	1.054	(0.195–5.694)
ECOG >2	0.863	2.045	0.018	7.333	(1.424–42.002)
LDH >236 U/L	0.938	1.873	0.046	6.510	(1.035–40.949)
CSF protein >1.0g/L	0.507	0.642	0.206	1.900	(0.703–5.133)
Lymphocyte >0.75×10^9/L	1.406	−3.067	0.029	0.047	(0.003–0.732)
Lymphocyte (%) <20%	0.899	−0.308	0.732	0.735	(0.126–4.279)
Deep lesion	0.855	2.395	0.005	10.957	(2.050–58.569)
Neutrophil count <6.3109/L	1.025	−1.078	0.293	0.340	(0.046–2.538)
Site of Involvement (CNS + Systemic)	0.441	1.004	0.023	2.730	(1.151–6.479)

Figure 1 Kaplan–Meier curve of the median OS durations of 38 DLBCL patients after CNS involvement.

Figure 2 Kaplan–Meier curve of the median PFS durations of 38 DLBCL patients after CNS involvement.

Figure 3 Kaplan–Meier curve of OS time between 38 DLBCL patients with CNS involvement (SCNSL) and 100 DLBCL patients without CNS involvement.

Figure 4 Kaplan–Meier curve of OS time between 11 DLBCL patients with CNS involvement only and 27 DLBCL patients with extra-CNS involvement.

Figure 5 Kaplan–Meier curve of OS time between the 15 patients with CNS involvement at the time of DLBCL diagnosed and 23 patients with CNS involvement during or after first-line therapy.

Figure 6 Kaplan–Meier curve of OS time between the 38 patients with CNS involvement and 40 stage III-IV DLBCL cases without CNS involvement.