Analysis of albumin as a prognostic factor in HHV-8/HIV-negative Castleman disease from a multicenter study

Figures & data

Figure 1. Flowchart review of the literature. Abbreviation. OS: overall survival.

Table 1. Clinical characteristics of the study population according to albumin (230 cases).

	Total		<30 g/L		30–40 g/L		≥40 g/L
	N	N (%)	N	N (%)	N	N (%)	N	N (%)	p value
Age (years)	230		24		59		147		0.023
≤ 40		123 (53.5)		12 (50.0)		23 (39.0)		88 (59.9)
> 40		107 (46.5)		12 (50.0)		36 (61.0)		59 (40.1)
Gender	230		24		59		147		0.734
Male		122 (53.0)		11 (45.8)		31 (52.5)		80 (54.4)
Female		108 (47.0)		13 (54.2)		28 (47.5)		67 (45.6)
Ethnicity	230		24		59		147		0.202
Asia		180 (78.3)		23 (95.8)		50 (84.7)		107 (72.8)
White		33 (14.3)		1 (4.2)		6 (10.2)		26 (17.7)
Black		6 (2.6)		0 (0.0)		1 (1.7)		5 (3.4)
Other		11 (4.8)		0 (0.0)		2 (3.4)		9 (6.1)
Pathology	230		24		59		147		<0.001
HV		161 (70.0)		7 (29.2)		30 (50.8)		124 (84.4)
PC		62 (27.0)		16 (66.7)		27 (45.8)		19 (12.9)
MIX		7 (3)		1 (4.2)		2 (3.4)		4 (2.7)
UCD/iMCD	230		24		59		147		<0.001
UCD		147 (63.9)		8 (33.3)		25 (42.4)		114 (77.6)
iMCD		83 (36.1)		16 (66.7)		34 (57.6)		33 (22.4)
B symptom	230	46 (20.0)	24	12 (50.0)	59	19 (32.2)	147	15 (10.2)	<0.001
Luminal effusion	179	15 (8.4)	23	5 (21.7)	50	6 (12.0)	106	4 (3.8)	0.010
Hepatosplenomegaly	230	30	24	8(33.3)	59	16(27.1)	147	6(4.1)	<0.001
Mass
Mass (mm)	193	46.8 ± 20.5	19	45.5 ± 20.5	43	44.2 ± 19.1	131	47.8 ± 21.0	0.582
Mass > 5 cm	193	76 (39.2)	19	7 (36.8)	43	17 (39.5)	131	52 (39.4)	0.976
WBC（×10^9/L）	224		24		59		141		0.074
≤4		11 (4.9)		3 (12.5)		2 (3.4)		6 (4.3)
4–10		184 (82.1)		16 (66.7)		46 (78.0)		122 (86.5)
>10		29 (12.9)		5 (20.8)		11 (18.6)		13 (9.2)
Hemoglobin (g/L)	224		24		59		141
≤120		67 (29.9)		19 (79.2)		26 (44.1)		22 (15.6)	<0.001
≤100		33 (14.7)		17 (70.8)		11 (18.6)		5 (3.5)	<0.001
PLT（×10^9/L）	224		24		59		141		0.006
≤100		7 (3.1)		2 (8.3)		3 (5.1)		2 (1.4)
100–300		160 (71.4)		10 (41.7)		41 (69.5)		109 (77.3)
>300		57 (25.4)		12 (50.0)		15 (25.4)		30 (21.3)
Elevated LDH	172	14 (8.1)	14	1 (7.1)	44	4 (9.1)	114	9 (7.9)	0.960
Elevated β2-MG	62	25 (40.3)	6	2 (33.3)	18	16 (88.9)	38	7 (18.4)	<0.001
Elevated ESR	60	31 (51.7)	6	3 (50.0)	19	15 (78.9)	35	13 (37.1)	0.013
Elevated CRP	107	29 (27.1)	7	4 (57.1)	29	15 (51.7)	71	10 (14.1)	<0.001

Significant p values are in bold.

Abbreviations. HV: hyaline-vascular; PC: plasma cell; MIX: mixed cellular variant; UCD: unicentric castleman disease; iMCD: human immunodeficiency virus– and human herpesvirus 8–negative multicentric Castleman disease, idiopathic MCD; Luminal effusion: ascites and/or pleural effusion and/or pericardial effusion; WBC: white blood cell count; PLT: platelets; LDH: lactate dehydrogenase, IU/L; β2-MG: β2-microglobulin, mg/L; ESR: erythrocyte sedimentation rate, mm/hr; CRP: C-reactive protein, mg/dL.

Table 2. Univariate analyses of overall survival of 230 patients with CD.

Clinical factor	Total			UCD			iMCD
	N	N of event (%)	p value	N	N of event (%)	p value	N	N of event (%)	p value
Gender			0.183			0.847			0.231
Male	122	13 (10.7)		82	3 (3.7)		40	10 (25.0)
Female	108	18 (16.7)		65	2 (3.1)		43	16 (37.2)
Age			0.011			0.381			0.036
≤ 40	123	10 (8.1)		90	4 (4.4)		33	6 (18.2)
> 40	107	21 (19.6)		57	1 (1.8)		50	20 (40.0)
Ethnicity			0.179			0.259			0.085
Asia	180	28 (15.6)		118	4 (3.4)		62	24 (38.7)
White	33	1 (3.0)		20	0 (0.0)		13	1 (7.7)
Black	6	0 (0.0)		3	0 (0.0)		3	0 (0.0)
Other	11	2 (18.2)		6	1 (16.7)		5	1 (20.0)
Pathology			<0.001			0.783			0.013
HV	161	7 (3.1)		131	4 (3.1)		30	3 (10.0)
PC	62	23 (37.1)		12	1 (8.3)		50	22 (44.0)
MIX	7	1 (14.3)		4	0 (0.0)		3	1 (50.0)
B symptom			<0.001			0.045			0.053
Yes	46	17 (37.0)		11	2 (18.2)		35	15 (42.9)
No	184	14 (7.6)		136	3 (2.2)		48	11 (22.9)
Luminal effusion			<0.001			0.741			0.004
Yes	15	9 (60.0)		3	0 (0.0)		12	9 (75.0)
No	164	19 (11.6)		114	4 (3.5)		50	15 (30.0)
Hepatosplenomegaly			<0.001			0.639			0.001
Yes	30	14 (46.7)		5	0 (0.0)		25	14 (56.0)
No	200	17 (8.5)		142	5 (3.5)		58	12 (20.7)
Mass > 5 cm			0.170			0.498			0.473
Yes	76	5 (6.6)		61	2 (3.3)		15	3 (20.0)
No	117	15 (12.7)		74	2 (2.7)		44	13 (29.5)
WBC ( ×10^9/L)			0.057			0.670			0.140
≤4	11	3 (27.2)		5	0 (0.0)		6	3 (50.0)
4–10	184	20 (10.9)		123	5 (4.1)		61	15 (24.6)
>10	29	7 (24.1)		14	0 (0.0)		15	7 (46.7)
Hemoglobin (g/L)			<0.001			0.256			0.009
≤120	67	19 (28.4)		29	2 (6.9)		38	17 (44.7)
>120	157	12 (7.6)		113	4 (3.5)		44	8 (18.2)
PLT（×10^9/L）			0.047			0.340			0.890
≤100	7	2 (28.6)		2	0 (0.0)		5	2 (40.0)
100–300	160	17 (10.6)		116	4 (3.4)		44	13 (29.5)
>300	57	12 (21.1)		24	2 (8.3)		33	10 (30.3)
Elevated LDH			0.746			0.575			0.870
Yes	14	2 (14.3)		6	0 (0.0)		8	2 (25.0)
No	158	18 (11.4)		100	5 (5.0)		58	13 (22.4)
Elevated β2-MG			0.154			0.245			0.144
Yes	37	10 (27.0)		10	0 (0.0)		27	10 (37.0)
No	25	3 (12.0)		16	2 (12.5)		9	1 (11.1)
Elevated ESR			0.011			0.763			0.013
Yes	32	9 (28.1)		10	1 (10.0)		22	8 (38.1)
No	28	1 (3.4)		15	1 (6.7)		13	0 (0.0)
Elevated CRP			0.010			0.999			0.075
Yes	29	7 (24.1)		15	0 (0.0)		14	7 (50.0)
No	78	5 (6.4)		55	0 (0.0)		23	5 (21.7)

Significant p values are in bold.

Abbreviations. HV: hyaline-vascular; PC: plasma cell; MIX: mixed cellular variant; CD: castleman disease; UCD: unicentric castleman disease; iMCD: human immunodeficiency virus– and human herpesvirus 8–negative multicentric Castleman disease, idiopathic MCD; Luminal effusion: ascites and/or pleural effusion and/or pericardial effusion; WBC: white blood cell count; PLT: platelets; LDH: lactate dehydrogenase, IU/L; β2-MG: β2-microglobulin, mg/L; ESR: Erythrocyte sedimentation rate, mm/hr; CRP: C-reactive protein, mg/dL.

Figure 2. Albumin and the HRs for all-cause death. (a) In the whole CD patients. (b) In the iMCD patients. Abbreviations. HR: hazard ratio; CD: Castleman disease; iMCD: human immunodeficiency virus- and human herpesvirus 8-negative multicentric Castleman disease, idiopathic MCD.

Table 3. Relationship between albumin and death in patients with CD.

Albumin, g/L	N	Model 1		Model 2		Model 3
		HR (95% CI)	p value	HR (95% CI)	p value	HR (95% CI)	p value
Per 1 unit decrease	230	0.88 (0.84, 0.91)	<0.001	0.87 (0.83, 0.91)	<0.001	0.91 (0.86, 0.97)	0.004
Albumin, g/L
<30	24 (12)	19.83 (6.96, 56.48)	<0.001	20.33 (7.12, 58.09)	<0.001	7.25 (1.89, 27.84)	0.032
30–40	59（14）	7.96 (2.86, 22.14)	<0.001	6.84 (2.45, 19.15)	<0.001	3.48 (1.11, 10.89)	0.004
≥40	147（5）	Reference		Reference		Reference

Significant p values are in bold.

Model 1. Crude model.

Model 2. Adjusted for age, gender.

Model 3. As model 2, and additionally adjusted for pathology, UCD/iMCD, hemoglobin, B symptom, Luminal effusion, Hepatosplenomegaly.

Abbreviations, HR: hazard ratio; CI: confdence interval; CD: castleman disease; UCD: unicentric castleman disease; iMCD: human immunodeficiency virus– and human herpesvirus 8–negative multicentric Castleman disease, idiopathic MCD.

Table 4. Relationship between albumin and death in patients with iMCD.

Albumin, g/L	N	Model 1		Model 2		Model 3
		HR (95% CI)	p value	HR (95% CI)	p value	HR (95% CI)	p value
Per 1 unit decrease	83	0.90 (0.86, 0.95)	<0.001	0.89 (0.84, 0.95)	<0.001	0.91 (0.85, 0.98)	0.012
Albumin, g/L
<30	16（10）	8.88 (2.42, 32.55)	0.001	9.03 (2.44, 33.32)	0.001	6.15 (1.29, 29.29)	0.023
30–40	34（13）	4.52 (1.28, 15.90)	0.019	3.99 (1.11, 14.31)	0.034	3.40 (0.84, 13.84)	0.087
≥40	33（3）	Reference		Reference		Reference

Significant p values are in bold.

Model 1: Crude model.

Model 2: Adjusted for age, gender.

Model 3: As model 2, and additionally adjusted for pathology, hemoglobin, B symptom, Luminal effusion, Hepatosplenomegaly.

Abbreviations. HR: hazard ratio; CI: confdence interval; iMCD: human immunodeficiency virus– and human herpesvirus 8–negative multicentric Castleman disease, idiopathic MCD.

Figure 3. Subgroup analyses of the effect of albumin on the risk of death. Each subgroup analysis adjusted, if not stratified, for gender, age, UCD/iMCD, B symptom, luminal effusion, hepatosplenomegaly, mass, WBC, hemoglobin, and PLT. Abbreviations. UCD: unicentric castleman disease; iMCD: human immunodeficiency virus- and human herpesvirus 8-negative multicentric Castleman disease, idiopathic MCD; Luminal effusion: ascites and/or pleural effusion and/or pericardial effusion; WBC: white blood cell count; PLT: platelets. CI confidence interval.

Figure 4. Survival curves of albumin in patients with CD. (a) In all CD patients. (b) In iMCD patients. (c) In UCD patients. Abbreviations. HR: hazard ratio; CD: castleman disease; UCD: unicentric castleman disease; iMCD: human immunodeficiency virus- and human herpesvirus 8-negative multicentric Castleman disease, idiopathic MCD.