Clinicopathologic characteristics of 342 patients with multicentric Castleman disease in Japan

Figures & data

Figure 1. Enrollment, disposition, and pathologic classification in patients with multicentric Castleman disease. Twenty-four patients previously received tocilizumab in the clinical trial or compassionate use for tocilizumab. Nine patients with misdiagnosed MCD (5 with malignant lymphoma, 2 with another malignancy, 1 with UCD, and 1 with autoimmune disease). *One patient was excluded for two reasons: one of the five patients with malignant lymphoma had also previously received tocilizumab.

Figure 2. Age at disease onset and duration of disease in patients with multicentric Castleman disease. The distributions of age at disease onset (A) and of disease duration (B) in male (A: n = 170, B: n = 172) and female (A: n = 114, B: n = 116) patients with MCD in available data. Dark gray bars indicate male patients and light gray bars indicate female patients.

Figure 3. Mean body weight, height, and body mass index of patients with multicentric Castleman disease compared with the general Japanese population. Differences in the mean body height (A, B), weight (C, D) and body mass index (E, F) between this study population and the general Japanese population [46]. The bar indicates standard deviation. Statistical analysis has not been performed because of a large difference in the sample size between this study population and the general Japanese population. Dark gray bars indicate the study population and light gray bars indicate the general Japanese population.

Table 1. Characteristics of the patients.

			No. of patients with available data
Sex	Male no.	202 (59.1%)	342
	Female no.	140 (40.9%)
Age	Mean ± SD	48.8 ± 13.3	342
	Median (min–max)	48.0 (3.0–84.0)
Family history	no.	0 (0%)	339
Age at disease onset, years	Mean ± SD	43.1 ± 13.4	284
	Median (min–max)	43.0 (2.0–82.0)
Duration of disease, years	Mean ± SD	5.5 ± 5.6	288
	Median (min–max)	3.7 (0.0–30.3)
Severe idiopathic MCD^a	no.	108 (31.6%)	342
Body weight, kg	Mean ± SD	58.1 ± 12.1	319
	Median (min–max)	57.5 (13.0–104.0)
BMI, kg/m^2	Mean ± SD	21.8 ± 3.5	277
	Median (min–max)	21.6 (14.4–37.3)
Medical history	no.	159 (46.8%)	340
Previous chemotherapy^b	no.	27 (7.9%)	342
Steroids (oral + injection)^c	no.	250 (73.1%)	342
Steroid dose, mg/day (oral + injection)	Mean ± SD	21.8 ± 29.6	248^d/250
	Median (min–max)	15.0 (1.0–377.5)
Steroid dose, mg/kg/day (oral + injection)	Mean ± SD	0.4 ± 0.5	237^d/250
	Median (min–max)	0.3 (0.01–4.98)

BMI: body mass index; max: maximum; min: minimum; SD: standard deviation.

^a Severity was assessed using the consensus guideline for treatment of idiopathic MCD, which defines severity criteria of idiopathic MCD [25].

^b Number of patients treated with any chemotherapy or immunosuppressants in the 3 months before enrollment. The details are as follows: cyclophosphamide 16, vincristine 4, azathioprine 3, doxorubicin 3, rituximab 3, melphalan 2, methotrexate 2, cyclosporin 1, and mizoribine 1. Two patients were with cyclophosphamide, doxorubicin, and vincristine; one was treated with rituximab, cyclophosphamide, doxorubicin, and vincristine; and one was treated with cyclophosphamide and vincristine.

^c Number of patients treated with a steroid in the 3 months before enrollment.

^d Number of steroid-use patients with available data.

Table 2. Clinical features (≥2.0%).

Clinical features	All patients (N = 342)
Lymphadenopathy, no	342	(100.0%)
Clinical features except for lymphadenopathy, no.	336	(98.2%)
Liver disorder^a	108	(31.6%)
Hepatomegaly	91	(26.6%)
Hepatic function abnormal	18	(5.3%)
Ascites	7	(2.0%)
Kidney and urologic disorder	113	(33.0%)
Renal failure	28	(8.2%)
Glomerulonephritis	25	(7.3%)
Renal function test abnormalities	19	(5.6%)
Proteinuria	18	(5.3%)
Hematuria	13	(3.8%)
Renal amyloidosis	12	(3.5%)
Nephrotic syndrome	7	(2.0%)
Tubulointerstitial nephritis	7	(2.0%)
Heart disease^b	63	(18.4%)
Electrocardiograph abnormalities	53	(15.5%)
Cardiac failure	11	(3.2%)
Respiratory disorder^c	168	(49.1%)
Pulmonary involvement	146	(42.7%)
Asthma	10	(2.9%)
Pleural effusion	9	(2.6%)
Infection^d	34	(9.9%)
Other^e	326	(95.3%)
Fatigue	211	(61.7%)
Splenomegaly	143	(41.8%)
Rash	80	(23.4%)
Hypertension	73	(21.3%)
Pyrexia	59	(17.3%)
Diabetes mellitus	53	(15.5%)
Decreased appetite	52	(15.2%)
Night sweats	43	(12.6%)
Hyperuricemia	37	(10.8%)
Secondary amyloidosis^f,^g	34	(9.9%)
Insomnia	22	(6.4%)
Anemia	21	(6.1%)
Back pain	20	(5.8%)
Constipation	20	(5.8%)
Osteoporosis	19	(5.6%)
Neurosis	15	(4.4%)
Iron deficiency anemia	13	(3.8%)
Gastric ulcer	10	(2.9%)
Hypothyroidism	11	(3.2%)
Dyslipidemia	13	(3.8%)
Allergy	20	(5.8%)
Platelet count decreased	8	(2.3%)

^a Including bilirubin increased, autoimmune hepatitis, hemangioma of liver, and hepatic steatosis.

^b Including ventricular hypertrophy, pericardial effusion, and ischemic heart disease.

^c Including pulmonary hypertension, epistaxis, and lung cyst.

^d Including candidiasis, pneumonia, HIV infection, Epstein–Barr virus infection, tuberculosis, atypical mycobacterial infection, human T-cell leukemia virus type 1 (HTLV-1) carrier, and aspergillus infection.

^e Including edema, depression, myelodysplastic syndrome, arthritis, uveitis, hemolytic anemia, cerebrovascular disorder, neuropathy peripheral, convulsion, cryoglobulinemia, xanthelasma, hyperviscosity syndrome, and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome.

^f Including renal amyloidosis, gastrointestinal amyloidosis, cardiac amyloidosis, and hepatic amyloidosis.

^g 12 patients with renal amyloidosis included.

Figure 4. Results of laboratory tests in patients with multicentric Castleman disease: correlation with IL-6. Laboratory tests included albumin (Alb; A), hemoglobin (Hb; B), triglycerides (TG; C), total cholesterol (T-cho; D), C-reactive protein (CRP; E), fibrinogen (Fib; F), immunoglobulin G (IgG; G), immunoglobulin A (IgA; H); immunoglobulin M (IgM; I), platelets (PLT; J), estimated glomerular filtration rate-normalized body surface area (eGFR-NOR; K). r indicates the Spearman’s product-moment correlation coefficient.

Table 3. Laboratory tests associated with multicentric Castleman disease.

Laboratory test	No. of patients	Mean (SD)	Median (min–max)
Albumin, g/dL	256	2.5 (0.7)	2.5 (0.5–4.3)
Hemoglobin, g/dL	324	9.1 (2.2)	9.0 (4.5–15.6)
Triglyceride, mg/dL	216	72.9 (42.5)	61.0 (22.0–293.0)
Total cholesterol, mg/dL	246	124.2 (43.2)	117.0 (51.0–320.0)
C-reactive protein, mg/L	340	75.0 (52.8)	67.8 (0.0–375.5)
Fibrinogen, mg/dL	190	580.1 (172.9)	575.5 (1.5–1181.0)
IgG, mg/dL	278	4620.5 (2156.2)	4572.0 (523.0–10070.0)
IgA, mg/dL	265	586.0 (334.0)	531.0 (25.0–1741.0)
IgM, mg/dL	264	314.8 (286.0)	241.5 (32.0–2621.0)
Platelets, 10^3/µL	337	328.7 (169.1)	324.0 (5.0–1117.0)
eGFR-NOR, mL/min/1.73 m^2	285	78.8 (60.8)	76.0 (4.3–823.3)
Interleukin-6, pg/mL	59	39.0 (61.4)	20.1 (2.8–326.0)

eGFR-NOR: estimated glomerular filtration rate-normalized body surface area; IgA: immunoglobulin A; IgG: immunoglobulin G; IgM: immunoglobulin M; max: maximum; min: minimum; SD: standard deviation.

Table 4. Laboratory tests: Spearman’s correlation coefficient with IL-6.

Laboratory test	No. of patients	r
Albumin, g/dL	48	−0.59
Hemoglobin, g/dL	58	−0.59
Triglyceride, mg/dL	42	−0.38
Total cholesterol, mg/dL	50	−0.29
C-reactive protein, mg/L	59	0.58
Fibrinogen, mg/dL	39	0.28
IgG, mg/dL	53	0.29
IgA, mg/dL	51	0.17
IgM, mg/dL	51	−0.20
Platelets, 10^3/µL	59	0.03
eGFR-NOR, mL/min/1.73 m^2	53	−0.06

r: the Spearman’s product-moment correlation coefficient with IL-6; IgG: immunoglobulin G; IgA: immunoglobulin A; IgM: immunoglobulin M; and eGFR-NOR: estimated glomerular filtration rate-normalized body surface area.

Ministry of Health, Labour and Welfare. Japanese Government Statistics. Trends in mean height, body weight and body mass index in 2012.

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van Rhee F, Voorhees P, Dispenzieri A, Fossa A, Srkalovic G, Ide M, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115–24.

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