TABLE 1 Baseline characteristics of patients with NHL-HLH
|
Included Cases (N = 153)
|
Demographic and clinical features
|
|
Median age (range), years
|
54 (41.5-64.5)
|
Age > 60 years
|
63/153 (41.2%)
|
Male
|
110/153 (71.9%)
|
Symptoms and signs at presentation
|
|
Fever (T ≥ 38.5℃)
|
153/153 (100%)
|
Splenomegaly
|
145/153 (94.8%)
|
Bicytopenia or pancytopenia
|
103/153 (67.3%)
|
Hypofibrinogenemia
|
84/153 (54.9%)
|
Hypertriglyceridemia
|
63/153 (41.2%)
|
Hemophagocytosis
|
132/153 (86.3%)
|
Serum ferritin (≥500ug/L)
|
151/153 (98.7%)
|
Serum ferritin (≥10000ug/L)
|
43/153 (28.1%)
|
Soluble IL-2 receptor (≥ 2400ng/L)
|
152/153 (99.3%)
|
Soluble IL-2 receptor (≥ 20000ng/L)
|
132/153 (86.3%)
|
Hepatomegaly
|
56/153 (36.6%)
|
Lymphadenopathy
|
121/153 (79.1%)
|
Diagnosis
|
|
T cell lymphoma
|
91/153 (59.5%)
|
NK/T cell lymphoma
|
49/153 (32.0%)
|
Peripheral T cell lymphoma, NOS
|
5/153 (3.3)
|
Anaplastic large cell lymphoma
|
1/153 (0.7%)
|
Angioimmunoblastic T cell lymphoma
|
3/153 (2.0%)
|
Unclassified
|
33/153 (21.6%)
|
B cell lymphoma
|
62/153 (40.5%)
|
Diffuse large B cell lymphoma
|
9/153 (5.9%)
|
Intravascular large B-cell lymphoma
|
2/153 (1.3%)
|
Chronic lymphoblastic leukemia/
small lymphocytic lymphoma
|
1/153 (0.7%)
|
Burkitt lymphoma
|
1/153 (0.7%)
|
Unclassified
|
49/153 (32.0%)
|
Stage Ⅲ/Ⅳ
|
140 (91.5%)
|
B symptoms
|
142 (92.8%)
|
IPI score
|
3.3 ± 0.7
|
TABLE 2 Comparison of clinical and laboratory characteristics of NHL-HLH patients with or without hyponatremia.
Variables
|
Overall
(N=153)
|
Sodium<135mmol/L
(N=81)
|
Sodium≥135mmol/L
(N=72)
|
P valuea
|
Sodium (mmol/L)b
|
134.4 (131.1-138)
|
131.6 (128.8-132.8)
|
138.2 (135.8-140.1)
|
<0.001
|
Gender (male)
|
110 (71.9)
|
61 (75.3)
|
49 (68.1)
|
0.319
|
Age (years)
|
54.0 (41.5-64.5)
|
54 (41.5-64.5)
|
57.5 (41.25-64.75)
|
0.988
|
ANC(×109/L)
|
1.06 (0.62-1.98)
|
1.08 (0.65-1.88)
|
1.19 (0.62-2.08)
|
0.737
|
HB (g/L)
|
83.0 (70.5-96.5)
|
84.0 (72.5-105)
|
80.0 (67.5-93.5)
|
0.132
|
PLT (×109/L)
|
40 (21-71)
|
38 (21-61)
|
45 (23-73)
|
0.226
|
FIB (g/L)
|
1.42 (0.93-2.12)
|
1.37 (0.86-2.01)
|
1.56 (1.05-2.31)
|
0.057
|
ALB (g/L)c
|
27.0±4.8
|
27.1±5.0
|
26.9±4.5
|
0.798
|
TG (mmol/L)
|
2.51 (1.74-3.84)
|
2.55 (1.75-3.74)
|
2.48 (1.64-4.03)
|
0.784
|
Chlorine (mmol/L)
|
99.9±5.9
|
96.8±5.1
|
103.6±4.7
|
<0.001
|
ADA (U/L)
|
77.9(47.4-106.8)
|
77.9 (56.9-120.8)
|
62.9 (41.9-83.4)
|
0.015
|
β2-MG (mg/L)
|
7.4 (5.2-7.8)
|
7.4 (5.3-7.9)
|
7.4 (5.1-7.5)
|
0.588
|
Ferritin (ug/L)
|
4009 (1493-13836)
|
6752 (2055-20000)
|
2345 (1109-20000)
|
<0.001
|
sCD25 (ng/L)
|
38096 (29100-51923)
|
38096 (31534-49654)
|
38096 (29100-51923)
|
0.762
|
Hscore
|
238 (200-274)
|
255 (207-274)
|
229 (190-277)
|
0.103
|
EBV infection
|
84 (54.9%)
|
51 (63.0%)
|
33 (45.8%)
|
0.034
|
Lymphoma type
|
|
|
|
0.01
|
B cell lymphoma
|
62 (40.5%)
|
25 (30.9%)
|
37 (51.4%)
|
|
T cell lymphoma
|
91 (59.5%)
|
56 (69.1%)
|
35 (48.6%)
|
|
Treatment
|
|
|
|
0.656
|
Chemotherapy±HLH-94
|
110 (71.9%)
|
57 (70.4%)
|
53 (73.6%)
|
|
HLH-94 or GC±IVIG
|
43 (28.1%)
|
24 (29.6%)
|
19 (26.4%)
|
|
Abbreviations: NHL-HLH, Non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis; ANC, absolute neutrophil count; HB, haemoglobin; PLT, Platelet; FIB, fibrinogen; ALB, albumin; LDH, lactate dehydrogenase; TG, triglyceride; ADA, adenosine deaminase; β2-MG, beta2-microglobulin; sCD25, Soluble IL-2 receptor; EBV, Epstein-Barr virus; GC, glucocorticoid, IVIG, intravenous immunoglobulin
aComparison between patients with Sodium<135mmol/L and Sodium≥135mmol/L.
bMedian and range were reported for continuous variables.
cMean and SD were reported for continuous variables.
TABLE 3 Univariate and multivariate Cox regression analyses of OS with NHL-HLH
Variables (Ref)
|
Univariate analysis
|
|
Multivariate analysis
|
HR (95%CI)
|
P Value
|
|
HR (95%CI)
|
P Value
|
Male (Female)
|
1.08(0.73-1.59)
|
0.713
|
|
|
|
Age > 60 years (≤ 60 years)
|
1.11 (0.77-1.59)
|
0.575
|
|
|
|
ANC < 1.0×109/L (≥1.0×109/L)
|
1.22 (0.85-1.75)
|
0.278
|
|
|
|
HB < 90g/L (≥ 90 g/L)
|
1.23 (0.85-1.79)
|
0.264
|
|
|
|
PLT < 100×109/L (≥100×109/L)
|
2.33 (1.22-4.47)
|
0.010
|
|
|
|
FIB ≤ 1.5g/L (> 1.5 g/L)
|
1.90 (1.31-2.74)
|
0.001
|
|
1.52 (1.03-2.25)
|
0.037
|
LDH ≥ 1×ULN (< 1×ULN)
|
1.51 (1.05-2.17)
|
0.025
|
|
|
|
ALB < 30g/L (≥ 30g/L)
|
1.69 (1.09-2.61)
|
0.018
|
|
|
|
TG ≥ 3.0mmol/L (< 3.0mmol/L)
|
1.43 (0.99-2.04)
|
0.053
|
|
|
|
Ferritin>10000ug/L(≤ 10000ug/L)
|
2.94 (1.99-4.34)
|
<0.001
|
|
2.31 (1.53-3.49)
|
<0.001
|
sCD25 >20000ng/L(≤20000 ng/L)
|
2.59 (1.41-4.75)
|
0.002
|
|
2.80 (1.49-5.24)
|
0.001
|
EBV infection (no EBV infection)
|
1.46 (1.01-2.09)
|
0.043
|
|
|
|
T cell lymphoma
(B cell lymphoma)
|
1.84 (1.27-2.68)
|
0.001
|
|
|
|
Chemotherapy±HLH-94
(HLH-94 or GC±IVIG)
|
0.36 (0.25-0.53)
|
<0.001
|
|
0.31 (0.21-0.46)
|
<0.001
|
Na+ < 135mmol/L (≥ 135mmol/L)
|
1.77 (1.23-2.54)
|
0.002
|
|
1.51 (1.03-2.20)
|
0.033
|
Abbreviations: Ref, ANC, absolute neutrophil count; HB, haemoglobin; PLT, Platelet; FIB, fibrinogen; LDH, lactate dehydrogenase; ALB, albumin; TG, triglyceride; sCD25, Soluble IL-2 receptor; EBV, Epstein-Barr virus; ULN, upper limit of normal