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Blood cytokine concentrations in ALK-positive ALCL
0 pg/mL, P=0.002), IP-10 (343.9 pg/mL versus 118.3 pg/mL, P=0.002), MIG (441.0 pg/mL versus 276.4 pg/mL, P=0.006), and sIL-2R (190649.2 pg/mL versus 82290.3 pg/mL, P=0.01) compared to patients without bone mar- row involvement.
The central nervous system was involved in two of the 116 patients who had a lumbar puncture. Both patients had high concentrations of IL-6 (170.9 pg/mL, 513.5 pg/mL) and IL-17a (2623.3 pg/mL, 1468.3 pg/mL).
Correlations of cytokine concentrations with other organ involvement (skin, mediastinum, liver, lung and spleen) are shown in Online Supplementary Table S4.
Patients in a poorer general condition (24/119) at the time of diagnosis (4 or 5 on a subjective scale from 1 to 5) had significantly higher concentrations of IL-1β (P=0.013), IL-6 (P<0.001), IL-10 (P<0.001), IL-12p70 (P=0.024), IL-17a (P<0.001), HGF (P<0.001), sIL-2R (P<0.001), VEGF (P=0.006), IFN-γ (P=0.039), and IP-10 (P=0.025) (Online Supplementary Figure S2).
B symptoms, leukocytosis, C-reactive protein, and lactate dehydrogenase levels
In comparison to patients without B symptoms, patients with B symptoms (63/119) had significantly high- er concentrations of IL-6 (P=0.001), IL-10 (P<0.001), IL 12p70 (P=0.024), IFN-γ (P=0.04), MIG (P=0.046), HGF (P=0.002), sIL-2R (P<0.001), sCD30 (P=0.002), and IP-10
(P=0.008), and lower median concentrations of G-CSF (P=0.035). Likewise, patients with CRP values above 4 mg/L (64/119) had significantly higher concentrations of sIL-2R (P<0.001), IL-6 (P<0.001), IL-10 (P=0.044), IL-17a (P=0.002), HGF (P=0.006), and sCD30 (P<0.001) than patients with a lower CRP.
Patients with lactate dehydrogenase values above 240 U/L (57/119) had significantly higher concentrations levels of sIL-2R (P<0.001), IP-10 (P=0.003), MIG (P<0.001), and sCD30 (P=0.008). Patients with leukocytosis (white blood cells: >10 x 109/L, 47/119) had significantly higher concen- trations of IL-1β (P=0.043), IL-17a (P<0.001), IL-6 (P=0.01), and HGF (P=0.003).
Histological subtype
Histological subtype was analyzed in 87 ALCL patients. The 37 patients with non-common histological subtype had significantly higher concentrations of IL-6 (13.2 pg/mL versus 0 pg/mL, P=0.047) and IL-17a (P=0.018) as compared to patients with a common histology.
Correlations of cytokine levels with biological characteristics
Minimal disseminated disease
Minimal disseminated disease, defined as a positive polymerase chain reaction for NPM-ALK transcripts in bone marrow or peripheral blood, was detected at diagno-
Figure 2. Cytokine levels correlated with minimal disseminated disease.
Logarithmic representation of cytokine levels in pg/mL of ALK-positive ALCL patients at time of diagnosis according to the detection of minimal disseminat- ed disease (positive n=55, negative n=46). G-CSF levels were higher in patients without minimal disseminated disease. Only cytokines for which significant dif- ferences were found are shown.
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