Page 123 - Haematologica3

Blood cytokine concentrations in ALK-positive ALCL
Discussion
The aim of this study was to describe pretreatment serum cytokine concentrations and correlate them with clinical and biological characteristics among pediatric patients with NPM-ALK-positive ALCL.
Although blood was collected at 51 different trial sites, serum or plasma was used depending on availability, the time from blood collection to freezing varied by several hours and the storage period differed considerably, the correlations found between cytokines and clinical charac- teristics such as IL-6 and the patients’ general condition (Table 1) are indicative of reliable measurements.
Elevated pretreatment cytokine levels in patients with ALCL compared to either post-treatment samples or other non-Hodgkin-lymphoma patients have been reported in two series of patients. Savan et al. found higher levels of IL-22 and IL-8 in nine of 11 untreated ALCL patients com- pared to post-treatment controls.9 Mellgren et al. recorded higher levels of IL-6, IL-10, MIP-1α, and sIL-2R in six pedi- atric ALCL patients at time of diagnosis compared to the levels in children with other non-Hodgkin lymphoma.10
Our systematic analysis of serum cytokine levels con- firmed and extended these findings in a large group of children with untreated NPM-ALK-positive ALCL. IL-9, IL-10, IL-17a, HGF, sIL-2R, and sCD30 levels form a kind
Table 2. Cytokines in univariate and multivariate analyses.
Minimal disseminated disease 101
Positive 55 31 Negative 46 6
AntiALK antibody titer 119
≤1/750 34 21 >1/750 85 21
Clinical risk (HR) 119
Standard risk 42 5 High risk 77 37
B symptoms 119
Positive 63 29 Negative 56 13
Histology 87
Non-common 37 17 Common 50 13
sIL-2R 119
>median 59 28 ≤median 60 14
IL-6 119
>0pg/mL 56 32 =0pg/mL 63 10
IL-10 119
>0pg/mL 53 27 =0pg/mL 66 15
2.9 ± 0.4
0.007
Univariate
Multivariate
< 0.001
< 0.001
0.005
Patients
Events
HR
6.0 ± 0.4
3.7 ± 0.3
6.5 ± 0.5
2.3 ± 0.3
2.2 ± 0.4
2.7 ± 0.3
5.0 ± 0.4
2.9 ± 0.3
2.5 ± 0.3
3.5 ± 0.3
2.3 ± 0.3
2.6 ± 0.3
2.5 ± 0.3
2.0 ± 0.3
P
<0.001
< 0.001
< 0.001
0.01
0.038
0.002
< 0.001
0.001
0.004
< 0.001
0.008
0.003
0.004
0.028
HR
6.6 ± 0.5
3.6 ± 0.4
4.5 ± 0.5
P
IL-17a 119
>0pg/mL 43 22 =0pg/mL 76 20
IFN-γ 119
>0pg/mL 29 18 =0pg/mL 90 24
IP-10 118
>median 59 27 ≤median 59 15
MCP1 119
>median 59 29 ≤median 60 13
HGF 119
>median 59 28 ≤median 60 14
sCD30 119
>median 60 27 ≤median 59 15
Stepwise regression was used to test whether cytokines have additional prognostic value having taken into account the known risk factors minimal disseminated disease, anti- ALK-antibody titer and clinical risk group.37 HR, hazard ratio.
haematologica | 2018; 103(3)
483