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Non-Hodgkin Lymphoma
Blood cytokine concentrations in pediatric patients with anaplastic lymphoma kinase- positive anaplastic large cell lymphoma
Ferrata Storti Foundation
Fabian Knörr,1* Christine Damm-Welk,1* Stephanie Ruf,1 Vijay Kumar Singh,1 Martin Zimmermann,2 Alfred Reiter1 and Wilhelm Woessmann1
1NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, Justus-Liebig University, Giessen and 2Department of Pediatric Hematology and Oncology, Children’s Hospital, Hannover Medical School, Germany
*FK and CDW contributed equally to this work.
Haematologica 2018 Volume 103(3):477-485
ABSTRACT
Patients with anaplastic lymphoma kinase-positive anaplastic large cell lymphoma often present with B-symptoms or hemophagocy- tosis and generate an anti-tumor immune response. Specific serum cytokine levels or profiles may reflect the tumor burden, non-specific immune stimulation by the tumor or differences in the strength of the patients’ anti-lymphoma immunity. We systematically correlated pre- treatment concentrations of 25 cytokines with clinical and biological characteristics in a well-characterized cohort of 119 uniformly treated pediatric patients with anaplastic large cell lymphoma. Fifteen patients with anaplastic large cell lymphoma in remission and 11 patients with low-stage B-cell lymphoma served as controls. Concentrations of inter- leukin-9, interleukin-10, interleukin-17a, hepatocyte growth factor, sol- uble interleukin-2 receptor, and soluble CD30 were significantly higher in initial sera of patients than in the sera of subjects from both control groups, indicating an anaplastic large cell lymphoma-type cytokine sig- nature. The levels of interleukin-6, interferon-γ, interferon γ-induced protein, and soluble interleukin-2 receptor correlated with the stage, initial general condition, minimal disseminated disease, anaplastic lym- phoma kinase-antibody titers, and the risk of relapse among patients with anaplastic lymphoma kinase-positive anaplastic large cell lym- phoma. Only interleukin-6 showed an independent prognostic value in multivariate analyses. Pre-treatment cytokine profiles in patients with anaplastic large cell lymphoma reflect a tumor signature as well as tumor burden and also differences in the strength of the patients’ immune response.
Introduction
Patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lym- phoma (ALCL) often present with B symptoms or a macrophage activation syn- drome indicating an inflammatory or immune reaction.1 In addition, ALK-positive ALCL elicits a specific host immune response, as indicated by the production of anti- ALK-autoantibodies,2 and a cellular immune response against ALK.3-6 In some aspects, the immune response in ALCL is comparable to that occurring in patients with Hodgkin lymphoma, in whom elevated serum cytokine levels have been described at the time of diagnosis.7,8
Elevated levels of serum cytokines as immune mediators, such as interleukin (IL)- 6, IL-8, IL-10, IL-17a, and IL-22, have also been shown in small series of ALK-positive ALCL patients.9,10 In vitro production of IL-6, IL-8 and interferon (IFN)-γ by an ALK- positive ALCL cell line HSC-M1 has been reported.11 Soluble CD30 (sCD30) and the soluble IL-2 receptor (sIL-2R) can be shed from ALCL cells and their levels were
Correspondence:
Christine.Damm-Welk@paediat.med.uni- giessen.de
Received: August 16, 2017. Accepted: December 7, 2017. Pre-published: December 14, 2017.
doi:10.3324/haematol.2017.177972
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/3/477
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haematologica | 2018; 103(3)
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