Discriminant analysis involving serum cytokine levels and prediction of the response to therapy of patients with Hodgkin lymphoma

Abstract

Current standard diagnostic methods do not identify patients with Hodgkin lymphoma (HL), who are at high risk of failure after the first-line treatment. In HL patients, serum cytokine levels are frequently elevated and correlate with clinical and pathological features of the disease as well as with disease-free survival and overall survival. The aim of this study was to investigate if pretreatment serum cytokine and cytokine receptor concentrations evaluated by discriminant analysis could be predictive of response to standard first-line treatment in HL. The study involved 48 previously untreated patients with histologically confirmed classical HL and no EBV infection. Treatment included chemotherapy and involved field radiotherapy or radiotherapy alone. At the end of treatment, 71 % of patients reached complete response (CR), and 29 %, in partial response. To identify parameters predictive of nonachievement of CR after the first-line treatment, the discriminant analysis was used. The following variables were included in the analysis: clinical stage, sex, age, histologic subtype, bulky mediastinal mass, systemic symptoms and the number of involved nodal areas, lactate dehydrogenase (LDH) activity, and serum levels of 12 cytokines/cytokine receptors. The resulting classifying function assigned a discriminant power to the following variables: the levels of vascular endothelial growth factor, interleukin-8, macrophage colony stimulating factor, basic fibroblast growth factor, soluble tumor necrosis factor receptor I, and LDH activity. The accuracy of predicting CR and non-CR was 94 and 43 %, respectively.

High CD206 levels in Hodgkin lymphoma‐educated macrophages are linked to matrix‐remodeling and lymphoma dissemination

“…We propose that M‐CSF induces a network of signaling pathways to activate autocrine Mφ differentiation factors, whereas IL13 directly promotes an early differentiation program. Although elevated M‐CSF serum levels have been reported in HL patients, and HL cells were found to be M‐CSF‐positive by immunohistochemistry, the measured M‐CSF amounts in the lymphoma‐CM in vitro and the differences in Mφ counts and phenotype indicate the involvement of additional factors during HL‐specific Mφ differentiation (Casagrande et al , ; Kowalska et al , ; Zheng et al , ). Recently, an autoregulatory loop between TAMs and breast cancer cells has been reported (Cassetta et al , ).…”

Neutrophil Death in Myeloproliferative Neoplasms: Shedding More Light on Neutrophils as a Pathogenic Link to Chronic Inflammation

“…Arnold and Kahwash [148] in their work described bone marrow macrophages containing neutrophils or neutrophil nuclear fragments, significantly associated with malignancy (when compared to bone marrow biopsies for nonneoplastic conditions), in particular Hodgkin lymphoma, which they called "fragmentophages". Hodgkin lymphoma is known to be associated with increased production of cytokines, such as IL-6 and IL-10 [149], VEGF, IL-8, bFGF as well as LDH activity [150], and myeloid hyperplasia in the bone marrow [148], the conditions similar to those seen in MPN.…”

Angiogenesis in Hodgkin’s lymphoma

“…In the future, this could lead to the identification of groups of patients who should be considered for reduction of treatment intensity in order to avoid the side effects associated with oncological treatment, or the use of a more aggressive therapeutic approach in patients at high risk of relapse. The observation that high levels of VEGF in the blood serum HL are associated with a poor prognosis suggests that VEGF may be a new prognostic factor [13,14].…”