Biological markers may add to prediction of outcome achieved by International Prognostic Score in Hodgkin's disease

Department of Medicine, Karolinska Hospital and Institutet, Stockholm, Sweden.
Annals of Oncology (Impact Factor: 7.04). 12/2000; 11(11):1405-11. DOI: 10.1023/A:1026551727795
Source: PubMed


The International Prognostic Score (IPS) identifies seven independent factors predicting progression-free and overall survival in advanced stage Hodgkin's disease (HD). The IPS is also applicable in limited disease. However, the IPS does not identify patients with a very poor prognosis. The aim of this study was to define biological markers which may add to the IPS in predicting outcome.
One hundred forty-five patients (> 15 years) with HD of all stages and histopathology subgroups were included. In addition to factors included in the IPS, serum levels of CRP, sCD4, sCD8, sCD25, sCD30, sCD54, interleukin (IL)-10, beta2-microglobulin and thymidine kinase were analysed.
The strongest predictors of a poor cause-specific survival (CSS) in univariate analyses were: increased serum levels of IL-10, sCD30 and CRP, anaemia, low levels of albumin (P < 0.001); stage IV (P = 0.003), age > or = 45 years (P = 0.006), increased serum levels of sCD25 (P = 0.010), low lymphocyte counts (P = 0.020). Serum IL-10 added prognostic information to that achieved by the IPS: patients with a high score and increased serum IL-10 had a very poor outcome with a five-year CSS of 38%. Patients with increased serum levels of sCD30 and a high score also had a poor outcome with a five-year CSS of 54%.
Serum levels of IL-10 and sCD30 may add to IPS in prediction of outcome in HD, and should be validated in large, prospective studies.

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Available from: Ulla Axdorph,
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    • "Elevated serum IL-10 levels have been found in up to 50% of HL patients and have been associated with inferior failure free survival (FFS) and overall survival (OS) in patients treated with ABVD or BEACOPP chemotherapy (Rautert et al., 2008; Sarris et al., 1999; Vassilakopoulos et al., 2001; Viviani et al., 2000). Elevated serum IL-10 levels confer a poor survival and may add to the prognostic value of the IPS in prediction of outcomes in HL (Axdorph et al., 2000). CCL17/TARC is a chemokine secreted by H/RS cells and its chemotactic properties may explain the infiltration of reactive T lymphocytes in HL (Niens et al., 2008; Peh et al., 2001; van den Berg et al., 1999). "

    Hodgkin's Lymphoma, 02/2012; , ISBN: 978-953-51-0402-5
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    • "The relative tumour burden obtained from radiologically measurable tumour burden normalized to body surface area is also promising (Gobbi, 2002). Soluble CD30 might also correlate with the number of HRS cells and correlates with prognosis (Axdorph et al., 2000; Christiansen et al., 1995; Enblad G, 1997; Nadali et al., 1998; Nadali et al., 1994). Different factors reflecting the growth characteristics of the HRS cells are prognostic factors (Zander et al., 2002). "
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    ABSTRACT: Hodgkin lymphoma (HL) is characterised histologically by a minority of malignant Hodgkin and Reed-Sternberg (HRS) cells surrounded by benign cells, and clinically by a relatively good prognosis. The treatment, however, leads to a risk of serious side effects. Knowledge about the biology of the disease, particularly the interaction between the HRS cells and the surrounding cells, is essential in order to improve diagnosis and treatment. HL patients with abundant eosinophils in the tumours have a poor prognosis, therefore the eosinophil derived protein eosinophil cationic protein (ECP) was studied. Serum-ECP (S-ECP) was elevated in most HL patients. It correlated to number of tumour eosinophils, nodular sclerosis (NS) histology, and the negative prognostic factors high erythrocyte sedimentation rate (ESR) and blood leukocyte count (WBC). A polymorphism in the ECP gene (434(G>C)) was identified and the 434GG genotype correlated to NS histology and high ESR. The poor prognosis in patients with abundant eosinophils in the tumours has been proposed to depend on HRS cell stimulation by the eosinophils via a CD30 ligand (CD30L)-CD30 interaction. However, CD30L mRNA and protein were detected in mast cells and the predominant CD30L expressing cell in HL is the mast cell. Mast cells were shown to stimulate HRS cell lines via CD30L-CD30 interaction. The number of mast cells in HL tumours correlated to worse relapse-free survival, NS histology, high WBC, and low blood haemoglobin. Survival in patients with early and intermediate stage HL, diagnosed between 1985 and 1992, was generally favourable and comparatively limited treatment was sufficient to produce acceptable results for most stages. The majority of relapses could be salvaged. Patients treated with a short course of chemotherapy and radiotherapy had an excellent outcome. In conclusion prognosis is favourable in early and intermediate stages and there are possibilities for further improvements based on the fact that mast cells and eosinophils affect the biology and prognosis of HL.
    Upsala Journal of Medical Sciences 01/2004; 109(3):179-228. · 1.98 Impact Factor
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    • "Using markers of potential tumour-biological importance, it will be possible to add prognostic information beyond that given by clinico-pathological variables and thereby, hopefully, diminish the risk of treatment failure. Such biological markers reported are, for example, infiltration of eosinophils into tumour tissue correlating serum levels of eosinophil cationic protein (ECP) (Enblad, 1993, Axdorph 2001, von Wasielewski, 2000, Molin, 2001), infiltration of mast cells (Molin, 2001), S-IL10 (Axdorph, 2000), beta-2 microglobulin (Dimopoulos, 1993), S-IL2 R (Enblad, 1995), and S-CD30 (Enblad, 1997). The difficulty is, however, proper validation of this information, since the markers often correlate and only add limited information to the prognostic information of other already known factors. "

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