Existing models for predicting outcome in patients with Hodgkin lymphoma, including the International Prognostic Score (IPS), may be losing their accuracy and robustness, in light of recent improvements in treatment, increasing dose intensity, early recognition of toxicity, and enhanced supportive care for these patients, according to Kristie A. Blum, MD, of Ohio State University, Columbus.

The addition of biologic markers to recognized clinical prognostic factors, including the IPS, may improve risk stratification of these patients and guide therapy in the future. However, it has been difficult to fully establish these markers due to the lack of large confirmatory prospective trials and the inadequacy of the assays, she added.

Promising Biomarkers

One biomarker is emerging as quite promising, according to Dr. Blum. CD68 is present on tumor-infiltrating macrophages and detectable by immunohistochemical staining, and is significantly associated with shortened progression-free and disease-specific survival both at diagnosis and at relapse. In addition, the presence of less than 5% CD68-positive cells correlates with a 100% disease-specific survival in patients with early-stage Hodgkin lymphoma. In a multivariate analysis, CD68 expression was superior to the IPS in predicting disease-free survival.

"CD68 represents just one of the many prognostic markers that could eventually be used to risk-stratify therapy and may also serve as therapeutic targets in Hodgkin lymphoma," she said.

CD20 expression may be another biomarker. An increased number of tumor-infiltrating CD20-positive small B cells was associated with both prolonged progression-free and disease-free survival, although not all studies have validated this. Recent data suggest that an increased number of CD20-positive infiltrating B cells coupled with low CD68 expression on tumor-infiltrating macrophages may identify patients with very favorable Hodgkin lymphoma.

A variety of other prognostic markers have been described in the disease, although their value so far is not as strong. There is no current consensus on how best to use these markers along with current clinical prognostic risk factors or how to use them to alter treatment. This information will only become clear when they are incorporated into clinical trials. ■