Treatment strategies for early-stage chronic lymphocytic leukemia: can interferon-inducible MxA protein and tumor necrosis factor play a role as predictive markers for response to interferon therapy?

The potential benefit of interferon (IFN)-alpha therapy in early-stage B cell chronic lymphocytic leukemia (B-CLL) patients is still under discussion, and no assays are available to distinguish potential responders from nonresponders. Herein we analyzed the usefulness of serum tumor necrosis factor (TNF, a cytokine released by CLL cells) and MxA protein (an intracellular marker for biologic activity of endogenous IFN) concentrations as predictive measurements for evolution and response to IFN therapy in early-stage CLL patients. TNF levels and MxA expression were determined at diagnosis in 21 CLL patients. A statistically significant correlation was found between low TNF levels and MxA expression and between high TNF levels and no measurable MxA expression. The patients were then randomized to receive IFN-alpha or no therapy and were evaluated for response and evolution. When response to IFN-alpha therapy was considered, it became apparent that early-stage CLL patients with higher TNF levels and no measurable MxA expression were more likely to benefit from IFN therapy, whereas those patients with lower TNF levels and MxA expression could be considered CLL candidates for longer survival without therapy. More patients have to be tested to strengthen the value of MxA expression and TNF concentrations for subsequent response to IFN-alpha therapy.