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 d iscussion, and no assays are available to distinguish potential respon ders from nonresponders. Herein we analyzed the usefulness of serum tu mor necrosis factor (TNF, a cytokine released by CLL cells) and MxA pr otein (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 expres sion were determined at diagnosis in 21 CLL patients, A statistically significant correlation was found between low TNF levels and MxA expre ssion and between high TNF levels and no measurable MxA expression, Th e 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 patie nts 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 l onger survival without therapy, More patients have to be tested to str engthen the value of MxA expression and TNF concentrations for subsequ ent response to IFN-alpha therapy.