Heterogeneity of HVR-1 quasispecies is predictive of early but not sustained virological response in genotype 1b-infected patients undergoing combined treatment with PEG- or STD-IFN plus RBV.

ISDR mutation pattern and HVR-1 quasispecies were analyzed in HCV genotype 1b-infected patients treated with either PEG- or STD-IFN plus ribavirin, in order to find virological correlates of therapy outcome. ISDR region analysis, performed at baseline (T0) and at 4 weeks of therapy (T1), indicated that ISDR mutation pattern was not predictive of response to treatment. Moreover, no selection of putative resistant strains in the first month of therapy was observed. Viral load was not correlated with any parameter of HVR-1 heterogeneity. Among the HVR-1 heterogeneity parameters considered, complexity was inversely correlated to viral load decline at T1. In univariate analysis, complexity, proportion of non synonymous substitutions (NS) and NS/S ratio were lower in patients showing virological response at 6 months of treatment. Complexity was the only parameter independently associated with both decline of viral load at T1 and virological response after 6 months, even after adjustment for confounding variables. At the end of treatment or later, these correlations were lost. Evolution pattern of the HVR-1 quasispecies indicated a strong selective pressure in sustained responders, with complete substitution of pre-existing quasispecies, while minor changes occured in non responders. In relapsers both patterns were present at a similar rate. In conclusion, this study shows that HVR-1 heterogeneity may be involved in the early response to combined IFN-RBV therapy. The loss of correlation between viral heterogeneity and therapy outcome at 6 months of therapy, or later, suggests that other factors may play a role in maintaining sustained response to treatment.

Solitary plasmacytoma of bone and extramedullary plasmacytoma: two different nosological entities?

BACKGROUND: The relationship between solitary plasmacytoma and multiple myeloma is still unclear, but they can be distinguished by their different clinical course. Indicators of disease activity and extension, and of a possible evolution to multiple myeloma, have not been identified as yet. METHODS: Two cases of solitary plasmacytoma are described: one of the mandible and one extramedullary plasmacytoma (EMP) of the rhinopharynx. Pathologic data included immunohistochemical staining for heavy and light Ig chains, and for the proliferating cell nuclear antigen (PCNA). Analysis of the peripheral immunological status and serum parameters (beta 2 microglobulin, thymidine kinase, IL-2, IL-6 and soluble IL-2 receptor) was performed and correlation was made with the clinical status. Flow cytometry analysis of nuclear DNA content and S-phase cell fraction were also studied in both neoplasms. RESULTS: Solitary plasmacytoma of bone (SPB) showed important basal immunologic alterations and a marked increase in all serum parameters considered with respect to EMP. Ploidy analysis demonstrated an almost complete aneuploidy cell population for the SPB patient (80%), whereas in the EMP patient only 2% of the cells were aneuploid. The S-phase cells were 16% and 4%, respectively. PCNA index was 60% in SPB and 10% in EMP. CONCLUSIONS: Solitary plasmacytoma of the bone appeared to be a more aggressive form of plasmacellular neoplasia, distinct from EMP and similar to multiple myeloma. The study of serum parameters, together with analysis of PCNA, ploidy and S-phase fraction, can aid in better understanding disease activity, and in the choice of more adequate treatment. Moreover, serial analysis of some serum factors might be useful markers for monitoring the disease.