IFN-beta induced biochemical and immunological modifications in hairy cell leukemia patients
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A M Liberati1, M Schippa, M G Portuesi
1Clinica Medica I, Università degli Studi di Perugia, Italy.
Background:
Although IFN-beta is 30-40% homologous with IFN-alpha, its intrinsic biological properties are not identical. Compared with IFN-alpha, IFN-beta exerts greater in vitro antiproliferative activity on many cell lines, stimulates peripheral blood stem cells of hairy-cell leukemia (HCL) patients to differentiate to erythroid burst forming cells, has higher specific type I IFN receptor affinity and modulates the expression of class II histocompatibility antigens. IFN-beta would, therefore, be expected to have a greater, or at least similar, antitumor activity as that of the various types of IFN-alpha.
Methods:
We have treated 12 patients affected by HCL with IFN-beta and have investigated the biological and immunological changes induced by such treatment.
Results:
A rise in beta 2-microglobulin and neopterin values throughout IFN-beta therapy was documented in most patients. An increase in NK activity was observed only in clinical responders whose CD57+/CD16+ cell ratio dropped below baseline. There was also a modulation in IFN-gamma synthesis that was dependent on baseline levels and in line with the clinical response. IFN-beta provoked a reduction in CD3+ and CD4+ cell subsets in patients with WBC greater than or equal to 10.0 x 10(9)/1 and greater than or equal to 50% circulating HCs, an expansion in absolute number of CD3+ and CD8+ cell fractions and a slight rise in the absolute values of CD2+ and CD4+ cell subpopulations in patients with WBC less than or equal to 5.0 x 10(9)/1 and less than or equal to 50% circulating HCs. There was no correlation between either the IFN-beta induced increase in beta 2-M or Np levels and clinical response. Most immunological parameters improved or normalized later during the course of IFN-beta treatment, when pathological-hematological signs of disease remission were already evident.
Conclusions:
The relevance of the IFN-beta induced changes as well as that of the IFN-alpha induced biological effects in the clinical control of HCL remain unclear.