ALPHA-INTERFERON IN THE TREATMENT OF ESSENTIAL THROMBOCYTHEMIA - CLINICAL-RESULTS AND EVALUATION OF ITS BIOLOGICAL EFFECTS ON THE HEMATOPOIETIC NEOPLASTIC CLONE

The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemi a (ET) patients has been reported by several authors. The aim of this study is to assess the magnitude of the effect of alfa-IFN on the neop lastic clone. As of December 1993, 11 ET patients received alfa-IFN at a dose of 3-6 MU/s.c./day for 6 months. Ten of 11 obtained complete h ematological remission (CHR) and one achieved partial hematological re mission. Megakaryocyte concentration was reduced in six cases. The spl een,which was enlarged in four patients, decreased in size in two pati ents. Seven of eight patients who were symptomatic at diagnosis obtain ed resolution of symptoms. In order to obtain indications about the st ructural modifications induced by alfa-IFN in ET megakaryocytes ([Wks) , Fourier-transform infra-red microspectroscopy analysis performed on 10 single Mks of each patient, was done in seven of 11 patients; the a nalysis showed a reduction of A(1)/A(2) ratios (A(1) integrated area o f the band at 1080 cm(-1) due to the nucleic acids absorption; A(2) in tegrated area of the band at 1540 cm(-1) due to proteic components abs orption) in five cases, and in three of these five patients A(1)/A(2) ratios achieved normal values. After alfa-IFN treatment we did not obs erve any change in the methylation pattern of DNA from the granulocyte fraction. Our results confirm the efficacy of alfa-IFN in ET patients , and the decrease of A(1)/A(2) ratios in several patients is a demons tration of the depth of the effect of alfa-IFN on the neoplastic clone . The results of clonality studies showed the persistence of clonal he matopoiesis. Whether higher alfa-IFN dose and/or more prolonged alfa-I FN therapy may allow a restoration of polyclonal hematopoiesis remains to be determined and should be explored in future clinical trials.