Alfa-interferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone

Abstract

The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemia (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 neoplastic 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 hematological remission (CHR) and one achieved partial hematological remission. Megakaryocyte concentration was reduced in six cases. The spleen,which was enlarged in four patients, decreased in size in two patients. Seven of eight patients who were symptomatic at diagnosis obtained resolution of symptoms. In order to obtain indications about the structural modifications induced by alfa-IFN in ET megakaryocytes (Mks), Fourier-transform infra-red microspectroscopy analysis performed on 10 single Mks of each patient, was done in seven of 11 patients; the analysis showed a reduction of A 1 /A 2 ratios (A 1 integrated area of the band at 1080 cm −1 due to the nucleic acids absorption; A 2 integrated area of the band at 1540 cm −1 due to proteic components absorption) 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 observe 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 demonstration of the depth of the effect of alfa-IFN on the neoplastic clone. The results of clonality studies showed the persistence of clonal hematopoiesis. Whether higher alfa-IFN dose and/or more prolonged alfa-IFN therapy may allow a restoration of polyclonal hematopoiesis remains to be determined and should be explored in future clinical trials.

The Optimal Management of Polycythaemia Vera

“…However, in some studies, despite normalization of peripheral blood counts, erythropoietin‐independent colony formation persisted, histamine levels were not reduced and bone marrow hyperplasia was sustained (Silver, 1997), suggesting that the malignant clone was not eradicated. The experience in essential thrombocytosis has been similar (Sacchi et al , 1998). It should also be emphasized that cytogenetic conversion may not be synonymous with suppression or eradication of the malignant clone, as the cytogenetic abnormalities in polycythaemia vera are not specific for the disease, not commonly present at onset (Swolin et al , 1988) and not necessarily representative of all clones in the bone marrow (Kanfer et al , 1992; Asimakopoulos et al , 1996).…”

Recent Progress in Interferon Therapy for Myeloid Malignancies

“…Treatment of ET typically involves combinations of aspirin, ticlopidine, hydroxyurea and anagrelide to reduce platelet number and manage clotting (115,116). IFN therapy in ET is also effective for reducing platelet numbers while also reducing the risk of thrombotic complications (107,117) but does not appear to restore polyclonal haematopoiesis (118). Studies that will directly compare pegylated IFN-a2a to hydroxyurea in ET and PV are currently ongoing (110).…”

Essential thrombocythaemia

“…Fever and flu-like symptoms are experienced by most patients upon initiation of therapy; these and other side-effects, particularly depressive disorders, necessitate drug cessation in up to 20% of patients.> Although there have been previous reports of (X-IFN therapy inducing sustained remissions off treatment in ET, a sustained effect on the neoplastic clone has not been demonstrated in more recent studies. 16,24 Alternative agents: Generally, alkylating agents and 32p are avoided because of their leukaemogenic potential. However, 32p is an appropriate and effective therapy for elderly patients if compliance or daily drug administration is inconvenient or ineffective.…”