Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

Abstract

Interferon (IFN) was the first cytokine discovered 50 years ago, with a wide range of biological properties, including immunomodulatory, proapoptotic and antiangiogenic activities, that rapidly raised interest in its therapeutic use in malignancies. IFN-receptor characterization was also pivotal in the discovery of the JAK/STAT signaling pathway. Among the large IFN family, mainly one of the type I IFN, IFN-a2, is used in therapy. Many clinical trials have shown remarkable efficacy of IFN-a in bcr-abl-negative myeloproliferative neoplasms (MPNs), especially polycythemia vera (PV), and essential thrombocythemia (ET). IFN-a induces about 80% of hematological responses in those diseases and is able to reduce splenomegaly, as well as relieve pruritus and other constitutional symptoms. Yet its use was limited by toxicity, leading to early treatment discontinuation in about 20% of the patients. However, its lack of leukemogenic potential and its possible use during pregnancy have already made IFN-a the drug of choice for younger MPN patients. In addition, several studies have shown a probably selective effect of IFN-a on PV and ET clones, as shown by cytogenetic remissions, reversions to polyclonal hematopoiesis, and more recently by induction of JAK2V617F complete molecular remissions in PV which may widen the indications of IFN-a in JAK2-mutated MPN.

Recombinant interferon alpha (rIFNα-2b) may retard progression of early primary myelofibrosis

“…The median spleen sizes in centimeters below the left costal margin were 7.0 cm (range 0.0-24.0 cm) before treatment, and 0 cm (range 0.0-20.0 cm) at last follow-up (Table 1). Our results are thus in sharp contrast with those reported in the literature by Kiladjian et al 1 Bone marrow follow-up studies were possible in nine of the 13 patients, and were carried out a median of 2.3 years after the start of the rIFNa-2b therapy (range 1.2-5.0 years). The median duration of interferon treatment was 3.0 years (range 0.17-13.4 years).…”

“…The use of interferon is based on its effects on megakaryopoiesis, which include decreasing megakaryocyte density and size, 2 inhibiting thrombopoietin-induced signaling, 3 suppressing the expression of transcription factors 4 and reducing levels of platelet-derived growth factor, 5 all of which play a major role in the pathogenesis of myelofibrosis. 1 The diagnosis of PM was established clinically, hematologically and by bone-marrow trephine biopsy, consistent with published criteria. [4][5][6] Pretreatment evaluation included history, physical examination, complete blood cell count and differential CD34 count, BCR-ABL and JAK2 V617F allele burden determinations, serum chemistries and thyroid function tests.…”

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

“…It is now well established that IFN-a can control erythrocytosis or thrombocytosis in the majority patients with PV or ET (usual dose is 3 million units SC three times-a-week) [118]. A similar degree of benefit is appreciated in terms of reduction in spleen size or relief from pruritus.…”

PEG‐IFN‐α‐2a therapy in patients with myelofibrosis

“…Since 1987, several studies have suggested that interferons (alpha or beta that are either pegylated or not) may be beneficial in the treatment of myelofibrosis (Parmeggiani et al, 1987;Kiladjian et al, 2008a). Given the efficacy of pegylated interferon a-2a (Peg-IFN a-2a) on biological and molecular parameters in polycythemia vera (PV) patients (Kiladjian et al, 2008b), we undertook a multicentre retrospective study in order to evaluate the impact of this treatment on the clinical and biological parameters inherent to myelofibrosis.…”