One review analyzed the cumulative experience with IFN-alpha in 279 patients with PV from 16 studies.52 Overall responses were 50% for reduction of hematocrit to less than 0.45% without concomitant phlebotomies, 77% for reduction in spleen size and 75% for reduction of pruritus. In a review article, Silver updated his experience on the long term use (median: 13 years) of IFN-alpha in 55 patients with PV.53 Complete

responses, defined by phlebotomy free, hematocrit less than 45% and platelet number below 600 × 109/L, were reached in the great majority of cases after 1–2 years of treatment and the maintenance dose could be decreased in half of the patients. Noteworthy is the absence of thrombohemorrhagic events check details during this long follow-up. IFN-alpha has been also used in ET patients. The results of several cohort studies, reviewed in Lengfelder et al.54 indicate that reduction of platelet

count below 600 × 109/L can be obtained in about 90% of cases after about 3 months with an average dose of 3 million IU daily. IFN-alpha is not known to be teratogenic and does not cross the placenta. Thus, it has been used successfully throughout pregnancy in some ET patients PLX4720 with no adverse fetal or maternal outcome. The main problem with IFN-alpha therapy, apart from its costs and parental route of administration, is the incidence of side effects. Fever and flu-like symptoms are experienced by most patients not and usually require treatment with paracetamol. Signs of chronic IFN-alpha toxicity, such as weakness, myalgia, weight and hair loss, and severe depression, limit its long term use. Pegylated forms of IFN-alpha allow weekly administration, potentially improving compliance and possibly providing more effective therapy. A phase 2 study has shown that following pegylated interferon

alpha-2a therapy the malignant clone as quantitated by the percentage of the mutated allele JAK2V617F was reduced.55 More limited effects on JAK2 mutational status have been reported after therapy with pegylated interferon-alpha 2b in a small group of patients with PV and ET.56 Kiladjian et al.57 performed a prospective sequential quantitative evaluation of the percentage of mutated JAK2 allele (%V617F) by real-time polymerase chain reaction (PCR) in patients treated with pegylated interferon-alpha-2a. The %V617F was decreased in 26 (89.6%) of 29 treated patients from a mean of 45% to a mean of 22.5% after 12 months of treatment, with no evidence for a plateau being achieved. In two patients, JAK2V617F was no longer detectable after 12 months, such complete molecular response being observed in a total of 7 patients (24%) at time of last analysis after a median follow-up of 31 months. These impressive results have been confirmed by the M.D. Anderson Cancer Center investigators.