ALBERT

Description: Background α-interferon (IFN) is an effective treatment in polycythemia vera (PV) and essential thrombocythemia (ET). IFN can induce cytogenetic remissions in PV pts. However, 21–25 % of pts discontinue therapy due to side effects. Pegylated IFN has been suggested to have less side effects. Study design and patients: The Nordic MPD Study Group performed an open label phase II feasibility study of PegIntron® treatment in 42 MPD pts, 20 females and 22 males, median age 54 yr (range 29–77). Inclusion criteria were a platelet count of 〉 400x109/L in pts with symptoms or previous thrombosis (n=26) or 〉1000x109/L in asymptomatic pts without previous thrombosis (n=16). 22 pts had PV, 20 ET. 15 pts had previously received cytoreductive therapy; anagrelide (7), hydroxyurea (6), busulfan (1), P32 (1). Previous IFN therapy was not allowed. Median time from diagnosis to study start was 0.74 ys (0.01–30.2). Initial dose was 0.5 μg/kg once weekly. The treatment goal was a platelet count 〈 400x109/L in symptomatic patients and 〈 600 in asymptomatic patients (CR). If CR was not achieved within 12 weeks PegIntron was increased to 1 μg/kg/week. The dose was subsequently decreased to the lowest dose maintaining CR. Pts QoL was investigated using QLQ-C30 and HAD forms. Neutrophil PRV-1 mRNA expression was analyzed by quantitative RT-PCR prior to and after therapy. Results: Response to treatment was evaluated at 1,2,3,6,9 and 12 months. At 6 months, 29/42 pts (69 %) had achieved CR, after a median time of 83 days. The median dose at time of CR was 0.5 μg/kg/week. CR rate was not related to diagnosis or gender. 4/42 pts (10%) discontinued therapy early due to side effects, another 9 pts were taken off study at 6 months due to side effects or insufficient response. Only 4/14 responding PV pts required phlebotomy therapy, compared to 20/22 before PegIntron. 20/29 patients with CR at 6 months maintained CR at 12 months, whereas 9 pts had gone off study due to side effects. The mean platelet count was 875x109/L prior to therapy, and 512, 448, 362x109/L at 3,6 and 12 months in pts on therapy. No thrombotic or bleeding complications were observed. Side effects were common, the majority WHO grades I-II; fatigue (76 %), injection site reaction (64 %), flu-like symptoms (64 %), headache (56 %), muscle pain (51 %), depression (35 %), insomnia (24 %), hair loss (20 %). Mild elevations were noted of serum ALAT, creatinine and TSH in 19, 3 and 3 pts respectively. QoL data will be presented. Changes in PRV-1 expression were determined in 13 PRV-1 positive pts (9 PV, 4 ET) after 6 months and in 2 PV pts after 24 months. PRV-1 expression was normalized in 3/4 ET pts at 6 months and in 1/2 PV pts after 24 months treatment. Conclusion: We found PegIntron to be effective in reducing the platelet count in 29/42 pts (69 %) and 20 pts (48 %) remained in CR at 1 year. 22 pts (52 %) had discontinued therapy at 12 months, mainly due to side effects, a higher rate than in previous trials. Although analyzed in a small number of pts, reversal of PRV-1 positivity nonetheless suggests that PRV-1 quantification may be useful as a molecular marker of therapeutic efficacy.

Description: Background: Several strategies for managing patients with suspected PE have been validated. However, most of these strategies are complicated, involving multiple rounds of tests, and are thus, time consuming, costly and difficult to apply in clinical practice. Aiming to introduce a simple, fast and cost-effective strategy, we adopted a new diagnostic approach combining clinical probability assessment, D-Dimer and multi-slice spiral CT (MSSCT) scanning. Aims: The aim of this study was to assess the safety and efficacy of this management strategy by a prospective outcome study with 3-month follow-up. Methods: 495 consecutive patients referred to the Emergency Department at Østfold Hospital, Fredrikstad, Norway, for suspected PE, between Feb 2002 and Dec 2003, were considered for inclusion. 63 (12.7%) patients were excluded and the final cohort consisted of 432 patients. Patients were managed by serial non-invasive testing starting with D-Dimer test. Normal plasma D-Dimer (Liatest, latex agglutination assay, Stago-France, cut-off