Long term molecular responses in a cohort of Danish patients with essential thrombocythemia, polycythemia vera and myelofibrosis treated with recombinant interferon alpha.

Within recent years data has accumulated demonstrating the efficacy of recombinant interferon alpha2 (rIFN-alpha2) in the treatment of chronic myeloproliferative neoplasms (MPNs). We report on clinical and molecular data in the largest cohort of JAK2 V617F mutant MPN Danish patients (n=102) being treated long-term with rIFN-alpha2 (rIFN-alpha2a and rIFN-alpha2b in a non-clinical trial setting. The median follow-up was 42 months. We substantiate the capacity of rIFN-alpha2 to induce complete hematologic remissions (ET 95%, PV 68%) and molecular response. In total 76 patients (74.5%) had a decline in JAK2 V617F allele burden with a median reduction from baseline of 59% (95% c.i. 50-73%, range 3-99%). A decline in JAK2 V617F allele burden was recorded in both ET (median 24-10% (95% c.i.: 8-16%), and PV (median 59-35% (95% c.i.: 17-33%). Patients with the lowest pre-treatment JAK2 V617F allele burdens tend to achieve the most favourable responses on long term treatment with rIFN-alpha2. Eleven patients (10%) had deep molecular remissions with ≤ 2% JAK2 V617F mutant DNA. Finally, long term treatment with rIFN-alpha2 was associated with a very low thrombosis rate. Our observations are supportive of the concept of early up-front treatment with rIFN-alpha2.

Smoking, low density lipoprotein cholesterol, fibrinogen and myocardial infarction before 41 years of age: a Danish case-control study.

BACKGROUND: Of major coronary risk factors, smoking and total cholesterol were significant in a previous Danish case-control study of myocardial infarction at a young age. OBJECTIVE: To determine whether smoking was an important coronary risk factor in the context of new and major anthropometric and biochemical risk factors for myocardial infarction in individuals less than 41 years of age. METHODS: A prevalence hospital-based matched case-control study of young individuals. We selected 22 Caucasian cases and 24 Caucasian controls without coronary heart disease matching for age and gender and studied a series of major coronary risk factors and newer anthropometric and biochemical variables. RESULTS: In conditional univariate logistic regression analyses, the following factors were significantly associated with the coronary risk: family history, social class, smoking, intraabdominal adipose tissue area as percentage of total abdominal adipose tissue area on a CT scan, glycosylated haemoglobin level, systolic blood pressure, total cholesterol, low density lipoprotein (LDL) cholesterol, homocysteine, and fibrinogen levels (P < 0.05). However, in multiple conditional logistic regression analyses, only smoking, LDL cholesterol, and fibrinogen levels remained significant. Ten cases (46%) and none of the 24 controls were smokers with a LDL cholesterol level 4.5 mmol/l and a fibrinogen level 3.7 g/l (P = 0.0003, Fisher's exact test). CONCLUSION: Out of a series of major and newer coronary risk factors in young Western Caucasians, smoking, and levels of LDL cholesterol, and fibrinogen were independent significant coronary risk factors. The findings need to be validated in prospective studies.