Title: The transcobalamin codon 259 polymorphism should be designated 776C>G, not 775G>C
Abstract: Efficacy and safety of long-term use of hydroxyurea in young patients with essential thrombocythemia and a high risk of thrombosisThe optimal treatment of young patients with essential thrombocythemia (ET) at high risk of thrombohemorrhagic complications is uncertain.Storen and Tefferi 1 recently reported on the long-term use of anagrelide, a platelet-lowering agent without myelosuppressive activity.In a population of 35 young ET patients (median age, 38 years; range, 17-48 years) followed for a median of 10.8 years (range, 7-15 years), rates of 20% for thrombosis, 20% for major bleeding, and 24% for anemia were observed.Hydroxyurea (HU) may be a more effective agent, because a significant reduction in the incidence of thrombotic complications was demonstrated in a randomized clinical trial including ET patients of all ages. 2 However, long-term exposure to this agent may increase the rate of leukemic transformation, and it is presently unknown how this benefit-risk ratio applies to younger patients.To address this issue, we examined a consecutive cohort of 25 ET patients aged younger than 50 years (median age, 42 years; range, 18-49 years) who started on HU therapy before January 1, 1997, and were previously untreated.Hydroxyurea was given for platelet count persistently higher than 1 500 ϫ 10 9 /L (12 cases; 48%) or the occurrence of a major vascular event, such as ischemic stroke (5 cases), myocardial infarction (3 cases), portal vein thrombosis (2 cases), peripheral arterial thrombosis (2 cases), or pulmonary embolism (1 case).Patients with thrombosis were given standard antithrombotic prophylaxis with aspirin (100 mg/d) if arterial, or warfarin to a target international normalized ratio of 2.5 if venous.No cytoreductive drugs other than HU were used.The median platelet count at the start of HU was 933 ϫ 10 9 /L (range, 426-3 200 ϫ 10 9 /L).The aim of therapy was to maintain platelet count less than 600 ϫ 10 9 /L, or less than 400 ϫ 10 9 /L in those patients who had thrombosis with platelet count between 400 and 600 ϫ 10 9 /L.Patients were checked every 3 months, or more frequently if indicated, and, at the last control, the target range of platelet counts was achieved in 20 patients (80%) (median, 450 ϫ 10 9 /L; range, 312-698 ϫ 10 9 /L).After 8 years median follow-up (range, 5-14 years), no patient had to withdraw the drug for intolerance or adverse effects.One case (4%) of transient ischemic attack but no major thrombosis or severe bleeding was recorded.Most important, no case of leukemic or neoplastic transformation or death occurred.This indirect comparison of long-term cohort studies suggests that HU is more effective than anagrelide in preventing thrombosis in the young, apparently without an increase in leukemic risk.We read with great interest the recent article by Miller et al 1 that examined the transcobalamin (TC) genetic polymorphism encoding proline or arginine at codon 259 in the TC gene (Pro259Arg) and its possible influence on indices of vitamin B12 status in healthy older adults.Based on serum levels of holoTC (the B12-TC complex) that were significantly higher in individuals who were 3749