The aim of this study was to determine whether the burden of JAK2 V617F allele correlated with major clinical outcomes in patients with polycythemia vera (PV). To this end, we determined JAK2 mutant allele levels in granulocytes of 173 PV patients at diagnosis. The mean (7s.d.) mutant allele burden was 52% (729); 32 patients (18%) had greater than 75% mutant allele. The burden of JAK2 V617F allele correlated with measurements of stimulated erythropoiesis (higher hematocrit, lower mean cell volume, serum ferritin and erythropoietin levels) and myelopoiesis (higher white cell count, neutrophil count and serum lactate dehydrogenase) and with markers of neutrophil activation (elevated leukocyte alkaline phosphatase and PRV-1 expression). As compared to those with less than 25% mutant allele, patients harboring greater than 75% JAK2 V617F allele were at higher relative risk (RR) of presenting larger spleen (RR 4.7; Po0.001) or suffering from pruritus (RR 3.1; Po0.001). In these patients, the risk of requiring chemotherapy (RR 1.8; P ¼ 0.001) or developing major cardiovascular events (RR 7.1; P ¼ 0.003) during follow up were significantly increased. We conclude that a burden of JAK2 V617F allele greater than 75% at diagnosis points to PV patients with high-risk disease.

Summary.To determine whether patients with a HLAidentical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention-totreat principles was performed within the framework of the EORTC-GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT), the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: five in resistant disease, 14 during relapse and 19 in CR2. ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six (2%) patients during relapse and in 38 (10%) patients during CR2. The disease-free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P ¼ 0·01, RR 0·78, 95% confidence interval 0·63-0·96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P ¼ 0·24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.

The pharmacokinetics of Factor VIII was evaluated by mathematical modeling in a large-scale study in 62 haemophilia-A subjects, in whom 137 plasma Factor VIII-time curves were measured during single dose (n = 87) and repeated-dose (n = 47) treatments for prophylaxis or minor bleeding episodes. The pharmacokinetic parameters [mean (SD)] estimated from single-dose curves were: clearance 3.85 ml.h-1.kg-1, volume of distribution 58.2 ml.kg-1, mean residence time 15.9 h. Parameters calculated from repeated-dose curves were: clearance 3.93 ml.h-1.kg-1, volume of distribution 61.8 ml.kg-1, and half-life 12.2 h. In patients with mild haemophilia, pharmaco-statistical analysis revealed that the endogenous synthesis of Factor VIII was constant and was not influenced by the administration of exogenous Factor VIII. The coefficient of variation for intra-individual variability of Factor VIII kinetics (estimated according to the Standard Two-Stage method) was 20.7% in single-dose curves and 23.2% in repeated-dose curves.

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A group of 27 first infused haemophiliacs was studied for association between heat-treated clotting factor concentrates and transmission of human parvovirus B19. The prevalence rate of B19 antibody, detected by the Immunoelectroosmophoresis (IEOP) reaction, was 55.5% in this group of first infused subjects, significantly higher than the 29.3% of the control group of 58 healthy blood donors but lower than the 93.3% of antibody positive subjects in a group of 30 haemophiliacs multitreated with unheated products. Five of 17 B19 antibody negative patients produced human parvovirus IgM, detectable by radioimmunoassay, after the first treatment with heated concentrates; two of them developed viraemia 6 and 10 days, respectively, after the first infusion dose. These results lead to the conclusion that human parvovirus is transmissible by blood derivatives even when they have been exposed to steam- or dry-heat treatment.