FCM significantly improves the sensitivity of CC for the identification of leptomeningeal disease in aggressive B-NHL at higher risk of CNS disease, particularly in paucicellular samples.

The management of patients with inhibitors is an important challenge in haemophilia care. The lack of randomized controlled trials means that clinical decisions are generally based on subjective opinions, and purchasers' attention is likely to focus on the costs of treatment. In order to assess the current management of inhibitor patients and use of immune tolerance induction therapy (ITI) in Europe, we performed a survey within a European network of 21 comprehensive care centres from 14 countries (the European Haemophilia Therapy Standardisation Board). The survey identified a total of 381 patients with inhibitors attending the centres, 211 (55.4%) of whom had never been exposed to ITI. Between 1998 and 2003, the centres performed 233 procedures and 114 (48.9%) were successful. The survey demonstrated that dosing, which is the time to start and stop the ITI, the type of concentrate to use and the definition of success varied among the centres. Well-designed trials are warranted to guide decision-making, but in the absence of these studies we have developed consensus guidance for the management of inhibitor patients based on current clinical practice, as identified by the survey, and review of the literature.

Veno-occlusive disease of the liver (VOD) is an important complication in hematological transplantation. The aim of this study is to analyze the risk factors for VOD and other forms of liver toxicity in a cohort of 180 peripheral stem cell transplants performed in our Center. We find that elevated pretransplant levels of serum ferritin are the most important risk marker for VOD. We believe that ferritin reflects damage induced by oxygen radicals resulting from iron-mediated catalysis. We also discuss different risk factors for VOD and other forms of liver toxicity, suggesting diferent pathogenic mechanisms.

Nowadays, the elective treatment for children with haemophilia is prophylaxis. There is a common consensus that this modality of therapeutic approach is not associated with a higher risk of inhibitor development. We analysed the inhibitor incidence in 50 haemophiliac children and its relationship with mutations, type of clotting factor used and treatment modality. There was a significant correlation between receiving on-demand treatment and an increased incidence of inhibitors, independently of mutations or factor used. We advise putting haemophiliac children under prophylactic treatment as soon as possible, especially if they have mutations associated with high risk of inhibitor development, as prophylaxis is negatively associated with the development of inhibitors.

We report our clinical experience with central venous catheters (CVCs) in 15 patients with haemophilia who, in total, had 34 catheters inserted. Eighteen devices were Hickman, six were Port-A-Cath and 10 were nontunnelled catheters (one Quinton, seven antecubital, one jugular and one subclavian vein access). All patients had factor VIII/IX inhibitors at the time of insertion. The mean age at operation was 8.8 years (range 16 months-39 years). Eight of the 15 patients (26/34 implanted catheters, 76%) presented some kind of complication. Pericatheter bleeding during the postoperative period affected a total of seven CVCs (7/34, 20%) in six patients, which required substitutive treatment for several days. Infection was reported in 15 of the CVCs (15/34, 44%), and four of these (4/15, 26%) had more than one episode, with a mean of 1.4 infection episodes per catheter (21/15). The infection rate was 0.2 infections per 1000 patient days or 0.1 per 1000 catheter days. Despite the usefulness of CVCs in haemophilic patients, the high incidence of complications requires careful assessment of the type of device as well as continuous surveillance.

The ultimate goal of treatment for patients with inhibitory antibodies should be to permanently eradicate the inhibitor by immune tolerance induction therapy (ITI). However, ITI procedures fail in a substantial number of patients and in many countries ITI is not even offered owing to its high cost. How patients with inhibitors are managed in different European countries is evaluated with a special focus on the use of by-passing agents, i.e. recombinant FVIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC), as well as the type of monitoring performed. Investigators from 22 large haemophilia centres participating within the network of the European Haemophilia Therapy Standardisation Board (EHTSB) were asked to complete a questionnaire. rFVIIa was routinely used in all centres for both children and adults at dosages ranging from 90 to 250 mug kg(-1) at an interval of 2-4 h. aPCC was used in 85% of the centres in adults and in 25% of the centres in children with haemophilia A at dosages of 50-100 IU kg(-1) every 6-12 h. The corresponding figures for children and adults with haemophilia B were 40% and 15% of the centres, respectively. Higher dosages of both agents were considered in the case of life-threatening bleeds. General recommendations were developed, based on the information provided by the survey. The results clearly indicate the need for well-designed comparative studies to optimize the use of by-passing agents.

The presence of occult CNS involvement at diagnosis in patients with NHL at high risk of CNS disease is associated with a higher probability of CNS relapse.

We have studied the regulation of adrenal function in male rats treated neonatally with monosodium glutamate (MSG) and in littermate controls. When 6–7 months old, MSG-treated rats presented reduced body, adrenal and pituitary weight, obesity, atrophy of the optic nerve and damage of the arcuate nuclei (ARN) of the hypothalamus. MSG-treated rats showed increased serum corticosterone (CORT) levels under resting conditions; after ether stress the increase in serum CORT was greater in MSG animals when compared to littermate controls. Plasma ACTH followed the same trend although it reached significance after ether stress only. Both circulating CORT and ACTH were normally suppressed by dexamethasone (DEX) administration. Levels of corticosteroid binding globulin were also increased, whereas daily circadian rhythm of serum CORT was blunted. We also determined cytosolic receptors in areas suggested to participate in the negative feedback of glucocorticoids at the central level. Binding of (³H)-DEX in MSG rats was similar to controls in hippocampus, whole hypothalamus and anterior pituitary, but a significant reduction (≈ 50%) was obtained after microdissection in the area normally occupied by the ARN, without changes in the ventromedial nuclei of the hypothalamus. These results suggest that the ARN may be involved in the regulation of the pituitary-adrenal axis, although the abnormalities observed in the MSG syndrome partially differ from those in rats with hippocampal damage, previously studied in our laboratory.