Summary:Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity after allogeneic bone marrow transplantation, but can be avoided by removing T lymphocytes from the donor bone marrow. However, T cell depletion increases the risk of graft rejection. In this study, two strategies are used to overcome rejection: (1) use of high doses of stem cells obtained from peripheral blood (PBSC), (2) admixture with a CD52 monoclonal antibody in order to deplete both donor and residual recipient lymphocytes. Two antibodies are compared: CAMPATH-1G (rat IgG2b) and its humanized equivalent CAMPATH-1H (human IgG1). A total of 187 consecutive patients at six centers received PBSC transplants from HLA-matched siblings between 1997 and 1999. A wide spectrum of diseases, both malignant and non-malignant, was included. The recovery of CD34 + cells after antibody treatment was close to 100%. The risk of acute GVHD (grade 2 to 4) was 11% in the CAMPATH-1G group and 4% in the CAMPATH-1H group (P = NS). The risk of chronic GVHD (any grade) was 11% in the CAMPATH-1G group and 24% in the CAMPATH-1H group (P = 0.03) but the risk of extensive chronic GVHD was only 2%. The overall risk of graft failure/rejection was 2%, not significantly different between the two antibodies. Antibody treatment was equally effective at concentrations between 10 g/ml and 120 g/ml and it made no significant difference to the outcome whether the patients received post-transplant immunosuppression or not (87% did not). Transplant-related mortality in this heterogenous group of patients (including high-risk and advanced disease) was 22% at 12 months. It is proposed that treatment of peripheral blood stem cells with CAMPATH-1H is a simple and effective method for depleting T cells which may be applicable to both autologous and allogeneic

One hundred therapeutic plasmaphereses were carried out at biweekly intervals in seven patients, without morbidity or mortality, using the IBM 2997 blood fraction separator. In standardised procedures, 1.5 times the calculated plasma volume was replaced with an electrolyte solution containing 4% salt-free human albumin. Anticoagulation was achieved using a whole venous blood to acid-citrate dextrose ratio of 11 to 1. Median flow rates, plasma collection, and procedure times were respectively 40 ml/minute, 20 ml/minute, and 3 hours. Haemoglobin and total white cell counts were not significantly affected by the procedures. In contrast, platelet count, fibrinogen, immunoglobulin levels, total haemolytic complement, as well as C3 and C4 fractions fell, and the prothrombin and partial thromboplastin times were lengthened by the exchanges. All these measurements had returned to normal within 24 hours, apart from the fibrinogen, which took between 48 and 72 hours, and the immunoglobulin level, which required 35 days to return to baseline. In a further patient, more detailed studies (n = 13) were carried out to characterise the behaviour of antithrombin III and factor VIII. Both levels were markedly reduced immediately following the procedure and, like fibrinogen, had returned to normal within 48 hours. These data indicate that in an isovolemic plasmapheresis there was a transient but rapidly reversible effect on all the factors studied, with fibrinogen level, antithrombin III, and factor VIII returning more slowly to normal than the others, and immunoglobulin levels responding the slowest. None of these changes was associated with clinically significant haemostatic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

BackgroundAbsolute iron deficiency, irrespective of aetiology, remains a major and worldwide cause of morbidity. After correction of the causative lesion, reconstitution of haemoglobin level and body iron stores is traditionally achieved with oral administration of ferrous salts. The latter have significant gastrointestinal tract side-effects that, in the short-term, may impair compliance. With protracted administration these products can cause lipid peroxidation which, in turn, may accelerate atherogenesis. An alternative formulation is an iron polymaltose complex where animal data supported a promoting effect of glycerophosphate. Setting and Trial Design This was a single-centre, open, randomised, multidose four treatment parallel group study. A standard dose of ferric polymaltose complex with two differing levels of glycerophosphate was compared with an equivalent amount of iron supplied as ferrous sulphate in anaemic volunteer blood donors. The endpoints were rate of haemoglobin rise and re-expansion of body iron stores reflected in blood ferritin concentration, as well as percentage saturation of transferrin. Secondary observations were changes in the proportion of hypochromic red cells during the course of treatment, erythropoietin levels and tolerability of the two formulations. Results Outcome in the rat model suggested that the utilisation of iron from polymaltose might be enhanced by glycerophosphate. However, in donors this difference was not evident and, accordingly, the data from the three polymaltose groups combined and compared to those receiving ferrous sulphate. The rate at which haemoglobin level improved, red cell indices returned to normal, and the number of hypochromic and microcytic red cells fell was not significantly different between the groups. Similarly the serum iron, percentage saturation of transferrin and red cell ferritin were comparable. In contrast the serum ferritin levels were higher for those receiving ferrous sulphate. Additionally, side-effects were significantly more frequently encountered with the latter preparation. Conclusion These data demonstrate that the addition of glycerophosphate, observed to be beneficial in rats, did not occur in humans. Secondly, in the blood donors, equivalent amounts of iron provided as the polymaltose, with or without glycerophosphate or ferrous sulphate, corrected haemoglobin concentration and morphologically abnormal erythropoiesis at comparable rates. Similarly iron stores are replenished to an equivalent extent as seen in the matching percentage saturation of transferrin and red cell ferritin levels. Interestingly, there is a discrepancy in the serum ferritin which is higher with the salt and this may reflect oxidative stress. Thirdly, corresponding efficacy can be achieved with better patient tolerance for the complex. Finally it is postulated that the iron polymaltose complex formulation more closely approximates the way in which enterocytes handle dietary iron and thus physiologic regulatory mechanisms would be expected to reciprocally...

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Echinocandin FK463 is of documented value in managing invasive candidiasis and aspergillosis. This is believed to be the first case of successful outcome with one of the angiotrophic zygomycetes.

Twelve consecutive adults with severe acute aplastic anaemia, not having a bone marrow transplantation option, were prospectively randomized to receive either cyclosporin A alone or an equivalent amount of this immunosuppressive agent in combination with antilymphocyte serum. The minimum follow-up is 36 months, with half the patients developing nephrotoxicity, which was easily reversible in all but one. No response could be attributed to either regimen. Cyclosporin A does not appear to have a place as primary form of treatment for adults with severe acute aplastic anaemia, either on its own or in combination with antilymphocyte serum.

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