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Inadequate resistance to oxidative stress has been implicated in several diseases of premature children. Antioxidative defences at the membrane level can be studied by measuring haemolysis induced through exposure of erythrocytes to the free radical generator AAPH (2,2'-azobis (2-amidinopropane)dihydrochloride). We developed a micromodification of this haemolysis test requiring only 15 μl of erythrocytes derived from capillary blood samples. The time needed for 50% haemolysis (T50%) was used to characterize radical resistance of erythrocytes. T50% results in adult samples were highly reproducible. T50% values in healthy term infants on the first 2 d of life were lower than in adults (p<0.001), but increased to the same level thereafter. A correlation was found between T50% values and plasma tocopherol levels as determined in plasma of each of the capillary blood samples (p<0.001). On the first day of life T50% results in preterm infants (n=20) were higher than in term infants (p<0.001). It was easy to monitor T50% results and plasma tocopherol levels in preterm infants that were not at all burdened by the sampling method, almost daily over several weeks. The micromodification presented simplifies monitoring of antioxidative defences in sick preterm infants. [ABSTRACT FROM AUTHOR]

Inadequate resistance to oxidative stress has been implicated in several diseases of premature children. Antioxidative defences at the membrane level can be studied by measuring haemolysis induced through exposure of erythrocytes to the free radical generator AAPH (2,2'-azobis (2-amidinopropane)dihydrochloride). We developed a micromodification of this haemolysis test requiring only 15 microl of erythrocytes derived from capillary blood samples. The time needed for 50% haemolysis (T50%) was used to characterize radical resistance of erythrocytes. T50% results in adult samples were highly reproducible. T50% values in healthy term infants on the first 2 d of life were lower than in adults (p < 0.001), but increased to the same level thereafter. A correlation was found between T50% values and plasma tocopherol levels as determined in plasma of each of the capillary blood samples (p < 0.001). On the first day of life T50% results in preterm infants (n = 20) were higher than in term infants (p < 0.001). It was easy to monitor T50% results and plasma tocopherol levels in preterm infants that were not at all burdened by the sampling method, almost daily over several weeks. The micromodification presented simplifies monitoring of antioxidative defences in sick preterm infants. [ABSTRACT FROM AUTHOR]

A five-agent GVHD prophylaxis programme consisting of cyclosporin A, methotrexate, anti-thymocyte-globulin, pentaglobin and metronidazol was given to 48 recipients of unrelated donor marrow with chronic myelogenous leukemia, acute leukemia, myelodysplastic syndromes, and familiar lymphocytic hemophagocytosis of an average age of 33.5 (0.6–56) years. GVHD grades II–IV occurred in 18 patients (39%) and grades III–IV in five patients (11%). Chronic GVHD developed in nine patients (23%), three limited and six extensive. Fifteen patients died. Clinical relapse was detected in eight patients. Four patients died as a consequence of the underlying disease and subsequent treatment, 11 patients died of transplant-related causes. After a median follow-up of 19 months, the overall and disease-free survival are 67% and 62%, respectively. Survival by age is as follows: 0–19 years: 12/13 patients; 20–39 years: 14/25 patients; 40–59 years: 7/10 patients. The five-agent GVHD prophylaxis regimen is effective. Matched-unrelated donor transplants can be carried out safely in patients younger than 50 years of age. The results in patients younger than 20 years of age should encourage matched-unrelated donor transplants at earlier stages of the disease. [ABSTRACT FROM AUTHOR]

Infections are a major cause of morbidity and mortality in patients undergoing high-dose therapy and subsequent autologous or allogeneic haemopoietic stem cell transplantation, despite the change from topical to systemic anti-infection prophylaxis and the introduction of growth factors and new antimicrobial drugs. We report our single centre experience with data from 409 patients treated at our unit from its opening in 1990 until May 1997. Three hundred and seventy-eight patients were transplanted for the first time, 12 patients were retransplanted or boosted and 19 patients were readmitted for miscellaneous reasons. 245 patients were allografted and 157 autografted. Antimicrobial prophylaxis was mainly quinolones, fluconazole plus amphotericin-B orally, aciclovir, and TMP/SMX or pentamidine. Three hundred and nineteen (78%) developed fever of significantly longer duration in the allogeneic setting with anti-CMV seropositivity. The most frequent infection was fever of unknown origin (50.6%), followed by septicaemia (12.5%) and pneumonia (11.0%). Pathogens isolated in 24.6% of the infections were mostly gram- positive bacteria (57.9%), followed by non-fermenting rods (11.2%), Aspergillus spp. and Candida spp. (10.3%, each). Cumulative response rate to antimicrobial therapy was 66.9%. Infections were responsible for 62.5% (25/40) of deaths after transplantation. Predominant pathogens were Aspergillus spp. (11), Candida spp. (four), and Pseudomonas spp. (three). None of the patients died from gram-positive bacterial infection. The risk of dying from infection was 11.2% after allografting and 0.8% after autotransplantation. Infections remain a major risk for early death after allogeneic transplantation of haemopoietic stem cells. Infection with gram-negative bacteria can be prevented by quinolone prophylaxis. Predominant pathogens are Aspergillus spp. Candida spp. and nonfermenting rods. Systemic infection with these pathogens is associated with a poor prognosis.... [ABSTRACT FROM AUTHOR]

We investigated an intensified conditioning regimen including fractionated total body irradiation (12 Gy), etoposide (30–45 mg/kg) and cyclophosphamide (120 mg/kg), followed by autologous (n = 5), allo-related (n = 13) or allo-unrelated (n = 6) bone marrow (n = 22) or peripheral stem cell (n = 2) transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. One patient received busulfan (16 mg/kg) instead of TBI. Nineteen patients were transplanted in 1CR, two in 2CR, one in 1PR and two in relapse. Major toxicity was mucositis grade II according to the Bearman scale in all patients. The treatment-related mortality was 25%, mainly due to infection or GVHD after allogeneic transplantation. After a median follow-up of 45 months (range 2–93), nine patients (37.5%) remain alive in CR. Nine patients (37.5%) relapsed and eight (33.3%) of these subsequently died. After autologous transplantation, four of five patients (80%) relapsed and died. Late relapse was seen after allogeneic, as well as autologous transplantation, at 33 and 59 months, respectively. The Kaplan–Meier estimate of leukemia-free survival for all patients is 38% at 3 years (95% CI: 18–58%) and 35% at 5 years (95% CI: 15–55%). For allogeneic transplants in first CR (n = 15) the estimate of disease-free survival was 46% at 3 years (95% CI: 19–73%) and 34% at 5 years (95% CI: 17–51%). Patients aged below 30 years had a better estimated overall survival at 3 years (61% vs 11%, P < 0.001). the bcr-abl fusion transcript (p210 vs p190 vs p210/190) did not affect disease-free or overall survival. In our experience, an intensified conditioning regimen seems to improve the results of bone marrow transplantation in patients with Ph+ acute lymphoblastic leukemia. However, the high relapse rate warrants novel approaches to enhance anti-leukemic efficacy. [ABSTRACT FROM AUTHOR]