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.
Toxicity related to autologous PBSC infusion is well known and traditionally attributed to the presence of DMSO as cryoprotectant. But despite DMSO depletion, adverse events continue appearing. We have conducted a retrospective study to determine the incidence of adverse events related to the PBSC infusion in a large series of 144 patients. Adverse effects were observed in 67.36% of patients, although most of them were of grade 1 or 2. The adverse events most frequently reported were allergic reactions, followed by general, gastrointestinal and respiratory symptoms. In the univariate analysis, age (P ¼ 0.01), the volume infused (P ¼ 0.005), the amount of DMSO (P ¼ 0.008), the total nucleated cells (P ¼ 0.002), the total number of granulocytes (P ¼ 0.000001) and clumping (P ¼ 0.000001) were associated with the occurrence of adverse events. In the multivariate analysis, two protective factors, age (P ¼ 0.05) and sex (P ¼ 0.004), and two risk factors, the number of granulocytes, with a relative risk of 1.18 (95% confidence interval, 1.06-1.31) (P ¼ 0.002), and clumping, with an relative risk of 1.94 (95% confidence interval, 1.15-3.29) (P ¼ 0.013), were identified. The best cutoff point for the prediction of the occurrence of adverse events, with a sensitivity of 47% and specificity of 89%, was 6.065 Â 10 9 granulocytes.
Donors' age, with a threshold of 38 years or more, and the rHuG-CSF schedule are the factors that significantly affected CD34+ cell mobilization and collection in healthy donors.
Summary:In order to assess the potential clinical benefit of filgrastim (G-CSF) after peripheral blood stem cell (PBSC) autotransplantation a randomized study was begun in our center in July 1997: 62 patients were involved (30 received filgrastim after PBSC infusion and 32, the control group, received no cytokines). All were adults (median 40 years, range 18-65). Patients with one of three different pathologies were recruited: 28 had advanced breast carcinoma, 23 had lymphomas (12 Hodgkin's disease and 11 non-Hodgkin's lymphoma) and 11 had de novo AML. All of them were transplanted using myeloablative chemotherapy conditioning regimens. G-CSF was administered subcutaneously from day +5 in the treated group at a dose of 5 g/kg body weight/day. The numbers of CD34 + and mononuclear (MNC) cells infused were similar in each group. Only minor differences regarding the use of G-CSF could be inferred from the analysis of the data. Faster granulocyte engraftment was evident in the treated group (mean of 10 vs 12 days to achieve Ͼ0.5 × 10 9 /l granulocytes, P = 0.0008), without differences in incidence and severity of infections, days of fever or duration of antibiotic treatment between groups. There was slightly slower platelet engraftment (mean of 15 days in the group with G-CSF vs 12 days in the other group to achieve Ͼ20 × 10 9 /l platelets, P = NS) in this series, but there were no differences in incidence and severity of haemorrhage or platelet transfusion support. Considering the economical costs, the median expenditure per inpatient stay was Eur5961 (range Eur4386-Eur17186) in the G-CSF group compared with Eur5751 (range Eur3676-Eur15640) in the control group (P = 0.47). From our data it could be concluded that for adult patients transplanted with PBSC there is no clear beneficial impact of post-infusion G-CSF administration.
The administration of rHuG-CSF to donors <18 years old leads to CD34+ cell mobilization in a pattern similar to that observed in adults. Greater age was associated with a more frequent requirement for more than one apheresis to achieve a similar number of CD34+ cells.
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