Receptor tyrosine kinases (RTK) play a significant role in the signal transduction of normal, and malignant hematopoietic cells. We have previously shown that Axl, a novel RTK, is mainly expressed in leukemias of myeloid origin, and that its expression may be associated with cells of monocytic origin. Since expression of certain RTKs in cancer may be associated with different biology and survival, we investigated whether the expression of Axl is associated with clinical characteristics and survival in acute myeloid leukemia (AML). RNA from 54 patients with AML treated in a cooperative group trial was analyzed in a retrospective and blinded manner using a semi-quantitative reverse transcriptase polymerase chain reaction-based assay with primers specific for the Axl gene. Axl expression was found in 19 out of the 54 cases (35%). Axl expression was not detected more frequently in patients of older age, specific FAB categories, or cases with extramedullary disease. However, there existed a correlation between Axl and bcl-2 expression levels. AML cells with high bcl-2 expression showed higher Axl expression (r = 0.32; P = 0.02), and furthermore, Axl transcript numbers were also higher in AML with high CD34 expression (n = 38, r = 0.42; P = 0.008). No significant difference between leukemias expressing and not expressing Axl was found with regard to complete remission rate. However, quantitative Axl expression was associated with worse progression-free and overall survival. Higher Axl levels had worse prognosis for progression-free (: 0.68, s.e.: 0.28, P = 0.015) and overall survival (: 0.61, s.e.: 0.31, P = 0.05) using multivariate Cox models adjusted for age, Auer rods and leukocyte counts. In conclusion, in this retrospective analysis, no difference with regard to clinical characteristics at diagnosis was found between AML patients whose leukemia cells show Axl expression vs patients whose cells are Axl negative. The association between Axl and bcl-2 and Axl and CD34 expression in de novo AML needs further investigation. Similarly, the negative impact of Axl levels on outcome should be confirmed in a larger cohort.
DC-based multi-epitope immunotherapy with repeated boosting in men with hormone-refractory prostate carcinoma is feasible and generates efficient cellular antitumor responses.
A nested polymerase chain reaction assay (nPCR) was used to investigate the potential of human parvovirus B19 DNA to persist in blood or bone marrow samples obtained either from blood donors or cadaveric bone donors or from patients presenting with clinical signs of parvovirus B19 infection. The presence of parvovirus B19 specific antibody in blood was tested by enzyme immunoassay (EIA). B19 virus genome was not detected in any blood sample of 115 blood donors, of whom 92 (80%) had anti-B19 IgG antibody only as an indication of past infection. In contrast; B19 virus DNA was detected in the bone marrow of 4 out of 45 bone donors. Each one of the serum samples available for 3 of these 4 individuals contained anti-B19 IgG antibody. Among 84 patients with clinical manifestations of parvovirus B19 infection, 17 (20%) had B19 virus DNA in bone marrow. Eight of the latter patients had anti-B19 IgG antibody in their blood but neither anti-B19 IgG nor B19 virus DNA. These data document the ability of parvovirus B19 DNA to persist in the bone marrow of asymptomatic individuals and patients with parvovirus B19 infection suspected on clinical grounds.
Among the well known transfusion-associated risks, the transmission of pathogenic viruses is regarded as one of the most serious. Over the past two decades, a series of overlapping safety procedures have been successively implemented to minimise this risk. It is now generally considered that the risk of transmitting viral infections via blood products is very low in developed countries.
The present study analyses the incidence of the key infectious diseases HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) between 1996 and 2003 from 99% of voluntary repeat blood donors visiting the blood transfusion service of the Swiss Red Cross. Furthermore the estimated risk of these viral markers was calculated. From 1996 to 2003 the incidence rate for HCV decreased continuously, whereas no significant decrease in the incidence rate of HIV and HBV was observed. From 2001 to 2003, the last calculated period, the residual risk was estimated to be 1 in 1 900 000 for HIV, 1 in 2 200 0000 for HCV and 1 in 115 000 for HBV, respectively. This agrees with international studies, which have been shown that the estimated residual risk for HBV between 1996 and 2003 is higher than that of HCV and HIV.
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