Increased Discontinuation Rates of Anti-TNF Therapy in Elderly Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: There is paucity of data on safety and efficacy of anti-tumour necrosis factor [TNF] in elderly inflammatory bowel disease [IBD] patients. We aimed to compare the long-term treatment failure rates and safety of a first anti-TNF agent in IBD patients between different age groups [<40 years/40-59 years/≥60 years]. METHODS: IBD patients who started a first anti-TNF agent were identified through IBDREAM, a multicentre prospective IBD registry. Competing risk regression was used to study treatment failure, defined as time to drug discontinuation due to adverse events [AEs] or lack of effectiveness, with discontinuation due to remission as a competing risk. RESULTS: A total of 895 IBD patients were included; 546 started anti-TNF at age <40 [61.0%], 268 at age 40-59 [29.9%], and 81 at age ≥60 [9.1%]. Treatment failure rate was higher in the two older groups (subhazard rate [SHR] age ≥60 1.46, SHR age 40-59 1.21; p = 0.03). The SHR in the elderly [>60] was 1.52 for discontinuation due to AEs and 1.11 for lack of effectiveness. Concomitant thiopurine use was associated with a lower treatment failure rate (SHR 0.78, 95% confidence interval [CI] 0.62-0.98, p = 0.031). Serious adverse event [SAE] rate, as well as serious infection rate, were significantly higher in elderly IBD patients [61.2 versus 16.0 and 12.4 per 1000 patient-years, respectively] whereas the malignancy rate was low in all age groups. CONCLUSIONS: Elderly IBD patients starting a first anti-TNF agent showed higher treatment failure rates, but concomitant thiopurine use at baseline was associated with lower failure rates. Elderly IBD patients demonstrated higher rates of SAEs and serious infections.

The use of an insuflon device for the administration of G-CSF in pediatric cancer patients.

In pediatric oncology, granulocyte colony-stimulating factor (G-CSF) is applied with the aim of shortening neutropenic periods after chemotherapy and for mobilization of peripheral blood stem cells for apheresis procedures. G-CSF is administered, subcutaneously or intravenously, on a daily basis. An insuflon device for the administration of G-CSF was used in 29 patients for 93 G-CSF periods. Retrospective evaluation shows that this administration route is feasible, safe and preferred by young children rather than by teenagers with cancer.

Down modulation of fibronectin messenger RNA in metastasizing rat prostatic cancer cells revealed by differential hybridization analysis.

To identify genes whose expression is down modulated in the process of metastasis, gene expression was analyzed in cell lines derived from Dunning R-3327 rat prostatic tumor sublines. A complementary DNA (cDNA) library from the anaplastic nonmetastasizing subline AT-1 was used for a differential hybridization analysis, using probes derived from mRNAs of the AT-1 and the metastasizing MAT-LyLu subline. In this way 14 cDNA clones were isolated representing 6 differentially expressed genes. The expression levels in a panel of tumor sublines measured with these cDNA clones were tested for correlation with the anaplastic non-metastasizing phenotype. One cDNA clone, designated pSE-1, whose expression was high in all tested sublines with that phenotype, appeared to represent the gene for fibronectin. To further investigate the down modulation of this gene, we studied its expression in AT-2 (anaplastic, nonmetastasizing tumor) and lines derived therefrom that exhibited a high metastatic potential after transfection with the v-Ha-ras oncogene. In the genetically manipulated metastasizing tumor sublines, fibronectin mRNA levels were approximately 4- to 8-fold lowered compared to the nonmetastasizing parental AT-2 line.

Evaluation of the use of the Hemalog D in acute lymphoblastic leukaemia and disseminated non-Hodgkin's lymphoma in children.

In 79 children with acute lymphoblastic leukaemia and in 18 children with disseminated non-Hodgkin's lymphoma we investigated whether the automated cytochemical differential leucocyte count (Hemalog D) gives more accurate information than the manual differential count. We concluded that the manual count is superior to the Hemalog-D count with regard to the recognition of blast cells. Furthermore, Hemalog D is not helpful for the differentiation between acute lymphoblastic leukaemia and disseminated non-Hodgkin's lymphoma.