Blood transfusions and adverse acute events: a retrospective study from 214 transfusion-dependent pediatric patients comparing transfused blood components by apheresis or by whole blood.

INTRODUCTION: Blood transfusion is a lifesaving procedure for patients affected by hematological diseases or hemorrhage risk. AIM: This retrospective study was aimed to evaluate clinical safety of pediatric transfusions by comparing the frequency of adverse events caused by apheretic blood components vs whole blood. METHODS: From 2011 to 2015, 214 patients (blood malignancy patients, n = 144 and thalassemic patients, n = 70) received 12 531 units of blood components. The adverse acute reactions occurred during patient hospitalization were reported to the Hemovigilance system and assessed by fitting a logistic mixed-effect model. RESULTS: A total of 33 (0.3%) adverse acute events occurred. Odds ratio (OR) of adverse events from apheresis vs whole blood transfusion adjusted by patient classification was not statistically significant (OR [95% CI], 0.75 [0.23-2.47]). CONCLUSION: Our findings showed no significant differences in the prevalence of adverse acute events between blood component collected by apheresis vs whole blood in our study center.

Farnesyl transferase inhibitors in clinical development.

Farnesyl transferase (FT) inhibitors block the main post-translational modification of the Ras protein, thus interfering with its localisation to the inner surface of the plasma membrane and subsequent activation of downstream effectors. Although initially developed as a strategy to target Ras in cancer, FT inhibitors have subsequently been acknowledged as acting by additional and more complex mechanisms that may extend beyond Ras, involving RhoB, centromere-binding proteins and probably other farnesylated proteins. SCH66336 (lonafarnib, Sarasar( trade mark ); Schering-Plough), a tricyclic orally active FT inhibitor, was the first of these compounds to undergo clinical development. Gastrointestinal tract toxicities and fatigue have qualified as dose-limiting toxicities in all Phase I/II studies. Evidence of clinical activity has been reported. Lonafarnib combination studies with both gemcitabine and paclitaxel have been carried out. No unexpected toxicities were observed in these Phase I studies, while encouraging clinical activity was observed mainly in pancreatic cancer and non-small cell lung cancer. Further combination studies are ongoing. R115777 (Zarnestra( trade mark ); Janssen Pharmaceutica) is another orally active FT competitive inhibitor in clinical development. Single-agent Phase I/II studies have shown that myelotoxicity and neurotoxicity are dose-limiting toxicities; intermittent schedule is probably better tolerated; antitumour activity is observed particularly in breast cancer and haematological malignancies. A number of combination studies with R115777 have been carried out. A recently completed, large Phase III trial comparing gemcitabine plus R115777 versus gemcitabine plus placebo in advanced pancreatic cancer has failed to demonstrate any survival benefit in the R115777 arm. BMS-214662 is the third FT inhibitor in clinical development. It has the main advantage of being cytotoxic in nature, rather than cytostatic, and potent in vivo antitumour activity has been reported. A major drawback for BMS-214662 is its severe gastrointestinal and liver toxicities, which prevent the achievement of adequate systemic exposures following the oral route. Alternative ways of interference with the ras oncogene pathway, in particular inhibition of ras downstream effectors, are discussed and early clinical data are presented.