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Available from: Gareth Gerrard
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ABSTRACT: Patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) often have constant minor side-effects which have a significant impact on their daily lives and on their adherence to prescribed medication. One possible strategy to minimize these side effects is to take advantage of low cross intolerance between different TKIs and to “proactively” change therapy. However it is not clear whether such a change can adversely affect response, induce resistance or indeed eliminate a given side effect. In this work we describe outcomes in 57 patients who after attaining complete cytogenetic response changed from imatinib to a second generation TKI solely due to persistent minor side effects. After one or more changes of therapy 46 of the 57 patients were entirely free of side effects and an additional 11 patients had nearly complete resolution of side effects resulting in total or almost complete absence of minor persistent side effects in all cases. Furthermore all patients improved their levels of molecular response and BCR-ABL1 kinase mutations were not detected in any patient after change of therapy. Proactively changing therapy on account of persistent minor side effects seems to be an effective and safe therapeutic option for CML patients.
Available from: Carolyn M Millar
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ABSTRACT: Haemophilia B, resulting from a deficiency of coagulation factor IX (FIX), is treated effectively by either recombinant (r) or plasma derived (pd) FIX concentrates although differences in pharmacokinetics are observed. FIX is activated in vivo by both FXIa and tissue factor (TF)-FVIIa, however conventional APTT-based assays assess only activation by FXIa.
To examine the differences between pd-FIX and r-FIX concentrates with respect to their thrombogenicity and activation.
FIX ELISA was used to quantify antigenic FIX. Calibrated automated thrombography (CAT) was performed to evaluate the effect of FIX on thrombin generation. FIXa was quantified by the cleavage of FIXa specific chromogenic substrate. FIX activation was studied in a purified system.
We found that r-FIX had ~1.6 fold greater specific activity than pdFIX. r-FIX generated a markedly higher thrombin peak compared to pd-FIX at equivalent antigen level when coagulation was initiated by TF, which was not seen in contact activation-triggered thrombin generation (TG). Interestingly, FIXa contained in r-FIX was 10 times higher than in pd concentrate. In a purified system, the amount of r-FIXa generated by FXIa in the first 10 minutes of activation was 1.37x that of pd-FIXa, whereas no difference was observed when triggered by TF/FVIIa.
Clear differences are observed between pd-FIX and r-FIX concentrates including the proportion of FIXa and the activation by FXIa. These may explain some of the discrepancies observed clinically and suggest that the APTT may not reflect their resultant in vivo properties. This article is protected by copyright. All rights reserved.
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