Ristocetin-induced platelet aggregation for monitoring of bleeding tendency in CLL treated with ibrutinib.

Bleeding because of impaired platelet function is a major side effect of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib. We quantitatively assessed ristocetin-induced platelet aggregation (RIPA) in 64 patients with chronic lymphocytic leukemia (CLL) under ibrutinib at 287 time points. Eighty-seven bleeding episodes in 39 patients were registered (85 Common Toxicity Criteria (CTC) grade 1 or 2, 2 CTC grade 3) during a median observation period of 10.9 months. At times of bleeding, RIPA values were significantly lower (14 vs 28 U; P<0.0001). RIPA was impaired in patients receiving concomitant antiplatelet therapy or anticoagulation (14 vs 25 U, P=0.005). A gradual decline of median RIPA values was observed with increasing bleeding severity. Importantly, no CTC grade 2 or 3 bleeding were observed with RIPA values of >36 U. Sequential monitoring indicated a decrease of RIPA values from a median of 17 to 9 U within 2 weeks after initiation of treatment as well as an increase above the critical threshold of 36 U within 7 days when ibrutinib was paused. Low RIPA values were similar during treatment with another BTK inhibitor, CC292. Quantitative assessment of platelet function is a practical tool to monitor bleeding tendency under BTK-inhibitor therapy.

Compatibility of plastics with cytotoxic drug solutions-comparison of polyethylene with other container materials.

In this study low density polyethylene (LDPE)-containers were compared to glass bottles and polyvinyl chloride (PVC) bags in view of adsorption effects with antineoplastic drugs. The infusion containers were supplemented with therapeutic doses of the nine common cytotoxic drugs carboplatin, carmustine, cytarabine, dacarbazine, fluorouracil, gemcitabine, melphalan, methotrexate and vinorelbine. 0.9% isotonic sodium chloride solution and 5% dextrose served as infusion solutions. The containers were stored at room temperature or at 4 degrees C, protected from light, for periods of up to 168 h. Turbidity, change of colour and visible crystallization were not observed. Samples were collected at different time intervals and drug contents were determined with high-performance liquid chromatography (HPLC). Preparations of carmustine showed no adsorption phenomena when stored in LDPE or in glass at 4 degrees C. At room temperature in LDPE, a slight decrease in concentration due to adsorption was monitored. However the drug loss in PVC bags was greater. Dacarbazine and melphalan showed decreases in concentration, which were independent on the type of container material. The remaining analyzed agents showed no drug loss at all. In conclusion, investigated drugs were stable in all three container types, with the best stability in glass bottles, followed by LDPE and PVC.