Mitoxantrone, etoposide and cytarabine following epigenetic priming with decitabine in adults with relapsed/refractory acute myeloid leukemia or other high-grade myeloid neoplasms: a phase 1/2 study.

DNA methyltransferase inhibitors sensitize leukemia cells to chemotherapeutics. We therefore conducted a phase 1/2 study of mitoxantrone, etoposide and cytarabine following 'priming' with 5-10 days of decitabine (dec/MEC) in 52 adults (median age 55 (range: 19-72) years) with relapsed/refractory acute myeloid leukemia (AML) or other high-grade myeloid neoplasms. During dose escalation in cohorts of 6-12 patients, all dose levels were well tolerated. As response rates appeared similar with 7 and 10 days of decitabine, a 7-day course was defined as the recommended phase 2 dose (RP2D). Among 46 patients treated at/above the RP2D, 10 (22%) achieved a complete remission (CR), 8 without measurable residual disease; five additional patients achieved CR with incomplete platelet recovery, for an overall response rate of 33%. Seven patients (15%) died within 28 days of treatment initiation. Infection/neutropenic fever, nausea and mucositis were the most common adverse events. While the CR rate compared favorably to a matched historic control population (observed/expected CR ratio=1.77), CR rate and survival were similar to two contemporary salvage regimens used at our institution (G-CLAC (granulocyte colony-stimulating factor (G-CSF); clofarabine; cytarabine) and G-CLAM (G-CSF; cladribine; cytarabine; mitoxantrone)). Thus, while meeting the prespecified efficacy goal, we found no evidence that dec/MEC is substantially better than other cytarabine-based regimens currently used for relapsed/refractory AML.

The influence of increased roof strength on belted and unbelted dummies in rollover and drop tests.

This report condenses and summarizes two related and previously published reports. These two reports analyzed the effect of added roof strength on both belted and unbelted dummies. The reports, which have been dubbed Malibu I and Malibu II, respectively, presented data from a total of 16 rollover crash tests and four test conditions in which vehicles were dropped on their roofs. To evaluate the effect of roof strength, half of all test vehicles were modified to incorporate rigid rollcages, the other half were production vehicles. To evaluate the effect of belt restraints, half of all tests incorporated restrained dummies, the other half were unrestrained. The data from these tests clearly demonstrated that increased roof strength provided no reduction in dummy neck loads for belted or unbelted dummies when they were located over the area of the roof that impacted the ground. The tests also demonstrated that the neck loads resulted from "diving" type impacts, where the head stops and the torso momentum loads the neck. Roof deformation never caused the dummy to be compressed between the roof and seat.