Ibrutinib for Relapsed / Refractory CLL: A UK and Ireland Analysis of Outcomes in 315 patients

In 2014, ibrutinib was made available for relapsed/refractory chronic lymphocytic leukaemia (CLL) patients. The UK CLL Forum collected data from UK/Ireland patients with a minimum of 1 year follow-up with pre-planned primary endpoints; the number of patients still on therapy at 1 year (Discontinuation Free Survival; DFS) and 1 year overall survival (OS). With a median 16 months follow-up, data on 315 patients demonstrated 1 year DFS of 73.7% and 1 year OS of 83.8%. Patients with better pre-treatment performance status (PS 0/1 vs 2+) had superior DFS (77.5% vs 61.3%;p14 days and had OS of 89.7%, while 26% of patients had dose reductions and 13% had temporary treatment breaks >14 days. We could not demonstrate a detrimental effect of dose reductions alone (1 year OS: 91.7%), but patients who had first year treatment breaks > 14 days, particularly permanent cessation of ibrutinib had both reduced 1 year OS (68.5%) and also a statistically significant excess mortality rate beyond one year. Although outcomes appear inferior to the RESONATE trial (1 year OS;90%: PFS;84%), this may partly reflect the inclusion of PS 2+ patients and that 17.5% of patients permanently discontinued ibrutinib due to an event other than disease progression

Microfluidics: reframing biological enquiry

The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science

Real-time size modulation and synchronization of a microfluidic dropmaker with pulsed surface acoustic waves (SAW)

We show that a microfluidic flow focusing drop maker can be synchronized to a surface acoustic waves (SAW) triggered by an external electric signal. In this way droplet rate and volume can be controlled over a wide range of values in real time. Using SAW, the drop formation rate of a regularly operating water in oil drop maker without SAW can be increased by acoustically enforcing the drop pinch-off and thereby reducing the volume. Drop makers of square cross-sections (w = h = 30 µm, with width w and height h) that produce large drops of length l = 10 w can be triggered to produce drops as short as l ~ 2w, approaching the geometical limit l = w without changing the flow rates. Unlike devices that adjust drop size by changing the flow rates the acoustic dropmaker has very short transients allowing to adjust the size of every single drop. This allows us to produce custom made emulsions with a defined size distribution as demonstrated here not only for a monodisperse emulsion but also for binary emulsions with drops of alternating size. Moreover, we show that the robustness and monodispersity of our devices is enhanced compared to purely flow driven drop makers in the absence of acoustic synchronization