Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy.

Gilteritinib is the current standard of care for relapsed or refractory fms related receptor tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia in many countries, however outcomes for patients relapsing after contemporary first-line therapies (intensive chemotherapy with midostaurin, or nonintensive chemotherapy with venetoclax) are uncertain. Moreover, reported data on toxicity and health care resource use is limited. Here, we describe a large real-world cohort of 152 patients receiving single-agent gilteritinib in 38 UK hospitals.

Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based nonintensive therapy.

Assessment of measurable residual disease (MRD) by quantitative reverse transcription polymerase chain reaction is strongly prognostic in patients with NPM1-mutated acute myeloid leukemia (AML) treated with intensive chemotherapy; however, there are no data regarding its utility in venetoclax-based nonintensive therapy, despite high efficacy in this genotype. We analyzed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved complete remission (CR)/CR with incomplete hematological recovery following treatment with venetoclax and hypomethylating agents (HMAs) or low-dose cytarabine (LDAC). A total of 44 patients (58%) achieved bone marrow (BM) MRD negativity, and a further 14 (18%) achieved a reduction of ≥4 log10 from baseline as their best response, with no difference between HMAs and LDAC.

Three-Dimensionally Printed Simulated Tracheas to Improve Cricothyrotomy Skills Among Anesthesia Providers.

Cricothyrotomy proficiency is imperative for anesthesia providers; however, opportunities to perform this skill are infrequent making skill maintenance essential. Increased accessibility of three-dimensional (3D) printing allows for production of low-cost simulation models. The models used for simulation-based teaching and deliberate practice facilitate skill development and refinement.

Phylogenetic and geographical analysis of a retrovirus during the early stages of endogenous adaptation and exogenous spread in a new host.

Most retroviral endogenization and host adaptation happened in the distant past, with the opportunity to study these processes as they occurred lost to time. An exception exists with the discovery that koala retrovirus (KoRV) has recently begun its endogenization into the koala (Phascolarctos cinereus) genome. What makes this opportunity remarkable is the fact that Northern Australian koalas appear to be undergoing endogenization with one KoRV subtype (KoRV-A), while all subtypes (KoRV-A-I) coexist exogenously, and Southern Australian koalas appear to carry all KoRV subtypes as an exogenous virus.

FLT3 Inhibition in Acute Myeloid Leukaemia - Current Knowledge and Future Prospects.

Activating mutations of FMS-like tyrosine kinase 3 (FLT3) are present in 30% of acute myeloid leukaemia (AML) patients at diagnosis and confer an adverse clinical prognosis. Mutated FLT3 has emerged as a viable therapeutic target and a number of FLT3-directed tyrosine kinase inhibitors have progressed through clinical development over the last 10-15 years. The last two years have seen United States Food and Drug Administration (US FDA) approvals of the multi-kinase inhibitor midostaurin for newly-diagnosed FLT3-mutated patients, when used in combination with intensive chemotherapy, and of the more FLT3-selective agent gilteritinib, used as monotherapy, for patients with relapsed or treatment-refractory FLT3-mutated AML.