DPYD genotype should be extended to rare variants: report on two cases of phenotype / genotype discrepancy.

The enzyme dihydropyrimidine dehydrogenase (DPD) is the primary catabolic pathway of fluoropyrimidines including 5 fluorouracil (5FU) and capecitabine. Cases of lethal toxicity have been reported in cancer patients with complete DPD deficiency receiving standard dose of 5FU or capecitabine. DPD is encoded by the pharmacogene DPYD in which more than 200 variants have been identified.

Monocentric experience of venetoclax-based regimen in paediatric refractory and relapsed AML/MDS.

BCL-2 inhibitor venetoclax demonstrates promising efficacy in paediatric relapsed/refractory acute myeloid leukaemia (r/r AML). This retrospective analysis evaluated 12 patients treated with venetoclax-based regimens under compassionate use for r/r myeloid malignancies. The overall response rate (ORR) was 41.

Exposure toxicity of venetoclax in acute myeloid leukemia patients in the real-life setting: impact of high exposure on delayed neutropenia.

Not available.

Effect of ultrasound-mediated blood-spinal cord barrier opening on survival and motor function in females in an amyotrophic lateral sclerosis mouse model.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. The limited efficacy of recent therapies in clinical development may be linked to lack of drug penetration to the affected motor neurons due to the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB).

Methods: In this work, the safety and efficacy of repeated short transient opening of the BSCB by low intensity pulsed ultrasound (US, sonication) was studied in females of an ALS mouse model (B6.

Cerebrospinal fluid distribution and pharmacokinetics of ponatinib in Ph1+ acute lymphoblastic leukemia.

Tyrosine kinase inhibitors efficacy in central nervous system (CNS) disease remains uncertain. Ponatinib was studied for CNS distribution in 16 patients with Philadelphia-positive acute lymphoblastic leukemia. Cerebrospinal fluid concentrations fell below the 40 nM threshold, suggesting suboptimal CNS exposure.