Plasma microbial cell-free DNA following chimeric antigen receptor T cell therapy in pediatric patients with relapsed/refractory leukemia.

Chimeric antigen receptor (CAR) T cell therapy is a promising treatment for pediatric patients with relapsed or refractory B cell acute lymphoblastic leukemia (R/R B ALL). Cytokine release syndrome (CRS) is a common toxicity after CAR T cell therapy and fever is often the first symptom. Differentiating CRS from infection after CAR T cell therapy can be challenging. Plasma microbial cell free DNA (mcfDNA) is a novel diagnostic tool which allows for qualitative and quantitative assessment of over 1000 organisms. This pilot study sought to characterize mcfDNA results in pediatric patients with R/R B ALL in the first 2 months after CAR T cell therapy.

Advances in the Care of Infants With Prenatal Opioid Exposure and Neonatal Opioid Withdrawal Syndrome.

A significant number of advances have been made in the last 5 years with respect to the identification, diagnosis, assessment, and management of infants with prenatal opioid exposure and neonatal opioid withdrawal syndrome (NOWS) from birth to early childhood. The primary objective of this review is to summarize major advances that will inform the clinical management of opioid-exposed newborns and provide an overview of NOWS care to promote the implementation of best practices. First, advances with respect to standardizing the clinical diagnosis of NOWS will be reviewed. Second, the most commonly used assessment strategies are discussed, with a focus on presenting new quality improvement and clinical trial data surrounding the use of the new function-based assessment Eat, Sleep, and Console approach. Third, both nonpharmacologic and pharmacologic treatment modalities are reviewed, highlighting clinical trials that have compared the use of higher calorie and low lactose formula, vibrating crib mattresses, morphine compared with methadone, buprenorphine compared with morphine or methadone, the use of ondansetron as a medication to prevent the need for NOWS opioid pharmacologic treatment, and the introduction of symptom-triggered dosing compared with scheduled dosing. Fourth, maternal, infant, environmental, and genetic factors that have been found to be associated with NOWS severity are highlighted. Finally, emerging recommendations on postdelivery hospitalization follow-up and developmental surveillance are presented, along with highlighting ongoing and needed areas of research to promote infant and family well-being for families impacted by opioid use.

Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA.

Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer.