A genetic etiology is identifiable in 20%–30% of patients with congenital heart defects (CHD). Chromosomal microarray analysis (CMA) can detect copy number variants (CNV) associated with CHD. In previous studies, the diagnostic yield of postnatal CMA testing ranged from 4% to 28% in CHD patients. However, incidental pathogenic CNV and variants of unknown significance are often discovered without any known association with CHD. The study objective was to describe the rate of pathogenic CNV associated with neurodevelopmental impairment (NDI) and compare clinical findings in CHD neonates with genetic results. A single‐center retrospective review was performed on all consecutive newborns with CHD admitted to a tertiary neonatal intensive care unit from January 2013 to March 2019 (n = 525). CHD phenotypes were classified as per the National Birth Defect Prevention Study. CMA detected pathogenic CNV in 21.3% (61/287) of neonates, and karyotype or fluorescence in situ hybridization detected aneuploidies in an additional 11% of the overall cohort (58/525). Atrioventricular septal defects and conotruncal defects showed the highest diagnostic yield by CMA (28.6% and 27.2%, respectively). Among neonates with pathogenic CNV on CMA, 78.7% (48/61) were associated with NDI. Neonates with pathogenic CNV were smaller in length at birth compared to those with benign CNV or variants of unknown significance (p = 0.005) and were more likely to be discharged with an enteral feeding tube (p = 0.027). CMA can discover genetic variants associated with NDI and are common in neonates with CHD. Genetic testing in the neonatal period can heighten awareness of genetic risk for NDI.

Conditioning regimens contribute significantly to outcomes following allogeneic stem cell transplantation (allo-SCT). Reduced-intensity conditioning (RIC) regimens provide lower toxicity at the cost of reduced efficacy compared with myeloablative conditioning (MAC) regimens. However, because pre-transplant prognostic variables often determine the conditioning regimen, studies of RIC vs. MAC have been inconclusive. We present a retrospective analysis of 242 acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients, 112 of whom were in 56 pairs matched using propensity scores, to account for variation that may confound clinical outcomes. The uniform conditioning regimens consisted of fludarabine with pharmacokinetic (PK)-guided intravenous busulfan (Bu). The RIC and MAC regimens were dosed at the average daily area under the concentration-vs-time curve (AUC) of 4000 µMol min and 5000-6000 µMol min, or total course AUC of 16,000 µMol min and 20,000-24,000 µMol min, respectively; PK-guided dosing removes overlap in systemic Bu exposure. When patients' data were propensity-matched, there was a trend toward significantly increased full donor chimerism and decreased chronic graft vs. host disease in RIC, and no significant differences in progression free survival and overall survival between RIC and MAC. Our results also elucidate the efficacy of PK-guided-dosing in the setting of allo-SCT for AML and MDS.

No abstract

No abstract