T-cell replete cord transplants give superior outcomes in high-risk and relapsed/refractory pediatric myeloid malignancy.

Stem cell transplant (SCT) outcomes in high-risk and relapsed/refractory (R/R) pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have been historically poor. Cord blood (CB) allows T-cell replete CB transplant (TRCB), enabling enhanced graft-versus-leukemia. We consecutively collected data from 367 patients undergoing TRCB (112 patients) or other cell source (255 patients) SCT for pediatric AML/MDS in the United Kingdom and Ireland between January 2014 and December 2021. Data were collected about the patient's demographics, disease, and its treatment; including previous transplant, measurable residual disease (MRD) status at transplant, human leukocyte antigen-match, relapse, death, graft versus host disease (GvHD), and transplant-related mortality (TRM). Univariable and multivariable analyses were undertaken. There was a higher incidence of poor prognosis features in the TRCB cohort: 51.4% patients were MRD positive at transplant, 46.4% had refractory disease, and 21.4% had relapsed after a previous SCT, compared with 26.1%, 8.6%, and 5.1%, respectively, in the comparator group. Event free survival was 64.1% within the TRCB cohort, 50% in MRD-positive patients, and 79% in MRD-negative patients. To allow for the imbalance in baseline characteristics, a multivariable analysis was performed where the TRCB cohort had significantly improved event free survival, time to relapse, and reduced chronic GvHD, with some evidence of improved overall survival. The effect appeared similar regardless of the MRD status. CB transplant without serotherapy may be the optimal transplant option for children with myeloid malignancy.

Clinical pharmacology of antifungal agents in pediatrics: children are not small adults.

The optimal dosage information to improve the prognosis of invasive fungal infections in children and neonates is still limited and current dosing strategies are supported mainly by adult studies and extrapolation. Significant progress has been made to address this need in the last decade. Pre-clinical models and pharmacokinetic-pharmacodynamic (PK-PD) bridging studies supported by pediatric pharmacokinetic studies have investigated optimal dosing regimens for neonates and children. Here, we review the rationale for various antifungal regimens in infants and children.

Adverse drug reactions in neonates: could we be documenting more?

Neonates are vulnerable to adverse drug reactions but reports of these events are relatively infrequent. Reporting can be increased by adapting a number of standard techniques to the unique features of neonatal care and pathology. However, clinicians and parents will be reluctant to report information about harms in the absence of mechanisms to ensure that reports affect clinical practice. Improved reporting will depend on education and cultural change that are informed by research about pharmacovigilance in neonatal settings. The efficient use of neonatal adverse drug reaction reports will require harmonization of terminology and interoperable databases.