Brincidofovir (BCV) is a lipid conjugate of cidofovir with good oral bioavailability, enabling optimal intracellular levels of the active drug. Lower rates of nephrotoxicity and myelotoxicity make it a favorable alternative. Despite a greater safety profile among pediatric hematopoietic cell transplant recipients, the oral formulation has been associated with increased gastrointestinal toxicity in adult hematopoietic cell transplant recipients. Oral BCV continues to be developed as a countermeasure against smallpox, while a potentially safer intravenous preparation has been out licensed to another company. BCV has demonstrated great in vitro potency against double-stranded DNA viruses, especially adenovirus. Because of its importance for immunocompromised patients, this review aims to evaluate BCV’s clinical and safety profile to support its continued development.

Graft-versus-host-disease (GVHD) is one of the leading causes of non-relapse mortality (NRM) following allogeneic hematopoietic cell transplantation (alloHCT). Post-transplant cyclophosphamide (PTCy) has shown promise in managing GVHD. However, cyclophosphamide has known cardiac toxicities and few studies have evaluated the cardiac toxicities that arise following PTCy. Here, we completed a retrospective analysis of matched alloHCT patients at our institution who received PTCy or non-PTCy-based GVHD prophylaxis, with the goal of determining the incidence of cardiac toxicities up to 100 days after alloHCT. We included 585 patients in our analysis and found that 38 patients (6.5%) experienced cardiac toxicities after alloHCT. The toxicities observed included arrhythmias (n=21), heart failure (n=14), pericardial effusions (n=10), and myocardial infarction or ischemia (n=7). Patients who received PTCy had a 7.4% incidence of cardiac toxicities, while non-PTCy patients had an incidence of 5.8% (p=0.4). We found that age > 55 years (p=0.02), history of hypertension (p=0.01), arrhythmia (p=0.003), diabetes (p=0.04), and cardiac comorbidities (p<0.001) were significant predictors of cardiac toxicity, while none of the preparative and GVHD prophylaxis regimens used were predictive of cardiac toxicity. From these findings, we proposed the use of a Cardiac Risk Stratification Score to quantify the risk of cardiac toxicity following alloHCT and found that a higher score correlated with cardiac toxicity incidence. Furthermore, the development of cardiac toxicity was associated with worse 1-yr overall survival (OS) and NRM while the use of PTCy was associated with improvements in 1-year OS and NRM rates.

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Patients with hematologic malignancies or hematopoietic cell transplants who had febrile neutropenia demonstrated homogeneous calculated cefepime volumes and clearances. The population parameters presented in this study may aid in the calculation of patient-specific fT>MIC for similar patients.