M. Brooke Bernhardt

Oral iron chelation and the treatment of iron overload in a pediatric hematology center

Recent advances have led to the development of oral iron chelators, which have changed clinical practice. The objective of this study was to descriptively assess the use of one such agent, deferasirox, as standard of care treatment in a large pediatric hematology center.

Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors: A report of the Children's Oncology Group

To determine the MTD of Seneca Valley Virus (NTX‐010) in children with relapsed/refractory solid tumors. Patients (≥3–≤21 years) with neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features were eligible.

An Outbreak of Burkholderia cepacia Complex Infections Associated with Contaminated Liquid Docusate

OBJECTIVE To investigate an outbreak of Burkholderia cepacia complex and describe the measures that revealed the source. SETTING A 629-bed, tertiary-care, pediatric hospital in Houston, Texas. PATIENTS Pediatric patients without cystic fibrosis (CF) hospitalized in the pediatric and cardiovascular intensive care units. METHODS We investigated an outbreak of B. cepacia complex from February through July 2016. Isolates were evaluated for molecular relatedness with repetitive extragenic palindromic polymerase chain reaction (rep-PCR); specific species identification and genotyping were performed at an independent laboratory. The investigation included a detailed review of all cases, direct observation of clinical practices, and respiratory surveillance cultures. Environmental and product cultures were performed at an accredited reference environmental microbiology laboratory. RESULTS Overall, 18 respiratory tract cultures, 5 blood cultures, 4 urine cultures, and 3 stool cultures were positive in 24 patients. Among the 24 patients, 17 had symptomatic infections and 7 were colonized. The median age of the patients was 22.5 months (range, 2-148 months). Rep-PCR typing showed that 21 of 24 cases represented the same strain, which was identified as a novel species within the B. cepacia complex. Product cultures of liquid docusate were positive with an identical strain of B. cepacia complex. Local and state health departments, as well as the CDC and FDA, were notified, prompting a multistate investigation. CONCLUSIONS Our investigation revealed an outbreak of a unique strain of B. cepacia complex isolated in clinical specimens from non-CF pediatric patients and from liquid docusate. This resulted in a national alert and voluntary recall by the manufacturer. Infect Control Hosp Epidemiol 2017;38:567-573.

Use of allopurinol in children with acute lymphoblastic leukemia to reduce skewed thiopurine metabolism

Mercaptopurine (6‐MP), a critical component of acute lymphoblastic leukemia (ALL) therapy, is metabolized to 6‐thioguanine (6‐TGN) which is responsible for its anti‐leukemic effect, and to 6‐methylmercaptopurine nucleotides (6‐MMPN/6‐MMP) which can be hepatotoxic. Some patients preferentially metabolize 6‐MP to 6‐MMPN which may increase the risk of liver injury, reduce serum levels of 6‐TGN and potentially increase the risk of relapse. The addition of allopurinol to oral 6‐MP has been shown to optimize metabolism towards 6‐TGN in patients with inflammatory bowel disease (IBD); however, this use has not been reported in patients undergoing treatment for ALL. Pediatr Blood Cancer 2014;61:1114–1117.

Agreement among measurements and estimations of glomerular filtration in children with cancer

Glomerular filtration is an important route of elimination for many types of chemotherapy. Accurate estimation of glomerular filtration at the bedside is essential in the management of children with cancer. Bedside formulae for the estimation of glomerular filtration have not been validated in children with cancer. We investigated the accuracy of three formulae (the original Schwartz, Counahan‐Barratt, and revised Schwartz equations) against measurement of the glomerular filtration rate (GFR) in a cohort of children with cancer.

The impact of chemotherapy shortages on COG and local clinical trials: a report from the Children's Oncology Group.

Oncology drug shortage is associated with increased patient adverse events and decreased enrollment on clinical trials for adult patients; however, the impact of oncology drug shortages has not been well studied in children with cancer.

Bending the Cost Curve in Childhood Cancer.

Healthcare for children with cancer costs significantly more than other children. Cost reduction efforts aimed toward relatively small populations of patients that use a disproportionate amount of care, like childhood cancer, could have a dramatic impact on healthcare spending. The aims of this review are to provide stakeholders with an overview of the drivers of financial costs of childhood cancer and to identify possible directions to curb or decrease these costs. Costs are incurred throughout the spectrum of care. Recent trends in pharmaceutical costs, evidence identifying the contribution of administration costs, and overuse of surveillance studies are described. Awareness of cost and value, i.e., the outcome achieved per dollar or burden spent, in delivery of care and research is necessary to bend the cost curve. Incorporation of these dimensions of care requires methodology development, prioritization, and ethical balance.

Using decision modeling to guide drug allocation during a shortage.

Drug shortages require clinical teams to decide how to allocate drugs in limited supply among their patients. Ethical frameworks are invaluable for promoting rational approaches to drug distribution, but gaps remain between ethical theory and clinical application. The goal of this work was to explore how decision modeling could supplement ethical frameworks to inform drug distribution from the perspective of a clinical team.

Treatment-related sinusoidal obstruction syndrome in children with de novo acute lymphoblastic leukemia during intensification

PurposeSinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, has been described following treatment of acute lymphoblastic leukemia (ALL) with the anti-metabolite 6-thioguanine (6-TG). Previous studies incorporating daily 6-TG into maintenance chemotherapy demonstrated a high incidence of SOS, typically presenting after prolonged exposures to 6-TG. 6-TG continues to be used as a single, 14-day burst during intensification; however, SOS associated with brief courses of 6-TG is poorly described. We aim to describe this rare though clinically significant phenomenon.MethodsChildren with 6-TG-related SOS were retrospectively identified from 680 de novo patients with ALL at Texas Children’s Cancer Center over 8 years. Clinical characteristics and outcomes are described.ResultsTen (1.5%) patients were identified with SOS. No predominant sex, ethnicity, or race was noted. SOS was diagnosed 16.5 (6–42) days from starting 6-TG. Isolated thrombocytopenia (IT) was noted in 9/10 patients and presented a median of 5 days prior to SOS. Refractoriness to platelet transfusions was noted in 8/10 patients, presenting a median of 2 days prior to SOS. Most patients were otherwise clinically stable outpatients upon presenting with IT or transfusion refractoriness. Fever was noted in 7/10 patients at diagnosis and 6/10 had documented or suspected infection within 14 days of SOS. Two patients died, while eight fully recovered. Intermediate thiopurine methyltransferase genotype was noted in 5/8 patients with data available.ConclusionSOS following short courses of 6-TG in DI is clinically distinct from SOS following prolonged courses of 6-TG in maintenance, particularly in its early presentation and outcomes.

Evaluation of opioid prescribing after rescheduling of hydrocodone-containing products

Purpose. Institutional prescribing trends of hydrocodone‐containing products (HCPs) before and after the Drug Enforcement Administrations rescheduling of HCPs were evaluated. Methods. A retrospective evaluation was performed on 6 oral opioid analgesics on the hospital formulary that were prescribed to patients treated at Texas Childrens Hospital and Pavilion for Women for the 6 months before and after the rescheduling of HCPs on October 6, 2014. Patients were eligible for inclusion if they were prescribed any of the following oral agents: HCPs (e.g., hydrocodone with acetaminophen), codeine‐containing products (e.g., codeine, codeine with acetaminophen), morphine, hydromorphone, oxycodone‐containing products (e.g., oxycodone, oxycodone with acetaminophen), and tramadol. Results. During the 12‐month study period, a total of 38,928 inpatient orders and outpatient prescriptions were processed for the studied agents in both locations; the majority were orders for inpatients. An overall reduction in the total number of opioid prescriptions was observed after the rescheduling of HCPs. Substantial increases in the proportional use of codeine were observed in all 4 settings after HCP rescheduling. Data for each of the agents revealed a shift in prescribing patterns centered along the HCP rescheduling date of October 6, 2014, and revealed a decrease in HCP use across all areas with an accompanying increase in codeine‐containing products, oxycodone‐containing products, and tramadol. Conclusion. The rescheduling of HCPs resulted in a reduction in HCP prescriptions but was accompanied by increases in the use of codeine‐containing products and tramadol in all settings.