The advent of digital, electronic, and molecular technologies has allowed the study of complete genomes. Integrating this information into drug development has opened the door for pharmacogenomic (PGx) interventions in direct patient care. PGx allows clinicians to better identify drug of choice and optimize dosing regimens based on an individual's genetic characteristics. Integrating PGx into pediatric care is a priority for the Sanford Children's Genomic Medicine Consortium, a partnership of ten children's hospitals across the US committed to the innovation and advancement of genomics in pediatric care. In this white paper, we review the current state of PGx research and its clinical utility in pediatrics, a largely understudied population, and make recommendations for advancing cutting-edge practice in pediatrics.

We prospectively evaluated tumour response and renal function in 12 newly-diagnosed children with high-risk Wilms tumour receiving ifosfamide, carboplatin, and etoposide (ICE) chemotherapy. Two cycles of ICE were followed by 5 weeks of vincristine, dactinomycin, and doxorubicin (Adriamycin) (VDA), and nephrectomy, radiotherapy, additional VDA, and a third ICE cycle. Carboplatin dosage was based on glomerular filtration rate (GFR) to achieve targeted systemic exposure (6 mg/ml × min). Mean GFR (measured by technetium 99m-DTPA clearance) declined by 7% after 2 cycles of ICE and by 38% after nephrectomy; the mean carboplatin dose was reduced 32% after nephrectomy. Mean GFR remained stable after the third ICE cycle. Although urinary β 2 -microglobulin excretion increased during therapy, no patient had clinically significant renal tubular dysfunction at the end of treatment.Treatment with ICE, nephrectomy, and radiotherapy significantly reduces GFR, largely as the result of nephrectomy. Adjustment of carboplatin dosage on the basis of GFR and careful monitoring of renal function may alleviate nephrotoxicity.

Background and Objective Monitoring renal function is critical in treating pediatric patients, especially when dosing nephrotoxic agents. We evaluated the validity of the bedside Schwartz and Brandt equations in pediatric oncology patients, and developed new equations for estimated glomerular filtration rate (GFR) in these patients. Methods A retrospective analysis was conducted on patients comparing the estimated GFR using the bedside Schwartz and Brandt equations to measured GFR (mGFR) from 99mTechnetium-DPTA (99mTc-DTPA) between January 2007 and August 2013. An improved equation to estimate GFR was developed, simplified, and externally validated in a cohort of patients studied from September 2013 to June 2015. Carboplatin doses calculated from 99mTc-DTPA were compared to doses calculated by GFR estimating equations. Results Overall, the bedside Schwartz and Brandt equations did not precisely or accurately predict mGFR in our pediatric oncology patient population. Using a subset of the data, we developed a 5-covariate equation, which included the covariates of height, serum creatinine, age, BUN, and gender, and a simplified version (2-covariates), which only contained height and serum creatinine. These equations were used to estimate GFR in 2036 studies, resulting in precise and accurate predictors of the mGFR values. The equations were validated in an external cohort of 570 studies; both new equations were more accurate in calculating carboplatin doses than either the bedside Schwartz or Brandt equation. Conclusions Two new equations were developed to estimate GFR in pediatric oncology patients, both of which did a better job at estimating mGFR than published equations.

The level of systemic exposure in our anephric patient was comparable to or lower than that achieved in patients with normal renal function at similar dosages. The patient tolerated therapy without problems. It appears that pediatric patients in renal failure can be treated with paclitaxel as a 24-h continuous infusion at doses similar to those used in patients with normal renal function.

Several healthcare organizations across Minnesota have developed formal pharmacogenomic (PGx) clinical programs to increase drug safety and effectiveness. Healthcare professional and student education is strong and there are multiple opportunities in the state for learners to gain workforce skills and develop advanced competency in PGx. Implementation planning is occurring at several organizations and others have incorporated structured utilization of PGx into routine workflows. Laboratory-based and translational PGx research in Minnesota has driven important discoveries in several therapeutic areas. This article reviews the state of PGx activities in Minnesota including educational programs, research, national consortia involvement, technology, clinical implementation and utilization and reimbursement, and outlines the challenges and opportunities in equitable implementation of these advances.