Comparison of variants in TPMT and NUDT15 between sequencing and genotyping methods in a multistate pediatric institution.

The risk of severe adverse events related to thiopurine therapy can be reduced by personalizing dosing based on TPMT and NUDT15 genetic polymorphisms. However, the optimal genetic testing platform has not yet been established. In this study, we report on the TPMT and NUDT15 genotypes and phenotypes generated from 320 patients from a multicenter pediatric healthcare system using both Sanger sequencing and polymerase chain reaction genotyping (hereafter: genotyping) methods to determine the appropriateness of genotyping in our patient population. Sanger sequencing identified variant TPMT alleles including *3A (8, 3.2% of alleles), *3C (4, 1.6%), and *2 (1, 0.4%), and NUDT15 alleles including *2 (5, 3.6%) and *3 (1, 0.7%). For genotyped patients, variants identified in TPMT included *3A (12, 3.1%), *3C (4, 1%), *2 (2, 0.5%), and *8 (1, 0.25%), whereas NUDT15 included *4 (2, 1.9%) and *2 or *3 (1, 1%). Between Sanger sequencing and genotyping, no significant difference in allele, genotype, or phenotype frequency was identified for either TPMT or NUDT15. All patients who were tested using Sanger sequencing would have been accurately phenotyped for either TPMT (124/124), NUDT15 (69/69), or both genes (68/68) if they were assayed using the genotyping method. Considering 193 total TPMT and NUDT15 Sanger Sequencing tests reviewed, all tests would have resulted in an appropriate clinical recommendation if the test had instead been conducted using the comparison genotyping platforms. These results suggest that, in this study population, genotyping would be sufficient to provide accurate phenotype calls and clinical recommendations.

Enteral Nutrition in Pediatric High-risk Head and Neck Cancer Patients Receiving Proton Therapy: Identifying Risk Factors and Quality of Life Concerns to Optimize Care.

BACKGROUND: Radiotherapy for pediatric head and neck tumors often results in mucositis and pain, limiting oral intake and compromising patients' nutrition. There are little pediatric data available regarding enteral tube use and risk factors. Our objective was to estimate nutrition needs, identify risk factors contributing to nutritional decline and explore quality of life measures regarding enteral nutrition during proton radiotherapy. PROCEDURE: Nutritional metrics and status were collected throughout radiation treatment for 32 patients. We surveyed patients/caregivers about their perceptions of enteral nutrition. Risk factors for progression to non-oral nutrition or >5% weight loss were evaluated using univariate analysis. RESULTS: Patients who received any esophageal radiation or >30 Gy mean dose to the pharyngeal constrictors were more likely to experience >5% weight loss. These patients, as well as those who received a mean dose >30 Gy to the oropharynx or concurrent chemotherapy, were also more likely to require non-oral supplementation. Patients expressed the importance of maximizing nutrition and feared pain associated with a tube placement. CONCLUSIONS: Pediatric patients with head and neck cancer can be risk-stratified based on clinical and dosimetric factors. This data, combined with parent and patient perceptions, is key to the development of rational guidelines.

A Case of Hemophagocytic Lymphohistiocytosis and Kawasaki Disease: Concurrent or Overlapping Diagnoses?

Hemophagocytic lymphohistiocytosis (HLH) is not always suspected at the time of presentation. It is often mistaken for other diagnoses; complicated by the fact that it is often associated with an inciting event that has significant overlap. Kawasaki disease, along with other disorders, such as Ebstein Barr Virus infection, are conditions that may lead HLH. Our patient had a presentation that was consistent with Kawasaki disease on initial presentation, however subsequently met the diagnostic criteria of HLH. It provided an interesting discussion about diagnoses with clinical criteria and how the overlap can sometimes delay or complicate initial diagnosis.

False Lung Metastasis: Concurrent Ewing Sarcoma and Minimally Invasive Adenocarcinoma.

Pediatric lung cancer is a very rare occurrence, particularly as a primary lesion. A concurrent diagnosis is even more unusual and only reported a handful of times in Ewing sarcoma. Our patient is a 13-year-old boy who had concurrent diagnoses of Ewing sarcoma and minimally invasive adenocarcinoma of the lung, formerly bronchoalveolar carcinoma. To our knowledge this has also been found in at least 1 other case. There are some classic genetic mutations associated with Ewing sarcoma. None have been found to be linked with the concurrent diagnosis. A biological linkage is worth considering.