Pediatric Chronic Myeloid Leukemia Presenting With Extreme Thrombocytosis Simulating Essential Thrombocythemia.

A 10-year-old boy presented with spontaneous bruising and was found to have extreme thrombocytosis without neutrophilia/shift to immaturity, basophilia or eosinophilia. While the peripheral blood and bone marrow findings initially suggested essential thrombocythemia, BCR-ABL1 translocation was detected and chronic myeloid leukemia, chronic phase, was diagnosed. Apheresis for platelet depletion was performed as a bridge given the delayed effects of medical therapy.

Stereotactic Body Radiation Therapy and Concurrent Targeted Therapy for Lung Metastases in Pediatric Sarcoma.

Purpose: The purpose of this investigation was to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) for pulmonary metastases from pediatric sarcomas. Methods and Materials: This study was a single institutional retrospective chart review including patients younger than 21 years of age at diagnosis who had received SBRT for pulmonary metastasis from metastatic sarcoma. Our current electronic record system was queried for all eligible patients. Primary endpoint was tumor response as defined by Respone Evaluation Criteria in Solid Tumors 1.1 criteria. Secondarily, we analyzed factors that affected tumor response as well as toxicity of treatment. Median dose was 50 Gy ranging from 30 to 60 Gy in 5 fractions to the planning tumor volume. Results: There were 7 patients, ranging in age from 6 to 21 years with a total of 14 pulmonary lesions treated with SBRT. Median and mean follow-up times for the 7 patients were 10.6 months and 15.9 months, respectively. The complete response rate was 50%, partial response 21%, stable disease 21%, and progressive disease 7%. Four of the 7 patients were treated with concurrent systemic therapy, 3 of which were targeted oral therapies. Additionally, we observed that patients who were on targeted therapy such as regorafenib or pazopanib seemed to have better local control compared with patients without targeted therapy. Conclusions: With an overall response rate of 92%, SBRT provided a noninvasive effective palliative treatment option with few side effects in this small retrospective study of 7 patients. A larger prospective clinical trial is warranted to evaluate the role of SBRT in the treatment of unresectable metastatic pediatric sarcomas.

Analysis of recurrently protected genomic regions in cell-free DNA found in urine.

Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, urine cfDNA is highly fragmented. Whether characteristics of these fragments reflect underlying genomic architecture is unknown. Here, we characterized fragmentation patterns in urine cfDNA using whole-genome sequencing. Size distribution of urine cfDNA fragments showed multiple strong peaks between 40 and 120 base pairs (bp) with a modal size of 81- and sharp 10-bp periodicity, suggesting transient protection from complete degradation. These properties were robust to preanalytical perturbations, such as at-home collection and delay in processing. Genome-wide sequencing coverage of urine cfDNA fragments revealed recurrently protected regions (RPRs) conserved across individuals, with partial overlap with nucleosome positioning maps inferred from plasma cfDNA. The ends of cfDNA fragments clustered upstream and downstream of RPRs, and nucleotide frequencies of fragment ends indicated enzymatic digestion of urine cfDNA. Compared to plasma, fragmentation patterns in urine cfDNA showed greater correlation with gene expression and chromatin accessibility in epithelial cells of the urinary tract. We determined that tumor-derived urine cfDNA exhibits a higher frequency of aberrant fragments that end within RPRs. By comparing the fraction of aberrant fragments and nucleotide frequencies of fragment ends, we identified urine samples from cancer patients with an area under the curve of 0.89. Our results revealed nonrandom genomic positioning of urine cfDNA fragments and suggested that analysis of fragmentation patterns across recurrently protected genomic loci may serve as a cancer diagnostic.