Individuals harboring germ-line DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 Syndrome or pleuropulmonary blastoma-familial tumor and dysplasia syndrome [online Mendelian inheritance in man (OMIM) #601200]. In addition, specific somatic mutations in the DICER1 RNase III catalytic domain have been identified in several DICER1-associated tumor types. Pituitary blastoma (PitB) was identified as a distinct entity in 2008, and is a very rare, potentially lethal early childhood tumor of the pituitary gland. Since the discovery by our team of an inherited mutation in DICER1 in a child with PitB in 2011, we have identified 12 additional PitB cases. We aimed to determine the contribution of germ-line and somatic DICER1 mutations to PitB. We hypothesized that PitB is a pathognomonic feature of a germ-line DICER1 mutation and that each PitB will harbor a second somatic mutation in DICER1. Lymphocyte or saliva DNA samples ascertained from ten infants with PitB were screened and nine were found to harbor a heterozygous germ-line DICER1 mutation. We identified additional DICER1 mutations in nine of ten tested PitB tumor samples, eight of which were confirmed to be somatic in origin. Seven of these mutations occurred within the RNase IIIb catalytic domain, a domain essential to the generation of 5p miRNAs from the 5′ arm of miRNA-precursors. Germ-line DICER1 mutations are a major contributor to PitB. Second somatic DICER1 “hits” occurring within the RNase IIIb domain also appear to be critical in PitB pathogenesis.

In pediatric patients with lesser risk ALL, internal lines (ports) should be the preferred CVL type due to a lower risk of infectious and thrombotic complications. In addition, CVLs placed early in induction are associated with a higher risk of positive blood culture than those placed later in induction.

Music is widely used to enhance well-being. We wished to assess music’s effect on pediatric oncology outpatients. Patients who had leukemia and were in maintenance or consolidation outpatient treatment served as their own control at two visits. At visit 1, children rested for 20 min; at visit 2, for 20 min they listened to music designed to increase vitality and improve heart rate variability (HRV). At both visits, parents completed before and after treatment visual analog scales (VAS) of their child’s relaxation, well-being, vitality, anxiety, stress, and depression; patients’ heart rates were monitored during treatments to calculate HRV. The 47 patients with complete VAS data and 34 patients with usable HRV data were similar. At baseline, VAS scores for negative states were low (average <2.5 of 10) and positive states were high (average 7> of 10). Relaxation improved more with music than rest (p < 0.01). The HRV parasympathetic parameter was significantly lower with music than rest. No other differences were significant. Further studies are needed to better delineate the relationship between subjective and objective measures of well-being among patients who are not in severe distress.

Use of CAM is common among pediatric oncology patients and often is not discussed with the treating physician(s). Patients from very religious families are more likely to use CAM.

Wilms tumor is the most common childhood renal cancer. To identify mutations that predispose to Wilms tumor, we are conducting exome sequencing studies. Here we describe 11 different inactivating mutations in the REST gene (encoding RE1-silencing transcription factor) in four familial Wilms tumor pedigrees and nine non-familial cases. Notably, no similar mutations were identified in the ICR1000 control series (13/558 versus 0/993; P < 0.0001) or in the ExAC series (13/558 versus 0/61,312; P < 0.0001). We identified a second mutational event in two tumors, suggesting that REST may act as a tumor-suppressor gene in Wilms tumor pathogenesis. REST is a zinc-finger transcription factor that functions in cellular differentiation and embryonic development. Notably, ten of 11 mutations clustered within the portion of REST encoding the DNA-binding domain, and functional analyses showed that these mutations compromise REST transcriptional repression. These data establish REST as a Wilms tumor predisposition gene accounting for ∼2% of Wilms tumor.

Sirolimus is an effective therapy for children with kaposiform hemangioendothelioma with or without the Kasabach-Merritt phenomenon. We report the case of a child with kaposiform hemangioendothelioma and the Kasabach-Merritt phenomenon who developed pneumonia (PCP) while on sirolimus and a prednisolone taper, after lack of adequate response to prednisolone, propranolol, and vincristine. He had a prompt positive clinical and laboratory response to sirolimus, but 4 weeks after starting it, at the age of 4 months, he developed PCP. This led to respiratory failure, which required extracorporeal membrane oxygenation. Sirolimus was temporarily discontinued, and he was successfully treated for PCP with sulfamethoxazole-trimethoprim and methylprednisolone. He was restarted on sirolimus 3 weeks after discharge and given sulfamethoxazole-trimethoprim prophylaxis. At the age of 22 months, while still on sirolimus, the lesion continued to improve with test results revealing stable hemoglobin and platelet counts. PCP is a rare but life-threatening side effect of sirolimus therapy, especially in the setting of concurrent steroid treatment. prophylaxis should be considered for patients receiving sirolimus.

Acupressure bands were safe but did not improve chemotherapy-induced nausea or vomiting in pediatric patients who were receiving highly emetic chemotherapy. Cancer 2018;124:1188-96. © 2017 American Cancer Society.

ABSTRACT. Objective. The varicella-zoster virus (VZV) continues to be a dangerous pathogen to immunocompromised children. Children with acute lymphoblastic leukemia (ALL) are treated with intermittent steroid therapy. This study was undertaken to examine the relationship between steroid therapy for ALL and severity of varicella infection.Methods. We performed a retrospective review of patients who were on Pediatric Oncology Group Protocol 9201 and had a history of varicella infection. Pediatric Oncology Group 9201 is a phase III study for the treatment of children with lesser risk ALL diagnosed between 1992 and 1999. Cases of varicella were coded 1 to 5 on the basis of severity: grade 1 caused minimal to no symptoms, grade 2 caused mild to moderate symptoms that did not require hospitalization, grade 3 caused symptoms severe enough to require hospitalization and intravenous acyclovir, grade 4 caused severe disease that had complications or that required intensive care, and grade 5 resulted in death.Results. Of 697 enrolled patients, 110 (15.8%) developed primary varicella; 59% of these were male. For analysis, disease grade was dichotomized into nonsevere (grades 1 and 2) and severe (grades 3, 4, and 5). Of the 110 patients, 56 had nonsevere disease; 54 had severe disease, including 2 deaths. Of the patients whose varicella was diagnosed within 3 weeks of receipt of prednisone, 70% had severe infection, whereas only 44% of those who had not received prednisone within 3 weeks had severe infection. The odds ratio for having a severe infection within 3 weeks of prednisone versus >3 weeks is 2.9 (95% confidence interval: 1.1-7.9). By multivariate analysis, older age at ALL diagnosis, years from ALL diagnosis to VZV diagnosis, and VZV diagnosis within the 4-week period of interest (during or within 3 weeks of prednisone therapy) all were independently associated with an increased risk for severe infection.Conclusions. This study represents the largest study to date of varicella in children with ALL and provides convincing evidence that prednisone therapy during the VZV incubation period significantly increases the risk for developing severe varicella infection. In addition, older age is associated with more severe infection. Despite the varicella vaccine and a dropping incidence of primary infections, VZV remains a dangerous pathogen for pediatric patients with ALL. With the possible exception of induction therapy, patients who are on ALL therapy and are exposed to varicella should have steroid therapy delayed until after the VZV incubation period. T he varicella-zoster virus (VZV) is well recognized as a potential cause of morbidity and mortality in immunocompromised children. Small series and case reports in children have noted an association between steroid therapy and severe VZV infections. [1][2][3][4][5][6][7][8] In children with acute lymphoblastic leukemia (ALL), steroid therapy and its relation to VZV severity have not been well studied. We hypothesized that patients who received recent (within 3 weeks) ster...