Leukemia is the most common childhood cancer and a major source of morbidity and mortality. The etiology of childhood leukemia remains largely unknown. Cytogenetic abnormalities determine disease subtypes, prognosis, clinical presentation, and course and may help in discovering etiological factors. Epidemiologic investigations of leukemia are complicated by many factors, including the rarity of the disease, necessitating careful study design. Two emerging areas of interest in leukemia etiology are birth weight and diet. High birth weight has been associated with increased risk of childhood leukemia. The biological mechanism behind this association may involve insulin-like growth factor I (IGF-I), which is associated with high birth weight. IGF-I may act by increasing the absolute number of stem cells available for transformation, stimulating the growth of cells that are already transformed, or a combination of effects. Diet has been linked with leukemia. Maternal dietary DNA topoisomerase II (DNAt2) inhibitor intake is associated with infant acute myeloid leukemia (AML) with the MLL gene translocation. Increased intake of fruits and vegetables has been associated with decreased leukemia risk and, relatedly, lack of maternal folate supplementation has been associated with increased childhood leukemia risk, possibly by causing DNA hypomethylation and increased DNA strand breaks. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms modify this risk.

BackgroundThe mixed lineage leukemia (MLL) gene is commonly rearranged in infant leukemia (IL). Genetic determinants of susceptibility to IL are unknown. Recent genome‐wide association studies for childhood acute lymphoblastic leukemia (ALL) have identified susceptibility loci at IKZF1, ARID5B, and CEBPE.ProcedureWe genotyped these loci in 171 infants with leukemia and 384 controls and evaluated associations overall, by subtype [ALL, acute myeloid leukemia (AML)], and by presence (+) or absence (−) of MLL rearrangements.ResultsHomozygosity for a variant IKZF1 allele (rs11978267) increased risk of infant AML [Odds ratio (OR) = 3.9, 95% confidence interval (CI) = 1.8–8.4]; the increased risk was similar for AML/MLL+ and MLL− cases. In contrast, risk of ALL/MLL− was increased in infants homozygous for the IKZF1 variant (OR = 5.1, 95% CI = 1.8–14.5) but the variant did not modify risk of ALL/MLL+. For ARID5B (rs10821936), homozygosity for the variant allele increased risk for the ALL/MLL− subgroup only (OR = 7.2, 95% CI = 2.5–20.6). There was little evidence of an association with the CEBP variant (rs2239633).ConclusionIKZF1 is expressed in early hematopoiesis, including precursor myeloid cells. Our data provide the first evidence that IKZF1 modifies susceptibility to infant AML, irrespective of MLL rearrangements, and could provide important new etiologic insights into this rare and heterogeneous hematopoietic malignancy. Pediatr Blood Cancer 2013; 60: 31–34. © 2012 Wiley Periodicals, Inc.

IMPORTANCEOlmsted syndrome is a rare and disabling genodermatosis for which no successful treatment is currently available. OBJECTIVE To evaluate the clinical response to the mammalian target of rapamycin (mTOR) inhibitor sirolimus and/or the epidermal growth factor receptor (EGFR) inhibitor erlotinib among patients with Olmsted syndrome. DESIGN, SETTING, AND PARTICIPANTSThis case series focused on 4 children with treatment-refractory Olmsted syndrome. These children received treatments (initiated in 2017 and 2018) at the outpatient dermatology clinic at the Children'

Anthracycline induced cardiotoxicity remains a significant contributor to late morbidity/mortality in children and young adults with acute myeloid leukemia (AML). The cardioprotectant dexrazoxane can be used as prophylaxis to diminish risk for cardiomyopathy but whether it affects risk of relapse in pediatric AML is unclear. Our institution adopted the use of dexrazoxane prior to anthracyclines administration for all oncology patients in 2011. We compared patients with AML (ages 0 to 21 years) who received or did not receive dexrazoxane during the years 2008 to 2013. Forty-four patients with AML (ages 4.5 months to 21.7 years) were included. We identified no statistical difference in 2-year event rate (62% vs. 50%, p=0.41) or 2-year overall survival (OS) (69% vs. 69%, p=0.53) between patients receiving (n=28) or not receiving (n=16) dexrazoxane. Ejection fraction (p=0.0262) and shortening fraction (p=0.0381) trended significantly higher in patients that received dexrazoxane compared to those that did not receive dexrazoxane. Utilization of the cardioprotectant dexrazoxane prior to anthracycline chemotherapy in pediatric patients with AML demonstrated no significant difference in either event rate or OS relative to institutional controls and appears to improve cardiac function indices. Further studies in this patient population are needed to confirm these findings.

A 9-year-old female presented with a large abdominal mass. At surgery, the mass was noted to arise from the right adrenal gland. As the mass was manipulated, the patient developed severe hypertension. The final diagnosis was a cystic composite-pheochromocytoma/ganglioneuroblastoma. This compound adrenal tumor is only the fourth case reported in a child. Because composite pheochromocytomas are rare in the pediatric population, the management, optimal surveillance schedule and outcomes have not been characterized.