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Journal: Pediatric blood & cancer


Cisplatin may cause permanent cochlear damage by changing cochlear frequency selectivity and can lead to irreversible sensorineural hearing loss. High-frequency audiometry (HFA) is able to assess hearing frequencies above 8,000 Hz; hence, it has been considered a high-quality method to monitor and diagnose early and asymptomatic signs of ototoxicity in patients receiving cisplatin.

Concepts: Cochlear implant, Ototoxicity, Otology, Hertz, Ear, Tinnitus, Sensorineural hearing loss, Audiogram


Hemophilia A and hemophilia B are caused by congenital deficiency of factor VIII and factor IX, respectively, and may lead to recurrent, spontaneous bleeding into the muscles and joints resulting in disabling arthropathy. Effective management is available in the form of prophylactic infusions of clotting factor concentrates which have been demonstrated to prevent bleeding episodes and greatly improve the quality of life of these patients. Prophylaxis is, however, expensive. Usual dosing regimens rely on weight based calculations but dosing with an understanding of an individual’s pharmacokinetic response has been demonstrated to be more effective in predicting clotting factor levels that protect against bleeding episodes. Standard pharmacokinetic studies require a prohibitive number of time sampling points but recent population or Bayesian pharmacokinetics can be used to provide an accurate estimation of an individual’s pharmacokinetic response using a limited number of sampling time points. The use of population pharmacokinetics has the potential to greatly increase the use of pharmacokinetic dosing regimens and optimize the use of clotting factor concentrates in patients with hemophilia. Pediatr Blood Cancer 2012; 60: S27-S29. © 2012 Wiley Periodicals, Inc.

Concepts: Blood, Coagulation, Pharmacokinetics, Haemophilia A, Haemophilia B, Factor X, Coagulation system, Factor IX


Renal malignancies are among the most prevalent pediatric cancers. The most common is favorable histology Wilms tumor (FHWT), which has 5-year overall survival exceeding 90%. Other pediatric renal malignancies, including anaplastic Wilms tumor, clear cell sarcoma, malignant rhabdoid tumor, and renal cell carcinoma, have less favorable outcomes. Recent clinical trials have identified gain of chromosome 1q as a prognostic marker for FHWT. Upcoming studies will evaluate therapy adjustments based on this and other novel biomarkers. For high-risk renal tumors, new treatment regimens will incorporate biological therapies. A research blueprint, viewed from the perspective of the Children’s Oncology Group, is presented. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.

Concepts: Medicine, Cancer, Oncology, Lung cancer, Types of cancer, Tumor, Malignancy, Wilms' tumor


BACKGROUND: Growth differentiation factor 15 (GDF15), a divergent TGFβ superfamily, has recently been implicated in the modulation of iron homeostasis, acting as an upstream negative regulator of hepcidin, the key iron regulatory hormone produced primarily by hepatocytes. However, little is known about possible roles that GDF15 might play in the regulation of iron homeostasis and development of hyperferritinemia in children with hemophagocytic lymphohistiocytosis (HLH). PROCEDURES: We compared serum GDF15 level and mRNA expressions of GDF15 and key molecules of iron metabolism, and made correlations between their expressions in children with HLH and control children. RESULTS: Serum GDF15 level was remarkably higher in HLH group than that in controls, with median serum concentration of 1,700 and 260 pg/ml, respectively (P < 0.001). In addition, GDF15 mRNA was significantly upregulated but independent of hypoxia-inducible factor-mediated oxygen signaling pathway. More importantly, GDF15 induction was positively correlated to upregulation of ferroportin, the only cellular iron exporter, and to upregulation of ferritin heavy chain. CONCLUSIONS: Our study suggests that GDF15 induction helps suppress further activation of macrophages in stressful physiologic states as HLH, and is intimately implicated in the development of hyperferritinemia by modulating the hepcidin-ferroportin axis, resulting in enhanced ferroportin-mediated iron efflux. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

Concepts: Gene expression, Regulation of gene expression, Hematology, Iron deficiency anemia, Human iron metabolism, Anemia of chronic disease, Ferroportin, Hepcidin


Children presenting with medulloblastoma have a wide range of initial presenting symptoms. However, the influence of underlying tumor biology on the initial presentation of medulloblastoma is currently unknown. In light of the recent discovery of distinct medulloblastoma subgroups, we sought to define the initial presentation of childhood medulloblastoma in a subgroup specific manner.


Constitutional mismatch repair deficiency (CMMRD) is a cancer predisposition syndrome associated with a high risk of developing early-onset malignancies of the blood, brain, and intestinal tract. We present the case of a patient with T-lymphoblastic lymphoma at the age of 3 years, followed by Burkitt lymphoma 10 years later. This patient also exhibited numerous nonmalignant findings including café au lait spots, lipomas, bilateral renal nodules, a nonossifying fibroma, multiple colonic adenomas, and a rapidly enlarging pilomatrixoma. The spectrum of malignant and nonmalignant neoplasms in this patient highlights the remarkable diversity, and early onset, of lesions seen in children with CMMRD.

Concepts: AIDS, Cancer, Oncology, Anatomical pathology, Types of cancer, Benign tumor, Fibroma, Nonossifying fibroma


Antibiotic delivery to patients with fever and neutropenia (F&N) in <60 min is an increasingly important quality measure for oncology centers, but several published reports indicate that a time to antibiotic delivery (TTA) of <60 min is quite difficult to achieve. Here we report a quality improvement (QI) effort that sought to decrease TTA and assess associated clinical outcomes in pediatric patients with cancer and F&N.

Concepts: Medicine, Cancer, Oncology, Antibiotic resistance, Chemotherapy, Report, Antibiotic


The impact of ambulatory bloodstream infections (Amb-BSIs) in pediatric oncology and stem cell transplant (PO/SCT) patients is poorly understood, although a large portion of their treatment increasingly occurs in this setting. This study aimed to understand the economic impact and length of stay (LOS) associated with these infections.

Concepts: Health care, Health care provider, Medicine, Oncology, Understanding, Chemotherapy, Illness, Specialty


Infantile fibrosarcoma (IFS) is a rare pediatric cancer typically presenting in the first 2 years of life. Surgical resection is usually curative and chemotherapy is active against gross residual disease. However, when recurrences occur, therapeutic options are limited. We report a case of refractory IFS with constitutive activation of the tropomyosin-related kinase (TRK) signaling pathway from an ETS variant gene 6-neurotrophin 3 receptor gene (ETV6-NTRK3) gene fusion. The patient enrolled in a pediatric Phase 1 trial of LOXO-101, an experimental, highly selective inhibitor of TRK. The patient experienced a rapid, radiographic response, demonstrating the potential for LOXO-101 to provide benefit for IFS harboring NTRK gene fusions.

Concepts: Immune system, Protein, Medicine, Gene expression, Cancer, Signal transduction, Life, Physician


Poverty is correlated with negative health outcomes in pediatric primary care, and is emerging as a negative prognostic indicator in pediatric oncology. However, measures of poverty amenable to targeted intervention, such as household material hardship (HMH)-including food, energy, and housing insecurity-have not been described in pediatric oncology. We describe the trajectory of family reported HMH and income poverty at a pediatric oncology referral center in New England with high psychosocial supports.

Concepts: Family, Medicine, Cancer, Oncology, Chemotherapy, Specialty