Utilization of Thiopurine Metabolites and Allopurinol in Pediatric Acute Lymphoblastic Leukemia: Consideration for an Algorithmic Approach.

Persistently elevated absolute neutrophil counts during maintenance for acute lymphoblastic leukemia is a risk factor for relapse and may be related to wild-type thiopurine methyltransferase activity and overly efficient shunting of 6-mercaptopurine to hepatotoxic metabolites (6-methylmercaptopurine nucleotides), leading to low 6-thioguanine nucleotides. 6-mercaptopurine is also metabolized by xanthine oxidase, and therefore allopurinol, an inhibitor of xanthine oxidase, allows for increased 6-thioguanine nucleotides and decreased 6-methylmercaptopurine nucleotide. Here, we report our experience with allopurinol for persistently elevated absolute neutrophil count or hepatotoxicity and suggest an algorithmic approach for checking thiopurine metabolites and initiating allopurinol in acute lymphoblastic leukemia maintenance.

The genetic landscape of gliomas arising after therapeutic radiation.

Radiotherapy improves survival for common childhood cancers such as medulloblastoma, leukemia, and germ cell tumors. Unfortunately, long-term survivors suffer sequelae that can include secondary neoplasia. Gliomas are common secondary neoplasms after cranial or craniospinal radiation, most often manifesting as high-grade astrocytomas with poor clinical outcomes.

The genetic landscape of ganglioglioma.

Ganglioglioma is the most common epilepsy-associated neoplasm that accounts for approximately 2% of all primary brain tumors. While a subset of gangliogliomas are known to harbor the activating p.V600E mutation in the BRAF oncogene, the genetic alterations responsible for the remainder are largely unknown, as is the spectrum of any additional cooperating gene mutations or copy number alterations.

Large Vessel Arteriopathy After Cranial Radiation Therapy in Pediatric Brain Tumor Survivors.

Among childhood cancer survivors, increased stroke risk after cranial radiation therapy may be caused by radiation-induced arteriopathy, but limited data exist to support this hypothesis. Herein, we assess the timing and presence of cerebral arteriopathy identified by magnetic resonance angiography (MRA) after cranial radiation therapy in childhood brain tumor survivors. In a cohort of 115 pediatric brain tumor survivors, we performed chart abstraction and prospective annual follow-up to assess the presence of large vessel cerebral arteriopathy by MRA.

Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy.

Background: Molecular profiling is revolutionizing cancer diagnostics and leading to personalized therapeutic approaches. Herein we describe our clinical experience performing targeted sequencing for 31 pediatric neuro-oncology patients.

Methods: We sequenced 510 cancer-associated genes from tumor and peripheral blood to identify germline and somatic mutations, structural variants, and copy number changes.

Survival after chemotherapy and stem cell transplant followed by delayed craniospinal irradiation is comparable to upfront craniospinal irradiation in pediatric embryonal brain tumor patients.

Pediatric embryonal brain tumor patients treated with craniospinal irradiation (CSI) are at risk for adverse effects, with greater severity in younger patients. Here we compare outcomes of CSI vs. high-dose chemotherapy (HD), stem cell transplant (SCT) and delayed CSI in newly diagnosed patients.

Presence of cerebral microbleeds is associated with worse executive function in pediatric brain tumor survivors.

Background: A specific form of small-vessel vasculopathy-cerebral microbleeds (CMBs)-has been linked to various types of dementia in adults. We assessed the incidence of CMBs and their association with neurocognitive function in pediatric brain tumor survivors.

Methods: In a multi-institutional cohort of 149 pediatric brain tumor patients who received cranial radiation therapy (CRT) between 1987 and 2014 at age <21 years and 16 patients who did not receive CRT, we determined the presence of CMBs on brain MRIs.

Outcome of young children with high-grade glioma treated with irradiation-avoiding intensive chemotherapy regimens: Final report of the Head Start II and III trials.

Purpose: To report the final analysis of survival outcomes for children with newly diagnosed high-grade glioma (HGG) treated on the "Head Start" (HS) II and III protocols with chemotherapy and intent to avoid irradiation in children <6 years old.

Patients And Methods: Between 1997 and 2009, 32 eligible children were enrolled in HS II and III with anaplastic astrocytoma (AA, n = 19), glioblastoma multiforme (GBM, n = 11), or other HGG (n = 2). Central pathology review was completed on 78% of patients.

Intensive induction chemotherapy followed by myeloablative chemotherapy with autologous hematopoietic progenitor cell rescue for young children newly-diagnosed with central nervous system atypical teratoid/rhabdoid tumors: the Head Start III experience.

Background: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS) is a rare embryonal neoplasm of early childhood with dismal outcome and no current uniformly accepted treatment. Given its highly aggressive nature and predilection for dissemination at diagnosis, intensive multimodal therapy is required.

Materials And Methods: Nineteen children with newly diagnosed CNS AT/RT were treated on the head start (HS) III protocol.