Melanie Comito

Intensive chemotherapy followed by consolidative myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) in young children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNETs): report of the Head Start I and II experience.

Children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNET) have poor outcomes compared to medulloblastoma patients, despite similar treatments. In an effort to improve overall survival (OS) and event‐free survival (EFS) and to decrease radiation exposure, the Head Start (HS) protocols treated children with newly diagnosed sPNET utilizing intensified induction chemotherapy (ICHT) followed by consolidation with myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR).

A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer

Preclinical models show that an antiangiogenic regimen at low‐dose daily (metronomic) dosing may be effective against chemotherapy‐resistant tumors. We undertook a prospective, open‐label, single‐arm, multi‐institutional phase II study to evaluate the efficacy of a “5‐drug” oral regimen in children with recurrent or progressive cancer.

Feasibility and parent satisfaction of a physical therapy intervention program for children with acute lymphoblastic leukemia in the first 6 months of medical treatment

Children with acute lymphoblastic leukemia (ALL) are at risk for developing musculoskeletal complications during and after their medical treatment. The objective of this study was to examine the feasibility of an in‐hospital physical therapy‐ and home exercise program during the first four phases of medical treatment, for children with newly diagnosed ALL.

Epstein Barr virus induced lymphoma in a child with IPEX syndrome.

IPEX syndrome (immune deficiency, polyendocrinopathy, enteropathy, X‐linked) is a disorder or regulatory T cell (Treg) function which can result in early death due to infection or complications related to autoimmunity. Therapeutic options for these patients can include allogeneic stem cell transplantation (SCT) or the use of immunosuppressive regimens to control the manifestations of autoimmunity. We report a patient with IPEX syndrome who was managed with rapamycin and subsequently developed EBV induced lymphoma. Pediatr Blood Cancer 2008;50:1056–1057.

Immunotherapy for Epstein – Barr Virus-Associated Tumors

Epstein-Barr Virus (EBV) is associated with a number of tumors, including lymphomas in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, patients with the acquired immunodeficiency syndrome (AIDS), Burkitts lymphoma, as well as a subset of patients with nasopharyngeal carcinoma (NPC) and Hodgkins disease (HD). The types of latent EBV infections vary in these tumors, which influences the EBV antigens expressed and ultimately the immunogenicity of tumor cells. Not all EBV associated malignancies are directly related to altered cellular immunity, as is the case with EBV induced lymphoproliferations in immunocompromised patients. Treatment strategies have ranged from restoration of normal cellular immunity, which is generally successful in SOT and HSCT patients, anti-B cell monoclonal antibodies, and conventional chemotherapy and radiation. The fact that these tumors express EBV antigens for which many individuals have high circulating levels of protective cytotoxic T lymphocytes (CTL) has lead to investigation into the applicability of adoptive transfer of EBV specific T cells. Initial success with adoptive immunotherapy for HSCT and SOT patients has lead to current studies examining the feasibility and efficacy of this strategy for other EBV associated tumors, such as NPC and HD. We will review the pathogenesis of these disorders, current therapies, and future investigations aimed at targeting EBV antigen expression on these tumors.

Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma (DIPG): A Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.

Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma

Background Diagnosis of diffuse intrinsic pontine glioma (DIPG) has relied on imaging studies, since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets. Methods Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG. Surgical biopsies were performed after enrollment and prior to definitive treatment. All subjects were treated with conventional external beam radiotherapy with bevacizumab, and then stratified to receive bevacizumab with erlotinib or temozolomide, both agents, or neither agent, based on O6-methylguanine-DNA methyltransferase status and epidermal growth factor receptor expression. Whole-genome sequencing and RNA sequencing were performed but not used for treatment assignment. Results Fifty-three patients were enrolled at 23 institutions, and 50 underwent biopsy. The median age was 6.4 years, with 24 male and 29 female subjects. Surgical biopsies were performed with a specified technique and no deaths were attributed to the procedure. Two subjects experienced grade 3 toxicities during the procedure (apnea, n = 1; hypertension, n = 1). One subject experienced a neurologic deficit (left hemiparesis) that did not fully recover. Of the 50 tumors biopsied, 46 provided sufficient tissue to perform the study assays (92%, two-stage exact binomial 90% CI: 83%-97%). Conclusions Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that can inform treatment decisions.