Lymphoma Drug Approval, Fetal Therapy, NTRK Fusions, Infection Control at COVID Care Site, Epilepsy and Autism, Gift Supports Pediatric Brain Tumor Research

shafere1 [at] chop.edu (By Emily Shafer)

In this week's news roundup, Pfizer approves a drug for anaplastic large cell lymphoma, based on data from a study led by CHOP. Learn about a new method to deliver mRNA as fetal therapy, the role of NTRK fusions in pediatric cancers, and an infection control program implemented at a COVID-19 alternate care site. Find out how epilepsy and autism may be genetically linked. Lastly, the Children's Brain Tumor Network receives a gift to accelerate open science to improve health for all children and young adults diagnosed with a brain tumor.

Pfizer Approves Drug for Anaplastic Large Cell Lymphoma

The FDA approved Pfizer's crizotinib for ALK-fusion positive relapsed/refractory anaplastic large cell lymphoma (ALCL), based on a pivotal study led by researchers at Children's Hospital of Philadelphia through the Children's Oncology Group (COG).

Crizotinib (brand name Xalkori) is a first generation ALK inhibitor. Approximately 90 percent of pediatric ALCL cases are ALK-positive. Yael P. Mossé, MD, attending physician in CHOP's Cancer Center and associate professor of Pediatrics at Perelman School of Medicine at the University of Pennyslvania, was the principal investigator for the study. She has previously studied ALK alterations in several cancers.

The approval of Xalkori marks an important moment for pediatric patients with ALK-positive ALCL who suffer a relapse during or after standard upfront chemotherapy, and who now have another treatment option that may one day prove to be an integral component of curative therapy, Dr. Mossé said. This is a big step forward and one that will give hope to many patients and families.

Learn more about the approval and the study on CHOP News.

Nanoparticles Could Deliver mRNA in Fetal Therapy

Researchers at CHOP and the School of Engineering and Applied Science at the University of Pennsylvania identified ionizable lipid nanoparticles that could be used to deliver mRNA as part of fetal therapy. The study, which appeared in Science Advances, laid the groundwork to test potential therapies for treating genetic diseases before birth.

This is an important first step in identifying nonviral mediated approaches for delivering cutting-edge therapies before birth, said co-senior author William H. Peranteau, MD, attending surgeon in the Division of General, Thoracic and Fetal Surgery, and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at CHOP. These lipid nanoparticles may provide a platform for in utero mRNA delivery, which could be used in therapies like fetal protein replacement and gene editing.

The study team engineered a library of lipid nanoparticles that effectively enter cells in mouse models. They found that several of the lipid nanoparticles enabled functional mRNA delivery to fetal livers, and some also allowed functional mRNA delivery to the fetal lungs and intestines. The lipid nanoparticles were as safe as or safer than existing formulations.

Michael J. Mitchell, PhD, Skirkanich Assistant Professor of Innovation in Penn Engineering's Department of Bioengineering, is the other co-senior author of the study. To learn more about the findings, check out the CHOP press release.

NTRK Fusions More Common in Pediatric Cancers Than Expected

Neurotrophic tyrosine receptor kinase (NTRK) fusions, a biomarker used to identify pediatric cancer patients suitable for treatment with TRK inhibitors, are more common than previously thought, according to researchers from CHOP. The findings appeared in JCO Precision Oncology.

Our findings demonstrate that NTRK fusions are far more frequently seen in pediatric tumors than in adult tumors and involve a broader panel of fusion partners and a wider range of pediatric tumors than previously recognized, said senior author Marilyn M. Li, MD, vice chief of the Division of Genomic Diagnostics and director of Cancer Genomic Diagnostics at CHOP. With the recent FDA approval of larotrectinib and entrectinib for the treatment of adult and pediatric NTRK-positive, unresectable solid tumors, identification of these fusions directly impacts patient care.

Dr. Li and her team analyzed 1,347 consecutive pediatric tumors from 1,217 patients who underwent tumor genomic profiling. They identified NTRK fusions in 29 tumors from 27 patients. During 46 months of follow-up, the detection of an NTRK fusion confirmed the diagnosis of the lesion type in almost all cases.

Learn more about the study in the CHOP press release.

Article Highlights Implementing Infection Control Program at Alternate Care Site

A new article that appeared in American Journal of Infection Control highlighted the experience of planning, executing, and evaluating infection prevention and control (IPC) standards at an alternate care site (ACS) established to treat low-acuity COVID-19 patients.

Susan Coffin, MD, MPH, professor of Pediatrics in the Division of Infectious Diseases at CHOP, was part of the study, in her role with the Philadelphia Department of Health. Dr. Coffin and colleagues evaluated an IPC program of an ACS set up at Temple University as an overflow medical facility for patients with COVID-19.

The IPC team, led by a doctor and nurse partnership, trained 425 staff in IPC practices and personal protective equipment standards. The team also created systems to detect staff illness. The team used existing guidance from a conceptual model called the 4S's: Space, Staff, Stuff, and Systems.

The IPC team worked quickly and efficiently to manage the constantly evolving circumstances and the time constraints that accompanied the opening of a COVID-19 pandemic ACS, the researchers wrote.

Autism, Epilepsy May Share Genetic Pathways

In a new study appearing in Scientific Reports, researchers from CHOP highlight the genetic pathways shared by epilepsy and autism spectrum disorder, two heterogeneous brain disorders. The findings warrant further exploration, which could yield better treatments for both conditions.

The researchers created an integrated network, layering information about clinical presentation with data regarding traditional protein-protein interactions, to determine which genes and biological pathways were specific to ASD and epilepsy, and which were shared. They were able to sub-cluster the patients with ASD and epilepsy into subgroups that share similar phenotypes and likely, similar genetic pathways.

Understanding the genetic connection of epilepsy and autism can aid in the discovery and prioritization of candidate genes for either disorder and the understanding of their shared molecular pathophysiology, said senior author Kai Wang, PhD, associate professor of Pathology and Laboratory Medicine at CHOP. Given that many neurological disorders have a common genetic etiology, other neurological disorders like depression, anxiety, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder should also be explored in relation to epilepsy and autism, using this approach of an integrated, multiplex network.

Find out more about the study in the CHOP press release.

Philanthropic Funding Support Children's Brain Tumor Network's Research

A charitable gift from the Swifty Foundation will support the Children's Brain Tumor Network to accelerate the pace of translational research and the discovery of new treatments, with the goal of saving children and young adults from brain tumors.

The Swifty Foundation philanthropic funding enables CBTN to expand its operations staff through the creation of new roles, all working toward finding cures for pediatric brain cancer. At present, CBTN maintains over 45,000 biospecimens, paired with over 400TB of associated data, accessible through a collection of cloud-based analysis platforms that are interoperable across a broad spectrum of NIH data commons.

The organization has also supported more than 600 global researchers in launching over 170 research projects. It has collaborated with a number of global research organizations, including the Pacific Pediatric Neuro-Oncology Consortium, for whom CBTN supports real-time clinical trial data integration.

The Center for Data Driven Discovery in Biomedicine (D3b) at CHOP acts as the Operations Center for the CBTN.

See the CBTN press release for more details.

ICYMI

Catch up on our headlines from our Jan. 8 In the News:

• Outcome Disparities Found in Children With Severe Sepsis in United States
• Study Shows No Difference Between Higher and Lower Hemoglobin Strategies for Extremely Small Babies
• Adolescent Drivers Return to the Road Within Two Weeks Post-Concussion
• Human Cell Models Developed to Study Beckwith-Wiedemann Syndrome Disease Development

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