Rose Bowl Parade, Asthma, Cardiac Imaging, Pediatric Leukemia, Immune Response

The end of the year has come up fast, and so have important advances in pediatric research at Children’s Hospital of Philadelphia. This week’s In the News starts off with a celebration of two remarkable patients and their dedicated pediatric oncologist.

Riding Into the New Year to Raise Cancer Research Awareness

Time has flown since our initial In the News report that Yael Mossé, MD, a CHOP pediatric oncologist and physician-scientist specializing in neuroblastoma, will ride into 2017 in style with two special patients on a Rose Bowl parade float Jan. 2. The theme of the 128th Rose Parade in Pasadena, Calif., is "Echoes of Success," honoring selfless contributions by inspirational figures.

Dr. Mossé told Philly.com that she’s a little nervous about her appearance: “This is a unique experience for me,” Dr. Mossé said. “I prefer to stay under the radar. It’s where I do my best work.”

But we know that Dr. Mossé will shine along with her patients, 7-year-old Edie Gilger and her mother, Emily Gilger, who are in remission after battling neuroblastoma. Dr. Mossé developed their treatment after identifying a genetic mutation that is a driver of most cases of rare, inherited neuroblastoma.

They will travel the parade route on the Northwestern Mutual float, "Waves of Hope." Northwestern Mutual contributes funding to Dr. Mossé’s research at CHOP. Read more about her work here.

New Study Analyzes Patients With Asthma at Ground Level

Home visits offer a fuller understanding of how the social environment of asthma patients impacts their overall health, according to a CHOP research team. They analyzed reports from community health workers who meet with asthma patients at home, where extreme living conditions such as poor housing, neighborhood violence, and lack of social support impose steep barriers to public healthcare, as well as to high-quality research.

Researchers from the Community Asthma Prevention Program (CAPP) at CHOP and the Perelman School of Medicine at the University of Pennsylvania described those challenges in a study in the Journal of Allergy and Clinical Immunology. The authors focused on 301 adults living in low-income Philadelphia neighborhoods who were prescribed an inhaled corticosteroid for asthma and required oral steroids for an exacerbation and/or had an emergency or inpatient visit within the last six months.

They found 71 percent rented, with many living in one-room apartments or overcrowded spaces with multiple family members, and they were routinely exposed to common indoor asthma triggers, such as rodents, roaches, and mold. Only 25 percent of people who participated in the study were currently employed either part or full-time. Other issues community health workers encountered were low education rates, limited access to healthy foods, and poor general health.

"Many of these patients start to feel a sense of hopelessness, especially the very sick," said Tyra Bryant-Stephens, MD, corresponding author and medical director of CAPP at CHOP. "They feel there is very little possibility of changing their current living situation, which includes poor housing, exposure to violent crime, and limited access to transportation. Some of these living conditions make it difficult or impossible for patients to get to their medical visits, which results in a further decline of their health."

Read more in this press release.

Cardiac Experts Study Imaging Tool to Improve Open Heart Surgeries

Pediatric cardiology experts at CHOP suggest that echo imaging, called transesophageal echocardiography (TEE), during surgery may improve outcomes for children with congenital heart disease. The scientists reported on the use of intraoperative TEE to identify intramural ventricular septal defects (VSDs) — holes in the wall between two heart chambers.

“These defects, which can occur after initial surgery for another defect, can increase the risk of complications and mortality in children with heart disease, so using imaging tools to quickly identify these defects can improve our care of these children,” said Meryl S. Cohen, MD, senior author and pediatric cardiologist at CHOP. She and co-authors previously published a paper that recognized these defects as being distinct from other types of residual holes.

The current study was the first to assess the accuracy of TEE in identifying intramural VSDs. The study team compared intraoperative TEE, which was performed during surgery, to another imaging tool, transthoracic echocardiography (TTE), done after surgery. Of the 337 surgical patients, 34 had intramural VSDs. Of those 34, both TTE and TEE identified 19 VSDs, while 15 were identified by TTE only. That data showed that TEE had modest sensitivity (56 percent), but high specificity (100 percent) in identifying intramural VSDs.

“We hope that this research will increase clinicians’ awareness of these intramural defects as an important distinct entity related to surgical complications,” said the study’s first author, Jyoti K. Patel, MD, a former cardiac fellow in the Cardiac Center at CHOP who conducted the research during her fellowship. “If a greater awareness enhances the use of TEE in the operating room, surgeons may better develop strategies to both help prevent these lesions and to consider revising their operations before the patient leaves the operating room if an intramural VSD exists.”

The study team published the research in the Journal of Thoracic and Cardiovascular Surgery. Read more in this press release.

Patient Story Highlights Experimental Pediatric Leukemia Therapy

In a recent Philly.com article, we met 15-year-old Emma Collins, a patient with leukemia who traveled to CHOP from Ontario, Canada, to try an investigational immunotherapy. The personalized treatment modifies a patient’s own immune T cells, extracted and engineered to potentially seek and destroy the patient’s leukemia cells.

CHOP pediatric oncologist Stephan Grupp, MD, director of CHOP’s Cancer Immunotherapy Frontier Program, reported results from the first global, multicenter trial (ELIANA) of the T-cell treatment known as chimeric antigen receptor (CAR) T cells, or CTL019 cells, of which he is the lead investigator. Among the 50 patients who have received a single dose of the T cells, 41 patients (82 percent) had a complete response (that is, no detectable leukemia cells) within one to three months after treatment.

ELIANA is sponsored by Novartis, which aims to apply for U.S. Food and Drug Administration approval in 2017. The research reflects an ongoing collaboration between Dr. Grupp, his Penn colleagues led by Carl H. June, MD, and Novartis.

As in previous, single-center trials, the immunotherapy stimulated a sometimes severe side effect called cytokine release syndrome (CRS), a known complication of the investigational therapy that may occur when the engineered cells become activated in the patient’s body. Some patients require anti-immune drugs and intensive care, as Emma did following her second T-cell infusion.

A year after her treatment at CHOP, Emma remains in remission and is a promising young athlete. Her family is hopeful that other children around the world may one day benefit from CTL019 therapy.

The prospect of having the world's first approved T-cell immunotherapy "is the most exciting thing I’ve been involved with in my life as a scientist, and especially as a clinician," Dr. Grupp told Philly.com

Researchers Reveal Signaling Circuits Involved in Immune Responses

Using bioinformatics tools to identify and map out specific components and regulatory interconnections, a study team from CHOP and the University of Iowa identified biological pathways that come into play when CD8⁺ T cells mount an immune response.

The researchers investigated a distinct repertoire of super enhancers, which drive expression of genes to carry out biological processes, that are highly dynamic during three stages of CD8⁺ T cells’ development. CD8⁺ T cells begin in a naïve pre-infected state. When they encounter an antigen, they differentiate into large quantities of effector cells to clear an infection. After the infection, cell numbers diminish, but central memory T cells retain a long-term ability to defend against reinfection by microorganisms that carry the same antigen.

“Better understanding of these mechanisms is important because increasing the quantity and quality of memory CD8⁺ T cells is a key goal in developing more effective vaccines and immunotherapeutic strategies,” said study co-leader Kai Tan, PhD, of the Center for Childhood Cancer Research and the departments of Pediatrics and Biomedical and Health Informatics at CHOP. “In addition, although many shared properties exist between infection and cancer, future studies identifying distinct regulatory wiring in cancer-infiltrating T cells are essential for the continued progress of cancer immunotherapy.”

Dr. Tan and colleagues at CHOP co-authored the study with a team led by Hai-Hui Xue, MD, PhD, of the Carver College of Medicine at the University of Iowa. The research appeared online in Immunity. Read more in the press release.

ICYMI

In case you missed it, this week on Cornerstone we highlight a selection of 2016 stories that give a small glimpse into how much smart scientists, committed healthcare providers, dedicated families, and other supporters, can achieve together in advancing the discovery of better ways to help more children grow up healthy and strong.

Our Dec. 16 In the News post shared the latest findings reported by CHOP researchers at The American Society of Hematology (ASH) annual, described new PolicyLab research that raises concerns about Army-reported rates of child abuse, introduced CHOP’s new Radiologist in Chief, and highlighted coverage by The New York Times on a study of guidelines that included a new category for preschool attention-deficit hyperactivity disorder.

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