Rare. Baffling. Incurable. These are the words a parent of a sick child dreads.
A child such as Ayla, who began to experience severe breathing problems when she was just shy of 2 months old. Tests revealed a seldom-seen defect in her lymphatic system that caused fluid to leak into her chest cavity and build up to dangerous levels. Doctors could drain the fluid, then drain it again and again, but eventually she would lose too much, which would compromise her immune system. Unless they could find a new type of intervention, Ayla would soon die.
Or a child such as Tori. By the time she was 9, her acute lymphoblastic leukemia (ALL) was so aggressive, it had come back twice despite potent chemotherapy. As recently as four years ago, doctors had almost no options for curing such relapsed patients.
But rare and incurable are also words that drive researchers at The Children’s Hospital of Philadelphia. At the core of CHOP’s mission is support for innovative research that translates to new treatments for children with complex conditions. Recently, the Hospital chose two programs that embody that connection between astonishing research breakthroughs and extraordinary clinical care to be its inaugural Frontier Programs. Those two programs — the Lymphatic Imaging and Interventions Frontier Program and the Cancer Immunotherapy Frontier Program — will receive initial funding from the Hospital and programmatic guidance from a multidisciplinary steering committee over the next several years. Eight more Frontier Programs will be designated in the next four years, demonstrating CHOP’s deep commitment to helping even more children thrive, regardless of dire diagnoses.
“The Frontier Programs are cultivating teams that deliver care uniquely available here,” says Joseph St. Geme III, MD, CHOP’s physician-in-chief, chair of the Department of Pediatrics and the executive sponsor of the Frontier Programs. “Then we’ll spread our expertise so that children everywhere can benefit from what we’ve discovered. By the time that happens, the Frontier Programs will already be tackling the next challenge or implementing the next advances in care.”
“The Frontier Programs are a novel way to bring research more quickly to the bedside,” says President and CEO Madeline Bell. “We’re building the clinical programs of the future.”
Leading a revolution
In January, President Obama announced a “moon shot” to cure cancer, but CHOP oncologist Stephan Grupp, MD, PhD, had already set out on that ambitious journey years ago. Childhood cancer survival rates have increased dramatically in the last 20 years, but a small percentage of cases remain treatment-resistant, leaving doctors with frustratingly few options. Grupp vowed to change that, partnering with colleagues in the CHOP Division of Oncology and others to develop the Cancer Immunotherapy Program.
Immunotherapy refers to treatments that harness a patient’s own immune system to help fight disease. For children with ALL, the most common childhood cancer, the personalized immunotherapy involves taking cells called T cells from a patient’s own blood, then genetically modifying them so that they’ll recognize and attack cancerous cells. Doctors at CHOP were the first to begin offering this treatment option in pediatrics as part of a pilot study in 2012. Grupp is serving as lead investigator for a subsequent global trial led by the pharmaceutical company Novartis.
Tori was one of 25 children and five adults who traveled to CHOP to take part in the trial. Initial results, published in 2014, were staggering: Of these patients with previously little hope, 90 percent were in complete remission after one month and 67 percent remained in complete remission after six months.
When Grupp talks of the immunotherapy program, one theme comes across emphatically: He wants to do more. And the Frontier Program funding will help him and his team get started.
He is determined to create additional cell therapies for multiple types of cancer. “Another major goal,” he explains, “is to expand access to and delivery of cell therapy at CHOP so we can accept many more patients than we do now.”
And he’s eager to move beyond the clinical trial phase: “One of our goals right now is to get cell therapy for childhood leukemia FDA-approved within the next 18 months. With Frontier Program support, we think we can make this happen and have the first engineered cell therapy ever approved available to kids across the U.S. and, later, across the globe.”
Marta, a teenager from Norway, couldn’t lie down to sleep. “I felt like I was drowning in my own body,” she says. Like the infant Ayla, her lymphatic system was leaking large amounts of fluid into her chest and abdomen. The lymphatic system, an extensive but rather mysterious part of the body, consists of lymphatic organs and a network of vessels that carry a clear fluid called lymph. Circulation of the fluid helps keep the immune system strong.
Marta’s doctors in Norway had no idea how to locate the leaks. But the two leaders of CHOP’s Jill and Mark Fishman Center for Lymphatic Disorders knew what to do. Yoav Dori, MD, PhD, a CHOP pediatric cardiologist, and Maxim Itkin, MD, have developed a new imaging technique that allows them to see the entire anatomy of the lymphatic system, something that previously hadn’t been possible. Through this imaging, doctors pinpointed the location of Marta’s lymphatic system leaks and sealed them. They did the same for tiny Ayla, too.
Even more remarkable, doctors have only begun to scratch the surface of the ways their research can be applied. Because lymph is nearly everywhere in the body, they keep finding new and exciting avenues to investigate, like detectives pursuing a hot case.
“There were a lot of assumptions about the lymphatic system and how it works with the immune system that weren’t tested,” says Itkin. “We’ve found out that the process is completely different than what was in the textbooks. This has enormous implications — for example, in understanding how HIV infection happens.”
“What we discovered,” says Dori, “could help us understand how cancer cells travel in and out of the lymphatic ducts. It’s huge.”
With Frontier Program funding, Dori and Itkin are able to explore the lymphatic system’s connections, not only with infectious diseases and cancer, but also with conditions as varied as neonatal lung disease and heart failure. The latter, which affects millions of Americans each year, eventually has an impact on the lymphatic system, causing additional complications.
“We can now access a component of the body that hadn’t been accessible,” says Dori.
In the quest to conquer what’s rare and incurable, that’s what a new frontier looks like.