Regenerative Medicine and Stem Cells Technologies

Emily Whitehead is the first pediatric patient in the world to receive CAR T-cell therapy for relapsed/refractory acute lymphoblastic leukemia (ALL). She is a singular figure in the annals of medicine.

It has been 10 years since the only child of Thomas and Kari Whitehead of Philipsburg, PA, received an infusion of CAR T cells at the hands of a collaborative medical team from the Children's Hospital of Philadelphia (CHOP) and the Hospital of the University of Pennsylvania.

Tremendous progress has flowed—gushed—from the effort to save Emily Whitehead; many more lives have been saved around the globe since that fateful—yet nearly fatal—undertaking.

In 2010, Emily, then 5 years old, went from a being a healthy youngster one day, to a child diagnosed with ALL. After 2 years of intermittent chemotherapy, she continued to relapse. And when a bone marrow transplant seemed the only hope left, her disease was out of control and the treatment just wasn't possible. The Whiteheads were told by her medical team in Hershey, PA, nothing more could be done.

 It was just the day before that CHOP received approval to treat their first pediatric relapsed/refractory ALL patient with CAR T cells in a trial.

At that time, only a scant few terminal adult patients had ever received the treatment, which is now FDA-approved as tisagenlecleucel and developed in cooperation with CHOP and the University of Pennsylvania. When three adults were treated, two experienced quick and complete remission of their cancers.

On March 1, 2012, Emily was transferred to CHOP and a few days later an apheresis catheter was placed in her neck; her T cells were extracted and sent to a lab. Emily received more chemotherapy, which knocked out her existing immune system, and she was kept in isolation for 6 weeks. Waiting.

Finally, over 3 days in April, Emily's re-engineered T cells, weaponized with chimeric antigen receptors, were infused back into her weakening body. she sunk into the feverish fire of cytokine release syndrome (CRS), and experienced a worse-than-anticipated reaction.

“I can still see Emily's blood pressure dropping down to 53/29, her fever going up to 105°F, her body swelling beyond recognition, her struggle to breathe,” said Tom, of the most nightmarish period of his life. Doctors induced a coma, and Emily was put on a ventilator. For 14 days, her death seemed imminent. “Doctors told us Emily had a one in a thousand chance of surviving,” said Tom. “They said she could die at any moment.” But she didn't.

Medical team members knew if CRS could be overcome, the CAR T cells might work a miracle as they had done for those earlier adult patients. But the CRS was severe.

It was not until the CHOP/Penn team received results from a test profiling cytokines in Emily's body that a new flicker of hope sparked. Though Emily had many cytokine abnormalities, the one most strikingly abnormal, interleukin-6 (IL-6), caught the team's attention. It is not made by T cells, and should not have been part of the critical mix. Though there were very few cytokines that had drugs to target them individually, IL-6 was one that did. So the doctors decided to repurpose tocilizumab, an arthritis drug, as a last-ditch effort at saving their young patient.

But she turned around—unbelievably rapidly. Today, tocilizumab is the standard of care for CRS, and the only drug approved by the FDA for that complication.

“Since we treated Emily, we have treated more than 420 patients with CAR T cells at CHOP. She launched a whole group to be treated with this therapy; thousands have been treated around the world,” Grupp noted. “And, if not for Emily, we wouldn't be in the position we are in today—with five FDA-approved [CAR T-cell] products: four for adults and one for kids. And I think it also important to point out that the very first CAR-T approval, thanks to Emily, was in pediatric ALL.”

“Today, hundreds of pharmaceutical and biotech companies are developing innovations. Hundreds of labs are making next-generation approaches to improve in this area,” June noted. “Today, I'm a kid in a candy shop because all kinds of things are happening. We have funding thanks to the amazing momentum from Emily. She literally changed the landscape of modern cancer therapy.”

https://journals.lww.com/oncology-times/Fulltext/2022/03200/The_Incredible_Story_of_Emily_Whitehead___CAR.1.aspx