CINCINNATI -- Sophia Kappen was a beautiful little girl, her mother remembers. She was smart and spirited, willing to try anything.
"She kept her two brothers in line, always," Amy Kappen said. "She was kind of the boss of the house -- wise beyond her years."
When she was 5 years old, Sophia wasn't feeling well for a few weeks. Her condition kept going back and forth. Her family was blindsided to hear she had leukemia.
"Doctors told us, 'Don't be worried. If you're going to get pediatric cancer, this is the best kind to get,'" Amy Kappen said. Sophia's family was assured cure rates were greater than 90 percent, and that treatments had come a long way.
Sophia was among the 10 percent who aren't cured. A year to the date after her diagnosis, she was gone. Before she died, Sophia was part of a clinical trial that will help other children. According to a doctor at Cincinnati Children's Hospital Medical Center, it "changes the ball game."
Sophia started out with a more traditional treatment: chemotherapy. About a month into it, Amy Kappen said her daughter suffered a serious seizure as a side effect.
"It was at that point it brought us to our knees," she said. "We were like, 'This is scary. This treatment is really harsh on these little bodies.'"
Sophia made it through and went into remission for three months. Then, her mother said, doctors thought she had another side effect from chemotherapy. Instead, the cancer returned faster than the doctors had seen before.
"We know that when children relapse that early, their survival rates go down significantly," Amy Kappen said.
Sophia's primary oncologist at Children's knew about a clinical trial involving chimeric antigen receptor, or CAR, T-cell therapy. It started about three years ago at the University of Pennsylvania.
Dr. Christine Phillips treats leukemia and lymphoma patients at Children's Hospital. She said CAR T-cell therapy is different than most drugs because it's actually alive. A child's T-cells -- the white blood cells that fight infections -- are extracted from the body. They're re-engineered and trained to fight cancer cells. Then, they're put back into the child's body.
"That creates an inflammatory response the ultimately kills the leukemia cells," said Dr. Javier El-Bietar , a bone marrow transplant physician at Children's.
In a global trial involving 68 children, 83 percent went into remission. Their disease wasn't detectable.
"These are kids who had stopped responding to chemotherapy, kids who had relapsed," Phillips said. "They had been treated with a lot of other therapies and were not responding.
"There really is an impressive number of children who can get into remission with this therapy."
Shortly after Sophia's cancer returned, her doctors discovered she was resistant to chemotherapy. Her family knew time was working against them, and they had just a few options. They decided to pursue CAR T-cell therapy.
"She looked pitiful," Amy Kappen said. "The cancer was just sucking the life out of her. We couldn't help but say, 'This isn't the way she's supposed to go out.'"
Sophia and her family went to Philadelphia for the treatment. She received CAR T-cell therapy in November 2016. Then came the "storm."
"When those T-cells expand in your body, you get the worst flu of your life," Phillips said.
Patients can get high fevers, chills and low blood pressure and have respiratory problems. The side effects are temporary, but about one-third of patients, including Sophia, end up in the intensive care unit to help manage them.
Once the storm passed, Sophia's family saw her coming back to them. "She started to have a zest for life again, and she was really fighting," Amy Kappen said. "The transformation from October to December of last year was unbelievable."
Doctors do a check 28 days after the T-cell infusion; Amy Kappen said her daughter's cancer went from greater than 90 percent through her bone marrow to less than 1 percent.
Because she was in a clinical trial, though, Sophia didn't get the treatment right away. She had a three-and-a-half month wait, and her cancer mutated, became more aggressive. In Philadelphia, her family learned she had tumors throughout her body. The tumors shrunk with treatment, but they never went away. Three months later, in January, doctors found Sophia's cancer was back and too aggressive to stop.
She died in her parents' arms April 5 . She was 6 years old.
The CAR T-cell therapy gave Sophia, and her family, a few more months.
"Even though she couldn't walk, she had come back to us," Amy Kappen said. "We felt like our daughter had returned so we got to see her before we had to say 'goodbye.'"
The clinical trial continues, and the U.S. Food and Drug Administration recently approved the treatment under the commercial name Kymriah. It costs about $450,000, but Phillips said most insurance providers cover it. Instead of waiting three months like Sophia, the T-cells are ready in about three weeks.
The treatment isn't available everywhere because hospitals have to be trained for the severe side effects, like Sophia had.
And although doctors caution it's too early to tell, Phillips hopes CAR T-cell therapy might replace some of the toxic chemotherapies used in cancer treatment now.
"This changes the ball game," El-Bietar said. "This offers families in those circumstances who either have relapsed, have highly aggressive leukemia or leukemia that's just persistent another therapeutic option."