On a recent November morning in Palo Alto, California, a hallway at Lucile Packard Children’s Hospital Stanford transformed into a racetrack.
“Hey, watch this!” announced 6-year-old patient Kruz Davenport, walking out of his exam room and up to the makeshift starting line: a row of blue hospital gloves that Karen Kristovich, his nurse practitioner, had laid out on the hallway’s striped carpet. “Don’t be shy,” said Kruz, encouraging Paizlee, his 4-year-old sister and a fellow patient, to join him. The siblings prepared by removing their hoodies (Kruz’s featured dinosaur spikes, while Paizlee’s had a unicorn horn) and taking their places side by side. The finish line, about 15 feet ahead of them, was Kristovich’s open arms. She counted down from three before letting out an exuberant “Go!”
Kruz and Paizlee reached the finish line to the cheers of Kristovich; their mother, Jessica Davenport; their stem cell doctor, Dr. Alice Bertaina; and their social worker, Liana Zannis. This milestone, a running embrace at the end of a positive hospital checkup, was more than three years in the making. And it would have been impossible only a few short months ago.
The Davenports’ journey to Stanford began 2,200 miles away in the small city of Muscle Shoals, Alabama. In 2016, Jessica and her husband, Kyle Davenport, grew concerned about their then 2-year-old son Kruz’s sensitivity to light. They brought him to a series of specialists to treat what they believed was a vision problem. After many doctor appointments and needle pricks but no answers, Kruz underwent genetic testing. The Davenports were given the crushing news that their son had a rare genetic condition called Schimke immuno-osseous dysplasia, or SIOD, a form of dwarfism that causes immune deficiency, renal failure, and hip dysplasia, among other complications. The average life expectancy for people with SIOD is nine years.
Paizlee, then one-and-a-half years old, exhibited no visible symptoms of SIOD. But Jessica and Kyle knew they were both carriers of the SMARCAL1 gene mutation that is responsible for the condition, so they tested their daughter as a precaution. She received the same diagnosis as her older brother, making them the first pair of siblings in the U.S. to be diagnosed with SIOD—a one in 80 million chance, according to their mother.
Caretaker Voices
Dr. Hanley
Caretaker Voices
Jessica Davenport, mother of Kruz and Paizlee, on finding a treatment team for her kids
Reeling from this news, the Davenports searched for doctors studying SIOD. They hoped to find an emerging treatment but soon discovered that no such research was being done. “There was no treatment plan for SIOD,” recalls Jessica. “It was: Treat the symptoms as they come and try to keep them alive.” Nearly all children with SIOD have T-cell deficiency, resulting in weakened immune systems that put them at higher risk for infection and some cancers. They also suffer from renal failure, which requires dialysis and an eventual kidney transplant. In short, the outlook for Kruz and Paizlee was grim.
The Davenports did, however, find a doctor who previously had led research focused on SIOD and the SMARCAL1 gene mutation. Though his research on the disease was no longer active, he referred the family to his former collaborator, Dr. David Lewis, who spearheads an immunology lab at Stanford Children’s Health and has spent more than two decades researching pediatric immunological conditions.
After hearing the Davenports’ story, Dr. Lewis reviewed the existing research on SIOD and saw the potential in stem cell transplantation as a therapy. He contacted Stanford’s stem cell transplantation team, which suggested that haploidentical stem cell transplantation could address Kruz and Paizlee’s immunological issues. This approach enlists a donor, who is only a half match for a genetic marker found in the patient’s cells, to provide stem cells through a bone marrow transplant. This transplant gives the recipient a new immune system—that of the donor—before the organ transplant they need (in the case of SIOD, the kidney), which increases the odds that the recipient’s body will accept the new organ.
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Dr. David Lewis, director of the Jeffrey Modell Primary Immunodeficiency Center, on how the Davenports’ treatment will impact others
But there were reasons why this course of treatment had long been considered unworkable. Of the five published SIOD patients who previously underwent stem cell transplantation, only one was a long-term survivor. The doctors at Stanford, however, thought that recent advancements in haploidentical transplantation might change the calculus. So they invited that lone surviving patient, who received his stem cell transplant two decades ago, at age 7, to visit the hospital. After gathering all the insights they could from his medical history and evaluating his immune function, a multidisciplinary team of caregivers determined how to best treat Kruz and Paizlee’s symptoms and, hopefully, find a cure for SIOD.
Jessica and Kyle Davenport, in addition to caring for their increasingly sick children (Kruz went into renal failure and began dialysis in May 2017), focused their energies on funding this SIOD research. “We looked at it as our calling to take this on,” says Jessica, “and that’s exactly what we did.” The Davenports’ nonprofit, Kruzn for a Kure Foundation, has raised more than $1.5 million to date, largely through $5 and $30 donations. Besides supporting other research projects, the organization sends Dr. Lewis’s immunology lab $30,000 a month to support its eventual goal of developing a drug therapy for SIOD. Since taking on this project in 2017, Dr. Lewis and the care providers at Stanford have made significant strides.
Drug therapies, however, often take years to develop, and Kruz and Paizlee’s medical needs were pressing. So Stanford’s stem cell transplantation doctors, led by Dr. Alice Bertaina, meanwhile worked to develop a treatment plan involving haploidentical stem cell transplantation to help Kruz and Paizlee before it was too late.
Dr. Alice Bertaina, the medical director of Inpatient Services for the Stem Cell Transplant Program, joined Stanford Children’s Health in October 2017 as part of Stanford’s push to build the Center for Definitive and Curative Medicine. The center is designed to bridge the gap between lab discoveries and cures, especially for stem cell transplants and gene therapy. Upon her arrival, Dr. Bertaina immediately dove into the Davenports’ case when Dr. Lewis asked for her opinion. At 7 a.m. on her second day at Stanford, she was already on the phone with the Davenports’ Alabama care team, working on a game plan.
Dr. Bertaina had a clear proposal in mind: She wanted to use Jessica, Kruz’s mother, first as a stem cell donor and then as a kidney donor. To make this approach successful, Dr. Bertaina manipulates the composition of Jessica’s stem cells in the laboratory. The aim of this procedure is to decrease the risk of infection and eliminate the need for recipients to take antirejection, immunosuppressive drugs for the rest of their lives. It also serves to make stem cell transplants a safer option for patients like Kruz and Paizlee, who don’t have perfectly matched donors.
Caretaker Voices
Dr. Waldo Concepcion, chief of Clinical Transplantation, on what sets Stanford Children’s Health apart
The Davenports’ care team were united by a “research spirit” that Dr. Bertaina says is core to Stanford Children’s Health’s approach to care. “There’s a straight connection between laboratory and clinical care here. For example, through our Center for Definitive and Curative Medicine, we can accelerate cell and gene therapy from the lab into clinical trials into cures for children,” she says. “We combine that expertise with a respect for the human dimension of the family. I think that’s the magic recipe for really making this kind of work successful and gives this hospital its unique role.”
Dr. Waldo Concepcion, Stanford’s chief of Clinical Transplantation and the lead surgeon on Kruz and Paizlee’s care team, also points to the care providers’ willingness to take on difficult cases like the Davenports’ as a uniting quality across the institution. “It takes courage to look at problems as not just more of the same,” says Dr. Concepcion. “It’s that effort to go and say, Well, how can we do this together and get institutional support? And most importantly after that, share it with the world.”
By January 2019, the Davenports’ multidisciplinary team felt secure in the groundbreaking treatment method it had devised. So Jessica and Kyle sold their home, packed what they could into a car, and moved across the country. Once the family arrived in Palo Alto, the kids’ treatment plan was set in motion: Kruz received a stem cell transplant from Jessica in February 2019. Just shy of half a year later, in July, having fully received Jessica’s immune system, Kruz received one of his mother’s kidneys. After watching her son grow weak during renal failure, which made him unable to walk for 11 months, it was a joy to see him not only back on his feet—but walking and even running. “He literally has a brand-new life,” says Jessica.
Dr. Concepcion proudly calls Kruz “a pioneer.” He’s the first pediatric patient to intentionally receive this type of haploidentical stem cell treatment followed by a solid organ transplant from the same donor—and it was a success. The tolerance that Kruz has achieved has required no immunosuppression and has been previously “unheard of in the world of pediatric kidney transplantation,” says Dr. Concepcion. Now Kruz can begin the normal life—full of playdates and school—that he never had, with hip replacement surgery to follow early next year.
Caretaker Voices
Dr. Alice Bertaina, medical director of Inpatient Services, Stem Cell Transplant Unit, on Kruz and Paizlee
Paizlee is already following in her big brother’s footsteps. Her father, Kyle, donated his blood stem cells to her in August 2019. She’s currently on dialysis but is expected to be ready for a kidney transplant from her dad in February 2020.
It’s worth noting that this cutting-edge treatment plan won’t only benefit the Davenport kids. “My children were the ultimate test run,” says Jessica. “I remember Dr. Alice telling me, ‘How we treat Kruz and Paizlee is how we’re about to start treating the rest of the world.’” The research that’s taking place in Dr. Lewis’s laboratory, for instance, will also likely lead to greater knowledge of the organ systems that are affected by the SMARCAL1 gene mutation, including the kidneys and blood vessels. Dr. Bertaina believes that her approach could also be used for liver, intestine, or even lung transplants. “We can really expand this approach to hundreds of disorders and children that require solid organ transplantation but right now don’t have a specific treatment available,” says Dr. Bertaina. This is why the Kruzn for a Kure Foundation now also is supporting a postdoc research effort in Dr. Bertaina’s laboratory to optimize haploidentical stem cell transplant for SIOD and other patients.
Meanwhile, Kruz and Paizlee’s futures, once thought to be painfully short, now stretch out before them. The same day that they raced down the hospital hallway, they also prepared to return home to Alabama, with a plan to come back to Stanford Children’s Health for Paizlee’s kidney transplant. To celebrate this long-awaited occasion, the hospital staff threw the Davenports a “see you soon” party. Jessica was full of gratitude, excitement, and nervousness at leaving behind their care team, which she describes as family. There was comfort, though, in considering how far Kruz and Paizlee had come—and the many kids who might be impacted by the success of their treatment.
“Before this opportunity was available, their diagnosis just felt like a dark hole. You didn’t really see the way out,” says Jessica. “Now that this is successful, in that dark hole you finally see the light.”
Read more stories like this at stanfordchildrens.org
