Gene Therapy Cures Soccer-Loving Boy of Beta Thalassemia

Karar left his monthly transfusions behind after gene therapy

When the Iraqi national soccer team takes the field during this summer’s FIFA World Cup, they’ll have a superfan cheering them on while visiting his family in Iraq for the first time in years.

Some might say it’s a bit of a miracle that the Iraqi team made the World Cup after a 40-year drought and being the last team to qualify.

The fact that 8-year-old Karar can visit Iraq this summer is a miracle too, of the medical variety.

Karar loves school, reading, Super Mario, and, of course, soccer.

“Whenever I saw him, he was always wearing a soccer shirt or a Super Mario shirt,” said Tami John, MD, the director of Clinical Gene Therapies at the Bass Center for Childhood Cancer and Blood Diseases and one of Karar’s doctors. “I remember one time he drew this really detailed picture for our clinic with all the flags of his favorite soccer teams around the world. He’s such a bright young boy.”

Karar has beta thalassemia, a blood disorder that affects the body’s ability to make enough hemoglobin.

Hemoglobin is a protein in red blood cells that carries oxygen from the lungs to the rest of the body. Hemoglobin is made up of two alpha-globin chains and two beta-globin chains. Due to genetic mutations passed down to Karar, his body cannot make beta-globin chains well, which affects his ability to make red blood cells.

Since Karar couldn’t make red blood cells effectively on his own, he needed blood transfusions every three to four weeks, starting in the first year of his life, to keep his hemoglobin in a safe range to help him grow. Before the next transfusion, Karar would become increasingly fatigued.

Each transfusion took most of the day, which meant lots of time away from school. And the frequent transfusions also increased the amount of iron in Karar’s blood. Because patients with thalassemia don’t use iron to make red blood cells, they already have higher-than-normal amounts of iron in their body, and repeated transfusions further increase iron levels. Extra iron can build up in the liver, heart, and other organs, causing long-term health problems. Karar was on several medications to help reduce the amount of iron in his body, and he also had to have frequent blood draws and MRIs to monitor his iron levels.

Karar and his family were interested in a curative treatment so he could stop the transfusions. When they first started receiving treatment at the Bass Center, the only curative treatment option was a stem cell transplant. Karar didn’t have a fully matched stem cell donor, so his stem cell doctor, Ami Shah, MD, was planning for a haploidentical, or half-matched, transplant. But in patients with thalassemia, doing a transplant with a half-matched donor increases the risk of graft-versus-host disease, where the donor immune cells attack the recipient’s body, or of the donor cells ultimately being rejected by the recipient’s body.

Then, a gene therapy for patients with beta thalassemia who need regular transfusions, Zynteglo, was approved by the U.S. Food and Drug Administration. Stanford was one of a few centers that participated in early research trials for gene therapy for beta thalassemia.

“There’s no graft-versus-host disease risk with gene therapy, and for this gene therapy in particular, we have data showing that 90% of patients don’t need blood transfusions after therapy, and the other 10% need them far less frequently,” said Dr. John. “The bar is fairly high with gene therapy.”

Once the pieces were in place and Karar could start the gene therapy process, he and his family were excited for the life-altering change to come.

“They are the most grateful family,” said Dr. John. “Karar’s mom cried when I said we’re finally moving forward with gene therapy. They were so patient throughout the process.”

The gene therapy Karar received is an ex vivo gene therapy, where cells are modified outside of the body. The process started by removing some of Karar’s blood-forming stem cells (cells that can go on to become red blood cells and other blood cells) through a process called apheresis. The gene therapy Karar received uses a viral vector—parts of a virus that can’t get you sick but can bring the new gene into your cells—to add a working copy of the mutated gene to his stem cells.

Next, Karar was given chemotherapy to kill the existing cells inside his bone marrow and make room for the gene-modified cells. He fought through hair loss, nausea, and mouth sores.

Then, the modified stem cells were infused back into Karar, where they found their way into his bone marrow and started to grow and make normal blood cells.

Karar was in the hospital for about 50 days, including preparing his body for gene therapy and recovering after the procedure. The modified cells slowly took hold in Karar’s body, and as they did, he no longer needed blood transfusions. Three months after receiving the gene therapy, Karar was back at school.

He’s now almost two years out from his gene therapy. These days, instead of having to visit the hospital for monthly blood transfusions, Karar comes for the opposite procedure—bloodletting, where small amounts of blood are removed from his body to help reduce the amount of iron in his blood.

“It’s often emotional for families and care teams; the family has spent years coming in to have blood put into their child’s body and now we’re taking it out and throwing it away,” said Dr. John.

Because the gene therapy has transformed his cells’ ability to use iron to make red blood cells, and because he no longer needs transfusions, his iron levels are expected to return to normal in another year or two. Then Karar will need to visit the hospital even less.

Already, being able to visit every three months for bloodletting instead of every month for a transfusion has enabled Karar and his family to visit family in Iraq this summer.

“Before, we couldn’t travel to Iraq because we could only go for a month and we didn’t want to be too far from the hospital,” said Karar’s father, Haider. “But now we can travel for three months. Since Karar was young, we had been waiting for a matched stem cell donor to come along, but things are so much better now, thanks to God and thanks to Karar’s doctors and nurses.”

Karar’s care team is also thankful for his family’s support throughout Karar’s medical journey.

“Karar is so full of life, and since gene therapy, I have seen him grow substantially,” said Kelly Riot, MSN, CPNP, a nurse practitioner on the hematology team who cared for Karar for years before the gene therapy. “Karar’s parents have been a tremendous source of support for Karar. They have always had a positive outlook and have trusted his medical providers to do everything we can to take the best care of Karar. They are truly wonderful human beings, and I feel grateful to have the opportunity to be a part of Karar’s care team.”

With his thalassemia behind him, Dr. John is excited to see what Karar will accomplish in the future.

“He’s still so young, so hopefully he doesn’t have to worry about his thalassemia hindering or limiting him in any way,” said Dr. John. “Especially for someone who has family ties in another country, now he can take vacations, and he doesn’t have to miss as much school to visit the doctor. Now he’s even more energetic—maybe he’ll be a soccer star one day.”