Half-Matched Transplants,
Whole Hope for Cures

 

A new study for half-matched transplants aims to cure high-risk blood cancers.

By Jane Langille; Photos by Seth Dixon and Ann-Margaret Hedges

 
Clayton and his mom

The ultimate gift: 
Clayton’s mom, Natalie, donated blood stem cells through a process that collects and separates stem cells from blood taken from a vein in the arm. “Clayton received my cells just 21 days from when they saw warning signs that his leukemia might come back,” she says. “I don’t think things happen that fast anywhere else.”

 
 

EVER SINCE 7-year-old Clayton Pinner was diagnosed with a rare form of B-cell acute lymphoblastic leukemia (ALL) in November 2018, he has wanted to know everything about his cancer and his treatments. At St. Jude, Clayton’s nickname is “BossMan” — a moniker that’s even emblazoned on his T-shirts and shoes.

Clayton’s treatment began when he enrolled in a St. Jude clinical trial that used targeted therapy to attack his leukemia.

 

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“The best available chemotherapy decreased his level of disease, but some cancer remained,” recalls Aimee Talleur, MD, of St. Jude Bone Marrow Transplantation and Cellular Therapy. “Clayton’s B-cell ALL has a genetic factor called hypodiploid, which only affects about 2% of patients, making it harder to treat.”

Clayton received CAR T-cell therapy, an approach that engineers a patient’s own disease-fighting T cells to target and destroy cancer cells. That treatment successfully eliminated his cancer cells, but his normal B cells started to return — a warning sign of potential relapse.

Clayton’s best option for a permanent cure was a blood stem cell transplant. But no family member was a perfect match, and none was found in bone marrow registries.

Fortunately, there was another option. Clayton enrolled in a new trial for patients who lack matched donors. The study, called HAP2HCT, aims to kill any remaining cancer cells, reduce the risk of graft-versus-host disease, and help patients recover a strong immune system as quickly as possible.

Aimee Talleur, MD

Aimee Talleur, MD

The Best Choice

A transplant can be an option for children who have blood cancers that have not responded to other treatments.

Immature blood stem cells found in bone marrow develop into all types of blood cells. An allogeneic transplant replaces damaged stem cells with healthy ones from another person. Proteins called human leukocyte antigen (HLA) markers must match on the donor and recipient cells. If the match is not perfect, the donor’s cells may attack the patient’s cells, a condition called graft-versus-host disease.

Seventy percent of patients lack perfectly matched family members. It can be difficult to find a matched donor in bone marrow registries. In those cases, a haploidentical, or half-matched, transplant may be an option. Biological parents are always half-matches for their children, and biological siblings have a 50% chance of being a half-match for one another.

With one of the largest pediatric bone marrow transplant programs in the world, St. Jude has performed thousands of transplants since 1982. For nearly two decades, St. Jude researchers have been pioneering and refining haploidentical transplants to push survival rates higher.

 
 

A new trial for patients who lack matched donors, HAP2HCT aims to kill remaining cancer cells, reduce the risk of graft-versus-host disease, and help patients recover a strong immune system as quickly as possible.

 
 

Mom as Donor

First, Clayton received chemotherapy to destroy his bone marrow. Natalie Pinner, Clayton’s mom, donated blood stem cells through a process that collects and separates stem cells from blood taken from a vein in the arm.

“Clayton received my cells just 21 days from when they saw warning signs that his leukemia might come back,” Natalie says. “I don’t think things happen that fast anywhere else.”

About two weeks after the infusion, Natalie’s stem cells were creating new blood cells in Clayton’s bone marrow. At that point, he received a second infusion from Natalie of her donor memory cells — mature white blood cells that remember how to prevent people from becoming sick from common infections.

Before the infusions, Natalie’s donor cells were engineered in the lab to remove certain types of T cells: those with cell surface receptors made up of an alpha protein linked to a beta protein, and those that express a molecule called CD45RA.

“We take out the T cells that can make patients sick and leave those that can fight infection and any remaining leukemia cells,” explains Brandon Triplett, MD, chief of the hospital’s Bone Marrow Transplant Clinical Service. “If we remove all of the T cells, recipients experience less graft-versus-host disease, but there are more infections and relapses.”

Brandon Triplett, MD

Brandon Triplett, MD

An earlier trial called HAPNK1 used CD45RA-depleted donor memory cells in haploidentical transplants. Scientists noted promising results among the 70 patients.

“We saw some of the best outcomes ever,” says Triplett, who led the trial. “The relapse rate and the risk of dying from complications were very low, and life-threatening viral infections were well-controlled.”

Patients in HAPNK1 received donor memory cells in one dose. In HAP2HCT, doctors are monitoring patients weekly for 15 weeks and treating them with smaller doses of donor memory cells as required. Clayton also received a drug that attaches to T cells at one end and to leukemia cells at the other. This drug activates the T cells to destroy leukemia cells while stimulating the growth of more T cells.

 
 

Seventy percent of patients lack perfectly matched family members. It can be difficult to find a matched donor in bone marrow registries. In those cases, a haploidentical, or half-matched, transplant may be an option.

 
 

Full Circle

Clayton has faced cancer with a maturity far beyond his years. After understanding the rationale for each treatment, he said, “You’ve gotta do what you’ve gotta do.”

The boy painted the motto on his hospital room’s window to encourage other children undergoing treatments.

Natalie says it’s interesting how things come full circle.

“I volunteered at St. Jude on Saturdays when I was in high school,” she says. “I ran the Happy Cart for the Child Life program, taking toys to children. Now it’s my son who is enjoying toys from the cart.”

When he grows up, “Boss Man” wants to be a cancer researcher and find more ways to fight cancer.

St. Jude has been a blessing to us,” Natalie says. “Everyone is on the same team. We are where we are because other children signed up for clinical trials. It’s rewarding to think that down the road, Clayton’s experience is going to help other children.”

 
 

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