New Drug Regimen Proves Ideal for Patient with Rare Genetic Disease

In golf, the best shot isn’t always the one that goes the furthest. Sometimes, a golfer should “lay up,” or play conservatively. Exchanging power for precision and avoiding potential hazards can set them up for what’s next.

Avid golfer Evan Cornelius, 20, understands this better than most. So when it came time for him to decide whether or not he would partake in an ongoing clinical trial at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, he approached it as only a golfer could: by weighing the long-term gains and taking the shot.

A rare and tricky disease

Cornelius was born with a rare disease called dyskeratosis congenita (DC), a genetic disorder that affects the entire body, including the bone marrow’s ability to make blood cells. People with DC aren’t able to maintain the ends of their chromosomes, resulting in short telomeres.

Telomeres are long repeats at the end of the DNA that act as a “clock” for cells, naturally getting shorter each time the cell divides. Once these telomeres reach a certain length, they will trigger the cell to stop dividing and instead die off. In the case of patients with DC, their cells cannot properly replenish themselves because the number of times these cells can divide has been drastically reduced. This often leads to bone marrow failure, organ failure, and even certain types of cancers.

Cornelius was exhibiting symptoms of DC since birth, but he wasn’t officially diagnosed with the disease until he was four years old. At age 10, he was put on androgen therapy — a steroid regimen that is known to temporarily improve blood counts in roughly 60% of individuals with this disease.

While the androgen therapy was effective for Cornelius, it was never designed to be a permanent fix. He would ultimately need to undergo a stem cell transplant.

A new kind of transplant regimen

Due to his condition, Cornelius was at a higher risk for serious, life-threatening complications.

During a stem cell transplant, patients typically receive chemotherapy and/or radiation prior to receiving their donor stem cells. This combination suppresses the immune system, eliminates any cancer cells, and creates space for the new stem cells.

However, there is collateral damage to other parts of the body. In patients with DC, the standard transplant regimen carries higher risk, because it isn’t clear how they will handle the chemotherapy and radiation. This leaves them highly vulnerable if they cannot tolerate it.

In 2012, Suneet Agarwal, MD, PhD, co-program leader of the Stem Cell Transplant Center at Dana-Farber/Boston Children’s, introduced a new protocol to help patients like Cornelius. The idea was to offer a radiation- and alkylator-free bone marrow transplant regimen prior to the transplant. This new therapy would eliminate all radiation treatment as well as the alkylating or DNA damaging agents of chemotherapy, leaving the less toxic chemotherapeutic fludarabine and the antibody alemtuzumab to work as immune suppressants.

The ultimate goal was that this new protocol would still be strong enough to attack and overpower the blood and immune system, but gentle enough to spare the rest of the body. 

“Radiation and alkylating agents were previously viewed as necessary; no one thought you could remove them and still have a successful stem cell transplant,” adds Agarwal. “For patients and their families, we often explain this new protocol as a way to more gently ‘till the soil’ (making them suitable for transplant) without ravaging the garden to the point that nothing can grow.” 

Lining up the shot  

Cornelius and his North Carolina family first came to Dana-Farber/Boston Children’s for a consultation in 2014, and three years later, elected to undergo the transplant. During those three years, a lot changed: The less toxic protocol was being used nationally for patients with DC, Cornelius’s androgen therapy was starting to become ineffective, and he had just recently graduated high school (allowing him to complete the procedure before starting college).

With all of this in mind, Cornelius saw the benefit of forgoing the standard treatment for this more precise one.

“I was ready,” says Cornelius. “I thought, ‘This is something I have to do and accomplish to make myself better.’”

Even with the reduced therapy, Cornelius was still sensitive to the medication. But as the days turned into weeks, Cornelius slowly engrafted (meaning the new stem cells were accepted by his body) and began to improve. Cornelius underwent the procedure in August, and by December, he was allowed to return to North Carolina.

“This regimen was extremely important for him and his success,” says Agarwal.

Planning ahead

While the transplant was a success in correcting the blood’s ability to regenerate, it cannot cure Cornelius’s disease altogether. Doctors still need to monitor him and intervene if and when a new problem arises. However, because of the transplant, Cornelius will be able to receive a future transplant (such as a liver transplant) if needed.

“If the stem cell transplant is successful, it can get you over one of the most life-threatening humps,” Agarwal notes.

Since the procedure, Cornelius had complications that resulted in the replacement of both of his hips as well as his shoulders. His last surgery took place in June 2019, and since then, Cornelius says he feels “pretty good.” In fall 2019, he enrolled at Campbell University — and he’s even been able to return to the golf course.

“It was great to get back out there, have fun, and hit the ball again,” he recalls. “Just walking the course felt really good and I was glad to be outside and actually doing something.”

“Evan has been through a ton and is some kind of superhero who has just powered through all of it,” adds Agarwal.

Treating the whole body

As of now, researchers are still working to develop a medication that can lengthen an individual’s telomeres. By doing so, doctors will be able to treat the patient head to toe with a single procedure, rather than having to deal with one issue at a time.  

While Cornelius is hopeful there will one day be a medication for DC, it’s not top of mind for him. Instead, he’s focused on living in the moment and enjoying each day.

“I try not to think about what might go wrong and instead deal with it when it happens,” Cornelius says. “If you’re worrying all the time, you’ll never do anything. You just have to go out there and live your life.”