Something to Dance About: A Gentler Approach to Sickle Cell Transplants

Legacy of firsts

St. Jude has been researching sickle cell disease since before the hospital opened in 1962. One of the institution’s earliest clinicians, Lemuel Diggs, MD, received the institution’s first grant, which was earmarked to study the disorder. A St. Jude patient was also the first in the world to be cured of sickle cell disease with a bone marrow transplant. When the 8-year-old girl underwent a transplant for acute myeloid leukemia in 1983, she was also cured of her sickle cell disease.

Since then, most clinicians have used high-intensity chemotherapy before sickle cell disease transplants, just like transplants done to treat patients with leukemia. By the early 2000s, however, investigators started exploring less-intense regimens, testing chemotherapy doses that were 70 to 90% of standard doses.

About six years ago, sickle cell disease researchers at the National Institutes of Health (NIH) discovered that no up-front chemotherapy-based conditioning was required to cure some individuals with sickle cell disease who received fully matched transplants from their siblings.

“That made transplant much more appealing to patients, but it had a problem: As conditioning intensity decreases, the risk of graft rejection increases,” Sharma says. “So, we increased the conditioning intensity by adding just a little bit of chemotherapy to prevent rejection.”

The SCDHCT clinical trial aims to enroll 40 patients under age 25 who have severe sickle cell disease — 20 individuals with fully matched sibling donors and 20 with half-matched, or haploidentical, donors.

Not every patient has a brother or sister who is a perfect match, so the ability to use a parent (a half-matched donor) is an exciting option. The SCDHCT clinical trial is also appealing to many patients because it offers a gentler treatment regimen than has been used in the past.

“Patients in our study receive reduced-intensity conditioning, than what is used in standard transplants,” Sharma explains. “We hope this approach will successfully cure sickle cell disease with much less short- and long-term toxicity.”

Exceptional care

St. Jude has a long-standing commitment to improving the lives of children with sickle cell disease. The nurse-to-patient ratio of 1:3 for treatments to manage symptoms and 1:1 for patients in the ICU after transplant is unmatched by most other hospitals.

Physician Assistant Darla Pickett oversees chronic blood transfusions for St. Jude patients with sickle cell disease. She provided care to Anaiya for five years leading up to the transplant.

“Medication helped to lower Anaiya’s iron levels but then caused some kidney issues,” Pickett says. “Chronic transfusions were helpful to alleviate her symptoms, but they were never going to be a cure.”

Sonja Carruthers, Anaiya’s grandmother and guardian, heard about SCDHCT during a talk on sickle cell disease at the hospital.

“I signed her up for the study right away,” Carruthers says. “Transplant was her best chance to be cured and to leave behind transfusions and their side effects.”

Careful choreography

Like Anaiya’s dance moves, transplantation involves carefully executed, well-timed steps that begin a couple of months in advance. First, the patient receives a two-drug preconditioning treatment by mouth to reduce the risk of rejecting the donor stem cells, known as a graft.

Next, the individual receives reduced-intensity chemotherapy and low-dose total body radiation. This prepares the patient to receive the donor’s stem cells on transplant day.

After the transplant, the patient receives medications to help prevent graft-versus-host disease and graft rejection.

Anaiya received a haploidentical transplant from her mom in August of 2020. She was the first person in the clinical trial to receive a half-matched transplant, and her treatment team says she has responded well to the treatment.

Nurse practitioner Amanda Kennedy met Anaiya a couple of months before her transplant and will continue to care for her during the next several years. The bond they have developed is strong.

“Anaiya didn’t want to talk with me at first. She’s very picky about who she lets in,” Kennedy says. “But once she does, that girl’s got attitude. She’s a little stubborn and sassy, in all the right ways.

“Anaiya’s a fighter,” Kennedy continues. “She lost her hair, had nausea, pain and other issues, but she bounced back quickly, and now she wants to give back. She spoke with another of one our young patients who was coming for transplant on this protocol. Anaiya gave her a heads up, sharing what she had been through and what to expect.”