Shelby’s Gene Therapy Journey for Beta Thalassemia

The agency in Guangzhou, China, that arranged three-year-old Shelby’s adoption by a family in the US disclosed to Michelle and Adam Campbell that Shelby had beta thalassemia disorder. Yet, that did not deter the Campbells after they had diligently raised thousands of dollars through various fundraisers to pay for her adoption.

Shelby was two years old when the Campbells brought her home to their small town in southern Pennsylvania. The day after the homecoming, Shelby’s parents took her to Children’s Hospital in Philadelphia to receive a blood transfusion. Due to the nature of the disorder, Shelby will require a transfusion every three weeks, perhaps throughout her lifetime.

As reported in Medriva News, Beta thalassemia is an inherited blood disorder whereby the body does not produce a sufficient amount of beta-globin, a subunit of hemoglobin. This causes a reduction in the iron-containing protein that transports oxygen to the cells.

When Shelby had just celebrated her sixth birthday, her physician, Dr. Tim Olson, told her parents that her medication is no longer working. For a while, the doctors continued to administer blood transfusions, but they had difficulty managing side effects.

It seems that after several years of successfully administering beta thalassemia medication, the meds that rid the body of excess iron from transfusions (chelation meds) were no longer working. Dr. Olson tried the only other alternative to prevent organ damage. It was an older treatment that was pumped through a needle under her skin for twelve hours every day. It did work for a short time but also interfered with her dance classes and field hockey games.

Within a year, emergency measures had to be put in place to avoid damage to her organs. Bluebird Bio’s newly approved Zynteglo, a one-time treatment at a cost of $2.8 million, was recommended.

The transplant replaces Shelby’s deficient cells with stem cells that produce red blood cells accurately. It takes approximately six months for the transplant to take effect. In Shelby’s case, it amounted to almost one year. The goal is to eliminate the need for transfusions.

About the Treatment

Several months after being advised of her doctor’s recommendation, Shelby and her mother were ready to begin the new therapy.

With Dr. Tim Olson’s medical team in attendance, he connected two syringes filled with a light-colored liquid to a tube leading to a port in Shelby’s chest. The syringes contained Shelby’s modified stem cells that were collected several months earlier and were now being reinfused into her body. Both syringes were emptied in eight minutes.

Now the six-month (or more) wait begins.

During the waiting period, a reporter from STAT News followed Shelby and her family for over a year, visiting her in the hospital and speaking with those who treat the disorder for a thorough understanding of how this ‘miracle’ affects patients and their caregivers.

Michelle told STAT that although they are hoping for a miracle, she is not necessarily looking forward to it.

As expected, the initial six-month wait lasted about one year. Shelby was in the hospital for seven weeks receiving toxic chemotherapy that was required to clear out defective cells.

She endured high fevers and mouth sores. As her hair began to fall out, Michelle attempted to cut it very short. Shelby finally opted to have her head shaved but had trouble at first looking at herself in the mirror.

One difficult preventative measure during her immune system’s recovery was Shelby’s isolation from her friends and her school for seven months.

Shelby remained in a germ-free room as a protection against infection and was fed via a feeding tube. Michelle washed her toys each night and performed general nursing duties for her daughter.

The Campbells felt that at some time in the near future, they might try to have Shelby participate in a clinical trial for one of the gene therapies. They wanted to be certain that their daughter had a chance to harvest her eggs before she received chemotherapy, which causes infertility. However, Shelby was adamant that she wanted to adopt children when she was older.

As it turned out, searching for a bone-marrow donor was almost impossible, as the Campbells did not have any information about Shelby’s biological parents. In addition, clinical trial participation was rarely available. Yet as it turned out, the Campbells were in a perfect place for Shelby to receive the new gene therapy. It seemed that several factors had meshed together making it possible for Shelby to receive Zynteglo.

It must be noted that receiving any stem cell transplant is a long process. Patients become their donors, with, of course, help from science.

The first step was to collect Shelby’s stem cells. The cells were circulated in a machine, and the desired cells were separated out. They were then couriered to Houston, Texas, where Lonza, Bluebird’s partner, used another method called a working hemoglobin-producing gene. This whole process may take only a few days, but the subsequent FDA quality testing that is required may take between seventy to ninety days.

It was now time for Shelby to leave the hospital and go back to her home. It took a while for her energy to return as she became fatigued due to her body regenerating platelets, stem cells, and blood cells. Although she wanted to rejoin her gymnastics class, she was unable to find the energy.

Shelby went back to the hospital in Philadelphia for surgery to replace a central line for a semi-permanent port. In addition, her ovarian tissue was harvested to be used in a clinical trial with the intent of preserving fertility. She also had chemotherapy for four days to kill native stem cells and provide room in her bone marrow for the cells that had been corrected.

An additional precaution to which her mother attended was being provided with a new toothbrush every time she used one. This was in the event that bacteria were growing in an old brush. The goal was to prevent mouth sores, but they seemed to occur continuously.

Shelby had a feeding tube implanted the day after surgery. However, she threw up the tube due to her not being able to tolerate the mouthwash and it had to be reinserted. By the time she left the hospital, the tube had been reinserted five more times.

After the infusion, about day nine, unusually heavy mucus began to accumulate. She developed fevers and began to have sores in her gastrointestinal tract.

Dr. Olson explained that these symptoms persist for several weeks until the new cells begin to grow. In fact, after her platelet and blood cell counts hit bottom on the eleventh day, and after a very high fever, she had to receive platelets almost every day. Injections were finally required to jump-start the production of blood cells.

Finally, in August, they returned home. Even though Shelby was isolated at the hospital, nurses and general staff still attended to her. Being at home and tending to Shelby as a nurse and mother was at first overwhelming but eventually, for the next six months, they all settled into a routine.

Michelle mentioned that there is so much to absorb that somehow the side effects that the children experience are not necessarily discussed.

Adam and Michelle were able to get help from their family to care for Shelby while they were at work. Michelle cautions other families to be certain they have that support before committing to the procedure.

Although Shelby will not be declared free of transfusions for one year, her counts are slowly increasing. For the first time in her life, her body is making its own hemoglobin. She has not needed a transfusion for the past four months since her last hospital stay. Shelby actually removed her own feeding tube, and the medical team is comfortable seeing her less frequently.

In a year or two, Shelby will settle in to having a normal life thanks to Zynteglo.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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