Saro Armenian, D.O., M.P.H., director of City of Hope® Children’s Cancer Center and the Barron Hilton Chair in Pediatrics, says he ponders one question every time a young person with leukemia sees him for the first time.
“For me, when a new patient walks in and we start talking about treatments [such as stem cell transplants], in the back of my mind I’m thinking beyond treatment,” he said. “It’s imperative that we ask, ‘How do we optimize the [additional] years we are gifting the patient?’”
It is not a simple question. Yes, stem cell transplants save lives, and when those lives belong to adolescents or young adults, the “gift” is truly remarkable, providing possibly many decades of life.
But what kind of life?
Muscle Loss in Stem Cell Transplant Patients
The stem cell transplant process, from the preparatory work to the procedure itself to recovery, is challenging and can last several months. During that time, a variety of forces can ravage a young patient’s body, depleting and destroying significant amounts of muscle at precisely the time when muscle should be growing and developing.
“In most of us,” explained Rusha Bhandari, M.D., M.S., assistant professor in the Department of Pediatrics and medical director of the Childhood and AYA Cancer Survivorship Clinic, “we build muscle mass until about age 30 or 40, and then there’s a steady decline.” But these young patients experience a faster than normal muscle depletion. Consequently, “some of these folks, by the time they reach their 30s, can look 30 years older.”
The culprits in this muscle theft are many. Spending week after week in a hospital bed causes atrophy. Nutrition suffers: the chemotherapy and/or radiation necessary for the transplant leads to nausea, fatigue, vomiting, mouth sores and loss of appetite. Inflammation, an enemy of muscle health, can be seen with graft-versus-host disease. The steroids administered to treat inflammation can also negatively affect muscles.
Muscle loss is more serious than many people realize. Muscle plays a pivotal role in regulating vital systems. “Our muscles are responsible for how our body handles glucose,” explained Dr. Bhandari, who has studied transplant patients who develop diabetes. “Muscle is one of the most important endocrine systems in our bodies.”
“Muscle loss,” added Dr. Armenian, “is the canary in the coal mine. A multi-organ hit is taking place, impacting metabolic health.”
Dr. Armenian’s research also revealed that losing muscle can affect the heart, as explained in a 2022 study on the subject: Transplant “survivors who have sarcopenia [muscle loss] have twice the risk of non-relapse mortality as compared to survivors without sarcopenia, which may be mediated in part by an excess incidence of premature cardiovascular disease.”
Viviana’s ALL Diagnosis at 18
No one had to explain those risks to Viviana Bivian, a 26-year-old graduate student studying film, graphic design, marketing and sports entertainment. At 18, Bivian suddenly experienced shortness of breath, dizziness and an inability to focus. Her doctors said she had a cold. Bivian looked further, and in short order a local hospital clinic diagnosed acute lymphoblastic leukemia.
“I was crying with the nurses,” she remembered. “I was just a kid, and I was panicking.”
Her medical team referred Bivian to City of Hope, where she immediately began chemotherapy and just as quickly reacted badly to it. “I had a horrible reaction. My body was shutting down. They sent me to intensive care and had to put me in a coma to treat me,” she recalled. A virus was consuming sections of Bivian’s skin and muscle and had to be arrested.
After months in the ICU, it was clear that a stem cell transplant was Bivian’s best option. Her father proved to be a compatible match, and a few weeks later Bivian had the procedure, but not before enduring intense side effects from the preparatory chemotherapy. “I couldn’t eat. I lost a lot of weight and a lot of muscle,” she said.
Her troubles continued post-transplant. In her weakened immune state, an injection caused an infection that led to necrotizing faciitis, commonly referred to as "flesh-eating disease." "Infections are common during the transplant process, when the patient is immunocompromised," said hematologist-oncologist Ibrahim T. Aldoss, M.D., associate professor in the Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, who treated Bivian. "However, hers was very severe and she was very critical." Bivian's right arm had to be amputated to save her life. This setback added to her overall weakness, which at times seemed like a bottomless pit.
“I’d lost my ability to walk,” she recalled. “I didn’t think I’d ever get it back.”
It is for patients like Bivian that Drs. Armenian and Bhandari are conducting a unique trial aimed at reversing muscle loss in young transplant patients. With their counterparts at Children’s Hospital Philadelphia and St. Jude’s Children’s Research Center in Memphis, Tennessee, they are testing an individually tailored program of exercise plus the nutritional supplement nicotinamide riboside, an over-the-counter, well-tolerated and easily absorbed vitamin B3 derivative that may improve muscle health.
The program is called IAMFIT (more formally, Intensive tailored exercise training with NAD+ precursor supplementation to improve muscle mass and fitness in adolescent and young adult hematopoietic cell transplant survivors). It’s a blind trial with 80 participants, ages 10 to 30, divided into four groups: One gets the exercise program plus the supplement. Another gets the exercise and a placebo. A third group will receive the supplement without the exercise plan, and the fourth will also receive no exercise training and take a placebo.
Researchers consider exercise to be so important that those in the non-exercise groups will be offered the fitness plan later, after they complete the trial.
Participants receive a stationary bike, free weights and a tablet computer for communicating with a trainer and tracking progress.
All the training happens remotely, in participants’ homes, after an in-person evaluation to establish benchmark fitness levels. Then, three times a week for 16 weeks, the St. Jude’s-based exercise physiologists in Memphis do a one-hour video session with each patient, putting them through a series of aerobic and strength exercises.
“I assess their needs and see what they need to work on,” explained Genevieve Lambert, one of 10 trainers in the program. “The exercises are specific for each patient and what they want. Week by week, we’ll vary the intensity. And I try to make sure that, at the end, they’re thinking about next steps. It helps them feel empowered in their own recovery. It helps them with the next stage of their lives.”
It is hoped that this trial will produce important data on exercise and supplements and also provide future patients with a clear, easy-to-follow plan they can use into their recovery and beyond.
Bivian went through the program in mid-2023. Her trainer adapted the exercises so Bivian could do them despite having lost her right arm. She feels good about the results.
Before the program, “I was afraid of even trying to exercise, worried I might break an arm or a leg,” she said. “But this program showed me I really can come back, and not be scared.”
Dr. Bhandari says participants are happy to see a potential path back to normal activity.
“We’re at such an exciting place,” she said. “We’re finding meaningful interventions that will make a difference in the lives of our patients.”