Shortly after giving birth to her first child, a 32-year-old woman began experiencing swelling in her feet and hands, extreme fatigue, and occasional leg paralysis. The skin on her hands tightened; simple movements became painful. She was not able to hold a bottle to feed her infant son. A competitive athlete, she was frightened by the sudden inflammation.
She consulted first with a holistic health practitioner, experimenting with dietary changes, detoxification, and vitamin infusions. The symptoms worsened. She consulted a rheumatologist who diagnosed systemic sclerosis (also known as scleroderma). Initial treatments of steroids and immunosuppressants proved ineffective. She was referred to a regional academic medical center where a specialist progressive, diffuse systemic sclerosis (SSc).
Because of the advanced disease progression, the woman was encouraged to consider hematopoietic stem cell transplantation (HSCT). Personal research led her to Duke Health’s novel collaboration between oncology and rheumatology; Duke is currently one of only a few centers nationally offering HSCT as a therapy for SSc.
Question: The Duke specialists who manage the HSCT program require that patients with SSc meet specific criteria to be considered for stem cell therapy. Would the patient qualify?
Answer: The patient was accepted for the novel therapy following an assessment and became one of the first patients to receive stem cell transplants at Duke for SSc since completion of the SCOT trial. Globally, approximately 600 procedures have been completed.
Ankoor Shah, MD, a rheumatologist who directs one of the Southeast’s only scleroderma clinics, works with Gwynn D. Long, MD, a cell therapy and hematologic malignancy specialist, to review several key health factors before accepting patients for the stem cell therapy. About 75% of referred patients are felt to be appropriate for the Duke program.
Duke has been deeply involved in the development of the HSCT therapy for treatment of SSc. Keith Sullivan, MD, from the Division of Hematologic Malignancies and Cellular Therapy at Duke, was a study chair in the long-running Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial that demonstrated the safety, efficacy and superiority of HSCT for systemic sclerosis compared to conventional immunosuppressive therapy.
By proving the efficacy of HSCT, the SCOT trial results were influential in convincing the insurance industry to begin coverage for the procedure.
“All the patients we consider for HSCT have typically tried several immunotherapies, including such drugs as methotrexate, mycophenolate mofetil and cyclophosphamide. These patients are viewed, in essence, as refractory to treatment,” says Shah. Other conditions that are considered:
- Early disease presentation of less than five years with rapidly progressive skin manifestations of scleroderma. The condition may also be causing joint paint, tendon involvement, generalized muscle and joint pain, and muscle contractions.
- Lung disease or a history of kidney disease. However, this patient’s disease had not yet affected her lungs or kidneys.
Acceptance into the Duke program requires that patients consult a financial counselor and social worker in addition to medical specialists to prepare for a comprehensive seven-week treatment program. The patient must relocate to Durham for the duration. Family members or a designated caregiver must be involved.
Treatment Process
The patient undergoes treatment with granulocyte colony-stimulating factor to prompt the bone marrow to produce stem cells and release them into the bloodstream so the cells can be collected. “This process also requires that we purify the patient’s stem cells, so we work closely with the stem cell processing lab to ensure that they have the supplies and the reagents and the manpower to complete the purification,” Long says.
The preparatory process requires the use of total body irradiation plus chemotherapy and other drugs to suppress the immune system. “Administering the radiation therapy is very complex,” Long says. Nicole A. Larrier, MD, MS, was the radiation oncologist for this procedure. The individuals involved in transplant work closely with the radiation oncology team to plan the radiation timing.
The body’s white cell count drops to zero, Long says, creating a vulnerable period in which the body lacks a functioning immune system and the risk of illness is extremely high. The blood counts recover over a period of two to three weeks, but the immune system can take several weeks to recover to a point at which patients can safely return home.
The Outcome
The patient, who underwent HSCT at Duke early in 2019, has experienced a dramatic medical recovery. No longer dealing with near-constant pain and exhaustion, she has returned to work and is balancing a career as a mother and a professional. Because of the extreme skin presentation, the longest and most difficult part of the patient’s recovery was the slow restoration of her prior skin condition.
Neither Long nor Shah will use the term “cure” to describe outcomes for patients with immunotherapy diseases, but they say this patient has experienced among the most complete recoveries.
“It’s important to follow demographic data and identify the true window of benefit for patients in terms of their disease progression and baseline characteristics,” Shah says. “The best outcomes occur in patients with early aggressive systemic sclerosis. This patient was an example.”
